Iaoe?iiaeueia aeaaeai?y iaoe Oe?a?ie

?inoeooo aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia??

?i. ?.?. Eaaaoeueeiai

I?i?noa?noai ioi?iie caei?ia’y Oe?a?ie

Oe?a?inueeee iaoeiai-aeine?aeiee ?inoeooo iieieia?? oa ?aae?ieia??

Neaei?aiei Na?oeaia Iaae?aia

OAeE: 616-006[.441+.446]:616-097

IIA? IIAA?OIAA? AIOEAAIE EE?OEI, UI

AEssAEssTHOUeNss IIIIEEIIAEUeIEIE AIOEO?EAIE NA??? ?II,

I?E EAEEICAO OA E?IOIIAO

14.01.07 — iieieia?y

AAOI?AOA?AO

aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

aeieoi?a a?ieia?/ieo iaoe

Ee?a — 1998

Aeena?oaoe??th ? ?oeiien

?iaioa aeeiiaia a ?inoeooo? aenia?eiaioaeueii? iaoieia??, iieieia?? ?
?aae?ia?ieia?? ?i. ?.?. Eaaaoeueeiai IAI Oe?a?ie.

Iaoeiaee eiinoeueoaio — aeieoi? iaaee/ieo iaoe, i?ioani?

Aeociai Aeaieei O?oaeaae/,

caa?aeoaa/ a?aeae?eo ?ioiioeeoio?i??

?inoeoooo aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i.
?.?. Eaaaoeueeiai IAI Oe?a?ie

Io?oe?ei? iiiiaioe: — /eai-ei?aniiiaeaio IAI Oe?a?ie,

aeieoi? a?ieia?/ieo iaoe, i?ioani?

Aey/aiei Iaoae?y Na?a??aia,

caa. a?aeae?eii iieaeoey?ii? a?ieia?? a??on?a ?inoeoooo i?e?ia?ieia?? oa
a??onieia??

?i. Ae.E. Caaieioiiai IAI Oe?a?ie

— aeieoi? a?ieia?/ieo iaoe

Ni??iiaa ??eia Aiae??yi?aia, i?ia?aeiee iaoeiaee ni?a?ia?oiee a?aeae?eo
iieaeoey?ieo iaoai?ci?a eaeeiciaaiaco ?inoeoooo aenia?eiaioaeueii?
iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i. ?.?.Eaaaoeueeiai IAI Oe?a?ie

— aeieoi? a?ieia?/ieo iaoe, i?ioani?

Iico? Aieiaeeie? Einoyioeiiae/,

i?ioani? eaoaae?e i?e?ia?ieia?? oa ?ioiieia?? Ee?anueeiai oi?aa?neoaoo
?iai? Oa?ana Oaa/aiea

I?ia?aeia onoaiiaa — Iaoeiaee oeaio? ?aae?aoe?eii?
iaaeeoeeie AII Oe?a?ie,

?inoeooo ee?i?/ii? ?aae?ieia??,

a?aeae?e ?ioiieia??, i. Ee?a

Caoeno a?aeaoaeaoueny “_23_” a?oaeiy 1998 ?. i 13.30.

ia can?aeaii? niaoe?ae?ciaaii? a/aii? ?aaee Ae 26.155.01 a ?inoeooo?
aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i. ?.?.
Eaaaoeueeiai IAI Oe?a?ie (252022, Ee?a-22, aoe. Aaneeuee?anueea, 45).

C aeena?oaoe??th iiaeia iciaeiieoenue o a?ae?ioaoe? ?inoeoooo
aenia?eiaioaeue-ii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i. ?.?.
Eaaaoeueeiai IAI Oe?a?ie

Aaoi?aoa?ao ?ic?neaiee “_19_” eenoiiaaea 1998 ?.

A/aiee nae?aoa?

niaoe?ae?ciaaii? a/aii? ?aaee

aeieoi? iaaee/ieo iaoe ?.A. Aa?aiaiei

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE.

Aeooaeuei?noue i?iaeaie. A?eueo?noue e?ioi?aeieo oi?i eaeeic?a oa e?ioii
ethaeeie — oea ceiye?ni? iiaiooai?aiiy A-ee?oeiiiai iioiaeaeaiiy. Aiie
aeeth/athoue A-ee?oeii? aa??aioe aino?iai e?ioiaeanoiiai eaeeico (AEE),
o?ii?/iee e?ioieaeeic (OEE), ??ciiiai?oi? oeeoieia?/i? aa??aioe
A-ee?oeiieo iaaiaeaee?inueeeo ceiye?nieo e?ioii (ICE), aieinaoiee?oeiiee
eaeeic (AEE) oa i??eiiio oai?iao (IO) (Foon K.A. et al., 1988;
Aa?uoieeia A.TH. e ae?., 1989; Iei/oe A.A. e ae?., 1990; Greaves M.F.,
1997; Stein H., 1997). Ee?oeiaie, ui caciathoue ceiye?nio
o?ainoi?iaoe?th, cae/aeii noathoue iaaeeoa?aioe?eiaai?
ee?oeie-iiia?aaeieee, a yeeo i?ioeane i?ie?oa?aoe?? iia’ycai? c
?aa?aiaeoaaiiyi aai?a. Ia oeeo noaae?yo aeeoa?aioe?thaaiiy aeieeathoue
aaiiii? ii?ooaiiy, ye? /anoi i?iyaeythoueny o ?aa?aiaeoaaii? i?ae
eieonaie aai?a ?ioiiaeiaoe?i?a oa i?ioi-iieiaai?a, oei naiei ii?oooth/e
i?ioeane i?ie?oa?aoe?? oa aeeoa?aioe?thaaiiy (Aooaiei C.A., 1988, 1995;
Kipps T., 1993; Korsmeyer S.J., 1988, 1995; Evan G., Littlewood T.,
1998). Aiane?aeie oeueiai ??ci? oeeoieia?/i? aa??aioe A-ee?oeiieo
eaeeic?a oa e?ioii oa?aeoa?ecothoueny iaeiie/aiiyi iaoieia?/ieo
A-ee?oei, aeie aeeoa?aioe?thaaiiy yeeo aeiee ia ie?aieo niaoeeo?/ieo
noaae?yo aeic??aaiiy (Pinto A. et al., 1994; Foon, 1995; Ghia, Nadler,
1997). Oiio aea/aiiy ee?oeiieo oa iieaeoey?ieo ia?ea??a, anioe?eiaaieo c
??ciiiai?oieie noaae?yie aeeoa?aioe?thaaiiy e?ioioeeo?a, ? eeth/iaei
iiiaioii aeey ?icoi?iiy eeiiaeueii? i?ie?oa?aoe?? ceiye?nieo ee?oei oa
?ic?iaee i?aeoiae?a aei ae?aaiinoeee, eeaneo?eaoe?? ? oa?ai?? eaeeic?a
oa e?ioii.

Ia ii/aoeo 70-o ?ie?a ?ioiieia?/i? iaoiaee ii/aee aeiiiaithaaoe
eeane/i? ii?oieia?/i? oa oeeoio?i?/i? i?aeoiaee o aea/aii? noaae?e
aeeoa?aioe?thaaiiy e?ioioeeo?a, ae?aaiinoeoe? oa eeaneo?eaoe?? eaeeic?a
oa e?ioii. Ai?iaaaeaeaiiy aaoa?iaioene?iaaoie oa ?aaeoe??
?icaoeiooai?aiiy a?aee?eei iia? ia?niaeoeae aeey eaeeicieia?? oa caeeaei
iniiae ?ioiioaiioeioaaiiy e?ioi?aeieo ee?oei a ii?i? ? i?e iaoieia??
(Aeociai Ae.O., 1978; Aeociai Ae.O. e ae?. 1982; Iei/oe A.A. e ae?.,
1990).

?ic?iaea a?a?eaeiiii? oaoiieia?? io?eiaiiy iiiieeiiaeueieo aioeo?e
(IEAO) o 1975 ?ioe? (Kohler G., Milstein C., 1975) ?icii/aea iiaee aoai
o ?icaeoeo a?ieia??. A/ai? io?eiaee oi?eaeueiee ?ino?oiaio, ca
aeiiiiiaith yeiai iiaeia iai?ioethaaoe ie?aieie iieaeoeaie ?, iaa?oue,
ie?aieie aioeaaiieie aeaoa?i?iaioaie, ye? ?ici?ciathoueny IEAO. Oea
noaei neeueiei noeioeii aei ?icaeoeo iieiaaiaoieia?? ? iniaeeai
?aeaioeo?eaoe?? oa ?ioiioaiioeioaaiiy iaoieia?/ieo ee?oei i?e ??cieo
oeeoieia?/ieo aa??aioao eaeeic?a oa e?ioii ethaeeie (Oeeaoia A.A. e ae?.
1989; Eaaeaaeaeca C.A., 1990; Aa?uoieeia A.TH. e ae?., 1998; Eeeiiae/
A.A., 1998).

Iiooe iiaeo aioeaai?a e?ioioeeo?a, aea/aiiy ?o aeni?an?? oa ooieoe?e,
noai?aiiy iaiaeae IEAO aeey ?ioiioaiioeioaaiiy e?ioioeeo?a ? iaeiei c
aieiaieo iai?yie?a ?icaeoeo iieiaaiaoieia?? oa neeaaea? iniiao no/anii?
aeeoa?aioe?aeueii? ae?aaiinoeee, eeaneo?eaoe?? oa ?ioiioa?ai??
e?ioi?aeieo oi?i eaeeic?a oa e?ioii ethaeeie. Oe? caaaeaiiy aoee
iinoaaeai? a i?ia?aiao AeEIO Oe?a?ie oa I?i?noa?noaa Oe?a?ie o ni?aaao
iaoee ? oaoiieia?e, ieaiao iaoeiai-aeine?aeieo ?ia?o ?inoeoooo
aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i. ?.?.
Eaaaoeueeiai IAI Oe?a?ie 0.69.05.02.01 Ae(n), oa 0194UO17021, oeo?
i?iaeaie 2.28.2.8, a oaeiae a i?aeia?iaeieo a?aioao Aia?eeainueeiai
i?ioe?aeiaiai oiaa?enoaa (ACS) ? Iaaee/iiai ?inoeoooo ?i. Aiaa?aea
O’thca (HHMI a?aio 75195-548101).

Iaoa ? caaea/? aeine?aeaeaiiy. Iaoa ?iaioe iieyaaea o ?ic?iaoe? iiaeo
i?aeoiae?a aei i?aeaeuaiiy aoaeoeaiino? ?ioiioaiioeioaaiiy e?ioi?aeieo
ee?oei ? aeeoa?aioe?aeueii? ae?aaiinoeee, eeaneo?eaoe?? oa ?ioiioa?ai??
eaeeic?a oa e?ioii ethaeeie ia iniia? aea/aiiy iiaeo aioeaai?a
aeeoa?aioe?thaaiiy A-e?ioioeeo?a ethaeeie.

Aei caaea/ aeine?aeaeaiiy aoiaeeei:

1. Oo?eiaoe iaiaeue IEAO aei aioeaai?a aeeoa?aioe?thaaiiy e?ioioeeo?a
ethaeeie aeey aeei?enoaiiy a iieiaaiaoieia?/ieo aeine?aeaeaiiyo.

2. Aea/eoe niaoeeo?/i?noue io?eiaieo IEAO ia ??cieo ee?oeiao-i?oaiyo, ui
aeeth/athoue e?i?? ee?oei ??ciiai iioiaeaeaiiy, ee?oeie e?ia? ?
e?iaioai?ieo i?aai?a a ii?i? oa i?e ??cieo oeeoieia?/ieo aa??aioao
eaeeic?a oa e?ioii ethaeeie.

3. C’ynoaaoe aeeiai?eo aeni?an?? aioeaai?a, ui aeyaeythoueny ca
aeiiiiiaith IEAO na??? ?II (?inoeooo i?iaeai iieieia??) i?e aeoeaaoe??
oa aeeoa?aioe?thaaii? e?ioioeeo?a.

4. I?iaanoe a?io?i?/iee aiae?c aioeaai?a, ui ?ici?ciathoueny IEAO na???
?II, c iaoith ?o ?aeaioeo?eaoe?? oa eeanoa?oaaiiy c IEAO aei a?aeiieo
iieaeoe.

5. Aecia/eoe ooieoe?? aioeaai?a, ui aeyaeythoueny IEAO na??? ?II.

6. ?ic?iaeoe i?aeoiaee oa ?aeiiaiaeaoe?? aeey ?ioiioaiioeioaaiiy
iaoieia?/ieo A-ee?oei i?e AEE, OEE, AEE, ICE oa IO.

Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a.

Aeyaeaii 2 iiaeo iiaa?oiaaeo aioeaaie CD95 oa CDw150. Noai?aii ia?oo
a?o/eciyio iaiaeue IEAO aei aioeaai?a aeeoa?aioe?thaaiiy e?ioioeeo?a
ethaeeie. Aia?oa iaea?aeai? IEAO ?II-3 i?ioe iiaiai aioeaaia CDw150.
Becia/aia aeni?an?y, no?oeoo?a oa ooieoe?? oeueiai aioeaaia (AA).
?aeaioeo?eiaai? iieaeoee, ui anioe?eiaai? c CDw150, oa iieacaia ?ieue
oeueiai AA o ?aaoeyoe?? aeeoa?aioe?thaaiiy oa cai?ia?aiiaaii? nia?o?
ee?oei, aai aiiioico.

Aia?oa io?eiai? IEAO ?II-4 aei aeoeaaoe?eiiai AA ND95, ui iaae?th?
aiiioic. Aea/aia aeni?an?y oeueiai aioeaaia a ii?i? ? i?e e?ioi?aeieo
oi?iao eaeeic?a oa e?ioii, a oaeiae ioa?aeoa?eciaai? ooieoe?iiaeuei?
iniaeeaino? ND95. Ciaeaeaii, ui neaiae /a?ac CD40 iiaeoeth?
CD95-iiina?aaeeiaaiee aiiioic a A-ee?oeiao a ii?i? oa i?e OEE.

Iieacaii, ui IEAO ?II-10 ?ici?ciathoue iie?ii?oio aeaoa?i?iaioo HLA-DR
oa iathoue aaaeeeaa cia/aiiy aeey aeeoa?aioe?aeueii? ae?aaiinoeee AEE
A-ee?oeiiiai iioiaeaeaiiy, i?aeaa??aio?a OEE oa aenieiaeeoa?aioe?eiaaieo
ICE.

Aeiaaaeaii, ui IEAO ?II-24 aeyaeythoue ND37 aioeaai, oa ioa?aeoa?eciaaia
aeni?an?y oeueiai AA a ii?i?, i?e aeoeaaoe?? A-e?ioioeeo?a, a oaeiae i?e
??cieo oeeoieia?/ieo aa??aioao e?ioi?aeieo oi?i eaeeic?a ? e?ioii
ethaeeie.

Ca aeiiiiiaith IEAO na??? ?II aeae?eai? i?aeaa??aioe A-I AEE oa
A-ee?oeiiiai OEE, ui a?ae??ciythoueny ca ??aiai aeeoa?aioe?thaaiiy
iaoieia?/ieo ee?oei, anoaiiaeai? oaiioei?/i? iniaeeaino? iooeeiieo
ee?oei i?e AEE oa aenieiaeeoa?aioe?eiaaieo ICE.

I?aeoe/ia cia/aiiy iaea?aeaieo ?acoeueoao?a. Ia iniia? ?acoeueoao?a
aea/aiiy aeni?an?? aioeaai?a, ui aeyaeythoueny ca aeiiiiiaith IEAO na???
?II, iiiieeiiaeuei? aioeo?ea ?II-3, ?II-4, ?II-10 oa ?II-24
cai?iiiiiaai? aeey ?ioiioaiioeioaaiiy, ae?aaiinoeee, eeaneo?eaoe?? oa
?ioiioa?ai?? e?ioi?aeieo oi?i eaeeic?a oa e?ioii ethaeeie. Oey iaiaeue
IEAO oe?iei aeei?enoiao?oueny aeey ?ioiioaiioeioaaiiy A-e?ioioeeo?a
ethaeeie a ii?i? ? i?e iaoieia?? a 67 iaoeiai-aeine?aeieo oa i?aeoe/ieo
caeeaaeao Oe?a?ie, ?in??, A?ei?on??, Eaoa??, Eeoae, Anoii??, A?oc??,
?anioae?ee Eoaa, Aieeaiae??, Aaeeeia?eoai?? oa NOA. I?ae ea??aieoeoaii
aaoi?a i?eioeeiaie oa iaoiaeaie canoinoaaiiy IEAO na??? ?II aeey
?ioiioaiioeioaaiiy e?ioioeeo?a iaieiae?ee iaoeia? i?aoe?aieee oa
e?ea??-eaai?aioe ?ioiieia?/ieo eaai?aoi??e c 18 iaoeiaeo oa i?aeoe/ieo
caeeaae?a Oe?a?ie, ?in?enueei? Oaaea?aoe??, A?ei?on??, Eaoa??, Eeoae,
Anoii?? oa A?oc??.

Iniaenoee aianie caeiaoaa/a. Aeena?oaioo iaeaaeeoue ?aeay io?eiaiiy
iaiae? IEAO na??? ?II aei aioeaai?a aeeoa?aioe?thaaiiy A-ee?oei
ethaeeie. Aiia aaciina?aaeiuei i?eeiaea o/anoue a io?eiaii? a?a?eaeii,
ui nae?aoothoue IEAO na??? ?II, a oaeiae o aea/aii? niaoeeo?/iino? oeeo
IEAO. Iath naiino?eii i?iaaaeai? a?io?i?/i?, ?ioiio?i?/i? oa
ooieoe?iiaeuei? aeine?aeaeaiiy aioeaai?a, ui ?ici?ciathoueny IEAO na???
?II. Naiino?eii aiae?coaaea aanue io?eiaiee iaoa??ae, oi?ioethaaea an?
iieiaeaiiy oa aeniiaee ?iaioe. Aiooaaea aei ae?oeo a?eueo?noue iaoeiaeo
?ia?o, a yeeo a?aeia?aaeai? ?acoeueoaoe aeena?oaoe??.

Ai?iaaoe?y ?iaioe. Iaoa??aee ?iaioe aoee i?aaenoaaeai? oa iaaiai?ai? ia
Ananithcieo eiioa?aioe?yo “Nia?aiaiiua iaoiaeu nicaeaiey iaaeeoeeineeo
aeeaaiinoeeoiia” (Iineaa, 1988, 1990), “Aeooaeueiua aii?inu aeeaaiinoeee
caaieaaaiee nenoaiu e?iae” (Noooi?, 1988), “Aeooaeueiua aii?inu a
aeioeie/aneie e eiioiieiae/aneie aeeaaiinoeea ceiea/anoaaiiuo
iiaiia?aciaaiee” (Iineaa, 1989), ?anioae?eainuee?e eiioa?aioe??
“Iaoai?cie eaioea?i- ? eaeeiciaaiaco» (Ee?a, 1990), ?iai/eo
eiioa?aioe?yo e?a?i-/eai?a ?AA ii i?iaeai? “?ioiieia?y iooeei” (Iineaa,
1987; ?eaa, 1990), I?aeia?iaeieo eiioa?aioe?yo “Tumor Markers” (Ee?a,
1990), “Oncodevelopmental Biology and Medicine” (Iineaa, 1990), “FASEB”
(Aiaoaei, NOA, 1992); “V International Workshop and Conference on Human
Leucocyte Differentiation Antigens” (Ainoii, NOA, 1993); “ 9th
International Congress of Immunology” (Nai-O?aioe?nei, NOA, 1995); “VI
International Workshop and Conference on Human Leucocyte Differentiation
Antigens” (Eiaa, ssiii?y. 1996), Conferences of Howard Hughes Medical
Institute (I?aaa, 1996, Aa?oaaa, 1997 oa Aoaeaiaoo, 1998), “13th
European Immunology Meeting”(Ainoa?aeai, 1997), “8th European Congress
on Biotechnology” (Aoaeaiaoo, 1997), “17th International Cancer
Congress” (??i aea AEaiae?i, A?ac?e?y, 1998).

Ioae?eaoe??. Iniiaiee ci?no aeena?oaoe?eii? ?iaioe aeeeaaeaiee o 60
ioae?eaoe?yo, a oiio /ene? a 4 aaoi?nueeeo na?aeioeoaao, 1 iiiia?ao?? oa
35 aeo?iaeueieo noaooyo.

No?oeoo?a oa ianya aeena?oaoe??. Aeena?oaoe?y neeaaea?oueny ?c anooio,
iaeyaeo e?oa?aoo?e (o?e i?ae?icae?ee), oanoe ?icae?e?a aeanieo
aeine?aeaeaiue, aiae?co oa ocaaaeueiaiiy ?acoeueoao?a aeine?aeaeaiue,
aeniiae?a ? nieneo oeeoiaaii? e?oa?aoo?e. Aeena?oaoe?y aeeeaaeaia ia 287
noi??ieao iaoeiiieno oa i?noeoue 27 oaaeeoeue ? 54 ?enoiea. Nienie
aeei?enoaieo aeaea?ae aeeth/a? 291 iaeiaioaaiiy, c ieo 27 — ia
oe?a?inuee?e oa ?in?enuee?e iiaao, 264 — ia aiae?enuee?e iia?.

IAOA??AEE OA IAOIAeE AeINE?AeAEAIUe

A?a?eaeiie, ui nae?aoothoue iiiieeiiaeuei? aioeo?ea ?II-3 (IgG1), ?II-4
(IgM), ?II-10 (IgG3) oa ?II-24 (IgG2b), aoee io?eiai? a ?acoeueoao?
niiaoe/ii? a?a?eaeecaoe?? nieaiioeeo?a ieoae e?i?? BALB/c c ee?oeiaie
ieoeii? i??eiie P3-X63.Ag8.653 oa o aeiaaeeo IEAO ?II-24 — 653A
noae?i??, ui aoea etha’ycii iaaeaia ae?. A.A. Eeeiiae/ai (?in?y). Aoei
aeei?enoaii o?e aa??aioe aeiaaino?ieiai? ?ioi?caoe?? c aeei?enoaiiyi
A-e?ioiaeanoi?aeii? e?i?? ee?oei RPMI-1788 (IEAO ?II-3 oa ?II-4),
A-ee?oeiii? e?i?? Daudi (IEAO ?II-10) oa ee?oei naeac?iee oai?iai ia AEE
(IEAO ?II-24). *a?ac /ioe?e aeiae ii cae?i/aiith ?ioi?caoe?? i?iaiaeeee
a?a?eaeecaoe?th ee?oei naeac?iee c ee?oeiaie i??eiie ca aeiiiiiaith 50%
iie?aoeeaiae?eieth c i.i. 2000 Ae ca iaoiaeii Davidson R. oa Gerald P.
[1978]. I?ney naeaeoe?? ee?oeiieo a?a?eae?a o AAO ? AO na?aaeiaeuao
i?iaiaeeee ne?ei?ia i?iaeoeoe?? niaoeeo?/ieo aioeo?e, aeei?enoiaoth/e
iaoiae ?ioiioeoi?anoeaioe?? o iai?yiiio aa??aio? ia iiiioa?? aeeaeo
ee?oei. I?ney eeiioaaiiy, ?aeeiioaaiiy ? eoeueoeaoaaiiy in vitro aoee
a?ae?a?ai? eeiie a?a?eaeii, ye? aeoeaii i?iaeoeothoue aioeo?ea aei
iiaa?oiaaeo aioeaai?a ee?oei e?i?e RPMI-1788, Daudi, /e naeac?iee
oai?iai ia AEE. A?a?eaeiie, ui nae?aoothoue IEAO ?II-3 oa ?II-10, aoee
io?eiai? oa ioa?aeoa?eciaai? o ni?a?ia?oieoeoa? c e.i.i. I.I. A?o?iaith,
a a?a?eaeiie, ui nae?aoothoue IEAO ?II-4 oa ?II-24 — o ni?a?ia?oieoeoa?
c e.i.i. I.I. A?o?iaith, e.a.i. E.I. Oeaiaoeueeith oa e.a.i. A.A.
Aa?aeiaith. An? a?a??aeiie caoeuai? aaoi?nueeeie na?aeioeoaaie: N
1389284 (?II-3), N 1420020 (?II-10), N 1684338 (?II-4) oa N 1705343
(?II-24).

A ?iaio? aoea aeei?enoaia aaeeea iaiaeue IEAO oa ne?iaaoie, ui aoee
io?eiai? a?ae eieaa, Aia?eeainueei? eieaeoe?? eoeueoo? ee?oei (AONN),
IV, V oa VI I?aeia?iaeieo ?iai/eo aeine?aeaeaiue aioeaai?a
aeeoa?aioe?thaaiiy eaeeioeeo?a oa o??ie DAKO (Aeai?y). Oey iaiaeue
aeeth/aea IEAO aei ND1, ND2, ND3, ND5, ND38, HLA-DR (i?io. A.TH.
Aa?eoi?eia, ?in?y); ND4, ND7, ND8, ND21 (ae?. A.A. O?eaoia, ?in?y); L oa
H eaioetha?a Ig (ae?. A.A. Eeeiiae/, ?in?y); ND10, ND19, ND21, ND22,
ND23, ND25, ND30, ND37, ND45, (DAKO, Aeai?y), a oaeiae IEAO HD37
aioe-ND19 (ae?. T. Pezzutto, I?ia//eia), 1F5 aioe-ND20, G19-4 aioe-ND3
(ae?. J. Ledbetter, NOA), MOPC21, W6/32 aioe-HLA-I eeano oa IA10 aioe-
HLA-DR (ATCC); G28-1 aioe-ND37, G28-5 aioe-ND40, G28-10 aioe-ND39,
G28-8 aioe-Bgp95, LB-2 aioe-ND54, AA-1 aioe-ND80, LB-1, 2N3 aioe-IgM
(ae?. E.A. Clark, NOA), BLAST2 oa III6 aioe-CD23, AD-2 aioe-ND73, LN1
aioe-ND75, 424/4A11 ? 424/3D9 aioe-NA77, B5, HN2, BLAST1, L22, oa ?io?
(IV, V oa VI I?aeia?iaei? ?iai/? aeine?aeaeaiiy aioeaai?a
aeeoa?aioe?thaaiiy eaeeioeeo?a). Aaoa?iaioene?iaaoee oa IEAO aei
eiiiiiaio?a neaiaeueieo eaneaae?a aoee i?eaeaai? o a?ioaoiieia?/ieo
eiiiai?e: Santa Cruz Biotechnology, UBI, Transduction Laboratories oa
Jackson (NOA).

Aeine?aeaeaiiy i?iaiaeeee ia 28 e?i?yo ee?oei ethaeeie, ui aeeth/aee
e?i?? ee?oei A-e?ioioeeoa?iiai iioiaeaeaiiy: RPMI-1788, PHS, T5-1, 6.16,
DB, CESS, MP-1, Raji, Ramos, Daudi, EB-3, Namalwa, REH, Nalm-6,
RPMI-8226 oa HCLL-7876; O-ee?oeii? e?i??: CEM, MOLT-4, CCRF-HSB2, MT-4,
HUT, H9, HPB-ALL, Jurkat, a oaeiae ee?oeii? e?i?? iae?ioi?aeiiai
iioiaeaeaiiy: E-562, U-937, A-431, Mewo. Oe? ee?oeii? e?i?? aoee
etha’ycii iaaeai? eieaeoe??th ee?oeiieo e?i?e ?inoeoooo Oeeoieia?? AI
?in??, AONN, i?io. I.A. ?ioe?iei, i?io. A.?. Aaae?aei, i?io. A.TH.
Aa?eoi?eiaei ? i?io. E.A. Clark. Ee?oeie eoeueoeaoaaee o na?aaeiaeu?
RPMI-1640 c aeiaeaaaiiyi 10% aia??iiaeueii? oaey/i? ne?iaaoee oa
noaiaea?oieo aeiaeaoe?a.

A ?iaio? oaeiae aoee aeei?enoai? iiiiioeeaa?i? ee?oeie ia?eoa??eii?
e?ia?, ieaaeaeee?a, naeac?iee, oeiono, e?ioaoe/ieo aoce?a, e?noeiaiai
iicieo 156 i?aeoe/ii caei?iaeo in?a oa 170 oai?eo ia eaeeice oa e?ioiie,
ui aeeth/aee o?ii?/iee e?ioieaeeic (46), aino?ee e?ioiaeanoiee eaeeic
(27), aino?ee i??eiaeanoiee eaeeic (11), aieinaoiee?oeiiee eaeeic (8),
iaaiaeaee?inuee? ceiye?ni? e?ioiie (34), e?ioia?aioeaiaoic (36) oa
i??eiiio oai?iao (8). Oai?? ciaoiaeeeenue ia e?eoaaii? o aaiaoieia?/ieo
a?aeae?eaiiyo 25-? ee?i?/ii? e?ea?i?, Ee?anueei? iaeanii? e?ea?i? oa
14-? aeeoy/i? niaoe?ae?ciaaii? e?ea?i? i.Ee?aa. Ae?aaiice eaeeic?a oa
e?ioii aoee iinoaaeai? ia iniia? noaiaea?oieo ii?oieia?/ieo, ee?i?/ieo
oa oeeoio?i?/ieo e?eoa???a o ni?a?ia?oieoeoa? c ae.i.i. E.I. Neey?aiei
oa e.a.i. A.A. Iaaeai?iith i?e eiinoeueoaoe?? ae.i.i., i?io. Ae.O.
Aeociaia. ?ioiia?noieia?/i? oa oeueo?ano?oeoo?i? aeine?aeaeaiiy
e??inoaoieo c??c?a e?ioaoe/ieo aoce?a i?iaaaeai? ?acii c e.a.i. I.A.
TH?/aiei. Ii?oieia?/iee, oeeoio?i?/iee oa oeueo?ano?oeoo?iee aiae?c
ee?oei i?iaiaeeee ca noaiaea?oieie iaoiaeeeaie (Aeociai Ae.O. e ae?.,
1982; Iei/oe A.A. e ae?., 1990).

Iiiiioeeaa?i? ee?oeie aeae?eyee c e?ia? oa e?iaioai?ieo i?aai?a a
a?aae??io? u?eueiino? o?eiee-aa?ia?ao?i (d=1,077 a/ni3), /e
aeei?enoiaoth/e Lymphoprep (Pharmacia, Oaaoe?y). O- ? A-ee?oeie
?icae?eyee i?ney ?aaeoe?? ?icaoeiooai?thaaiiy c a?eo?ioeeoaie aa?aia
(Clark E.A., Shu G., 1986), a A—ee?oeie ?icae?eyee ia o?aeoe?? ??cii?
u?eueiino? o a?aae??io? 60%, 55%, 50% oa 45% ia?eieeo (Pharmacia,
Oaaoe?y) (Clark E.A. et al., 1989).

I/euaiiy IEAO, eii’thaaoe?y c oeoi?anoea?i ?cio?ioe?aiaoii (O?OOe),
a?ioeiii (I-hydroxysuccinimidobiotin) oa NNBr-aeoeaiaaiith naoa?icith 4A
i?iaiaeeeeny ca noaiaea?oieie iaoiaeeeaie (Clark E.A. et al., 1986).
Iiaa?oiaa? oa oeeoiieaciaoe/i? AA ee?oei aeyaeyee ca aeiiiiiaith
ne?aeoth/eo ?ioiioeeoio?i?/ieo iaoiae?a: 1) Iai?yiee
?ioiioeoi?anoeaioiee iaoiae c aeei?enoaiiyi IEAO oa F(ab’)2 o?aaiaio?a
aoi?eiieo aioeo?e i?ioe ieoa/eo Ig, i?/aieo O?OOe (TAGO, NOA). 2)
Iai?yiee ?ioiioeoi?anoeaioiee iaoiae c aeei?enoaiiyi a?ioei?eueiaaieo
IEAO oa no?aioaa?aeeio, eii’thaiaaiiai c O?OOe, aai c o?eia?eo?eiii
(OA). 3) I?yiee ?ioiioeoi?anoeaioiee iaoiae c aeei?enoaiiyi IEAO,
eii’thaiaaieo c O?OOe, aai c OA. 4) Iai?yiee ?ioiioa?iaioiee iaoiae c
aeei?enoaiiyi IEAO oa aoi?eiieo aioeo?e, i?/aieo ia?ieneaeacith o?iio
(DAKO, Aeai?y). 5) Iai?yiee ?ioiioa?iaioiee iaoiae c aeei?enoaiiyi
a?ioei?eueiaaieo IEAO oa no?aioaa?aeeio, eii’thaiaaiiai c
ia?ieneaeacith o?iio (Sigma, NOA). 6) IAI-iaoiae
(ia?ieneaeaca-aioe-ia?ieneaeaca) c aeei?enoaiiyi IEAO, aoi?eiieo
e?iey/eo aioeo?e i?ioe Ig ieoae oa eiiieaeno IEAO i?ioe ia?ieneaeace c
ia?ieneaeacith o?iio (ae?. A.A. Eeeiiae/, ?in?y).

Oeoi?anoeaioiee aiae?c i?iaiaeeee ia iiiioa?? aeeaeo /e o?eniaaieo
ee?oei, ui i?ee??iethaaee aei i?aaeiaoieo neaeaoeue, ia?iaeaieo ?ic/eiii
iie?-L-e?ceio (Sigma, NOA), ? ioe?ithaaee ?aaeoe?th ca aeiiiiiaith
?ioiioeoi?anoeaioiiai i?e?ineiia. Oaeiae iaeii- oa aeaieieuei?iaee
aiae?c i?iaiaeeee ia i?ioi/iiio oeeoioeoi?eiao?? FACScan (Becton
Dickinson, NOA), aeei?enoiaoth/e iieaciee IO? (i?e oeoi?anoeaioii?
?ioaineaiino?), ui neeaaea? a?aeiioaiiy e?i?eieo oeoi?anoeaioieo
?ioaineaiinoae i?aia?aoo, ui aea/a?oueny, ? eiio?ieth (Clark E.A. et
al., 1989).

Ooieoe?iiaeuei? oanoe aeeth/aee: ioe?ieo i?ie?oa?aoeaii? aeoeaiino?
ee?oei, ci?ie ??aiy aioo?eee?oeiiiai Na2+ [Na2+]?, ?iaeoeoe?th oa
iiaeoeyoe?th cai?ia?aiiaaii? nia?o? ee?oei (aiiioico). Ee?oeie
eoeueoeaoaaee o eaaae?eie?eaoao c aeiaeaaaiiyi iaeiiai /e a?eueoa
noeioeyoi??a: aioeo?e i?ioe IgM, IL-4, ?IA, ??cieo i?oiaai?a oa IEAO.
I?ney eoeueoeaoaaiiy a?ae 30 oaeeei aei 7 ae?a ee?oeie cae?aee, aeyaeyee
ia ieo iiaa?oiaa? AA, ioe?ithaaee ??aaiue aiiioicieo ee?oei, aai
eoeueoeaoaaee 18 aiaeei c 0,5 ieN? [3H]-oei?aeeio ia eoieo.
?aae?iaeoeaii i?/ai? ee?oeie cae?aee ia o?eueo?e oa aei??thaaee
?aae?iaeoeai?noue o noeeioeeyoe?eiiio e?/eeueieeo (Becton Dickinson,
NOA). Aeey aei??thaaiiy ??aiy aioo?eee?oeiiiai [Na2+]? ee?oeie aoee
iane/ai? aoeaoien?iaoeeiaei ao??ii Indo-1 (Molecular Probes, NOA). Ci?ie
??aiy [Na2+]? aei??thaaee ca aeiiiiiaith i?ioi/ii? oeeoioeoi?eiao??? ia
FACSstar aiae?caoi?? (Becton Dickinson, NOA). Aeey ioe?iee ??aiy
aiiioicieo ee?oei a iiioeyoe?? ie aeei?enoiaoaaee /ioe?e iaoiaee
oa?aoaaiiy ee?oei: 1) aiiaen?i V, eii’thaiaaiee c O?OOe (Clonteck, NOA);
2) Hoechst 33342 (Sigma, NOA); 3) Propidium Iodide (Sigma, NOA); 4)
noaiaea?oi? ii?oieia?/i? oa oeeoio?i?/i? iaoiaeeee.

A ?iaio? aoee aeei?enoai? ne?aeoth/? a?io?i?/i? iaoiaee: ?aaeoe?y
?ioiii?aoeei?oaoe??, iaoaaie?/ia oa o?i?/ia i?/aiiy iiaa?oiaaeo
aioeaai?a ee?oei, aeaeo?ioi?ac o iie?ae??eai?aeiiio aae? c
aeiaeaoeeenoeueoaoii Na (AeAeN), Western aeioo?ia, e?iacia ?aaeoe?y in
vitro, oinoiai?iieeneioiee aiae?c, aeae?eaiiy noaee?oeiieo o?aeoe?e
oeyoii acioii? eaa?oaoe?? oa oeueo?aoeaio?eooaoaaiiy (Leprince C. et
al., 1992; Sidorenko S.P., Clark E.A., 1993; Sidorenko S.P. et al.,
1995). I?/aiiy iiaa?oiaaeo aioeaai?a aeeth/aei: ?aae?ieiaeoaaiiy
iiaa?oiaaeo AA ee?oei Na125?, a?ioei?eyoe?th iiaa?oi? ee?oei, a oaeiae
iaoaaie?/ia i?/aiiy c aeei?enoaiiyi 32?-i?oioinoaoo Na, 35S-o?aiiiio,
35S-iaoiiiiio, 3I-iaiiice oa 3I-ooeice. A aeayeeo aenia?eiaioao
?ioiii?aoeei?oiaai? a?eee aoee aeaae?eiceeueiaai? ca aeiiiiiaith
oa?iaioo Endo F aeaae?eiceaeace (Boehringer Mannheim, I?ia//eia) oa
aean?ae?ciaai? i?e ia?iaoe? iae?ai?i?aeacith (Sidorenko S.P., Clark
E.A., 1993). Noaoenoe/io ia?iaeo io?eiaieo ?acoeueoao?a aeine?aeaeaiiy
i?iaiaeeee ?c ?ic?aooaaiiyi na?aaeiuei? aaee/eie, iioeaee na?aaeiuei?
aaee/eie, cia/aiiy a?aei?iiinoae i?ae ie?aieie aea??eaie. ?acoeueoaoe
aaaaeaee aeinoia??ieie i?e eiao?oe??io? ae?ia?aeiino? ?<0,05. ?ACOEUeOAOE OA ?O IAAIAI?AIIss Aeni?an?y, a?io?i?/i? aeanoeaino? oa ooieoe?? aioeaai?a, ui aeyaeythoueny IEAO ?II-3, ?II-4, ?II-10 oa ?II-24 C iaoith iiooe?a iiaeo iiaa?oiaaeo aioeaai?a ee?oei aoea noai?aia iaiaeue iiiieeiiaeueieo aioeo?e, ui aeeth/a? IEAO ?II-3, ?II-4, ?II-10 oa ?II-24. Niaoeeoi/iinoue oeeo IEAO aea/aee ia eeioeiieo eiiiyo ?iciiai iioiaeaeaiiy oa iiiiioeeaa?ao ia?eoa??eii? e?iai, ieaaeaeee?a, oeiono oa einoeiaiai iiceo. Aia?eaeiio, ui nae?aoo? IEAO III-3 (IgG1), aoei neiino?oeiaaii o 1983 ?ioei i?ney iioiicaoe?? eeioeiaie eiii? RPMI-1788. IEAO III-3 ?aaaoaaee c A-eiioiaeanoi?aeieie eeioeiieie eiiiyie, A-eeioeiieie eiiiyie Raji, EB-3, Namalwa, Daudi, a oaeiae ICLL-7876, ui iioiaeeoue c AEE. A?eueo?noue O-eeioeiieo eiiie aoee iaaaoeaieie, ? o?eueee ia iiaa?oi? ee?oeiii? e?i?? HPB-ALL ?II-3 aioeaai iiaeia aeyaeoe ca aeiiiiiaith i?ioi/ii? oeeoioeoi?eiao???. Oeae AA ia aoa aeyaeaiee ia iiaa?oii A-eeioeiieo eiiie Ramos, RPMI-8226, Nalm-6, REH. Iaaaoeaieie oaeiae aoee iaeiioi?aeii eeioeiii eiii? (oaae. 1). Oaaeeoey 1 Aca?iiaeiy IEAO na??? ?II c eiiiyie eeioei Eeioeiii eiii? Aioeaai-iiceoeai? ee?oeie (%) iioiaeaeaiiy iacaa ?II-3 ?II-4 ?II-10 ?II-24 A-eiioi- RPMI-1788 51,2+7,2 41,2+3,6 0 50,0+7,5 aeanoi?aeii I?-1 87,4+3,2 89,5+7,4 90,5+5,6 37,5+4,2 T5-1 82,5+6,5 57,7+6,1 98,0+0,5 19,6+1,5 DB 48,3+4,1 17,5+1,2 61,0+4,3 27,0+4,3 CESS 80,1+3,3 24,0+3,1 74,5+6,5 21,0+1,5 6.16 69,0+5,7 38,6+4,4 91,3+2,7 17,5+2,6 PHS 48,8+2,7 35,0+2,7 20,0+3,3 - I?a-A Nalm-6 0 0 - 0 REH 0 0 - 0 AEE HCLL-7876 80,5+6,6 31,1+0,7 14,5+2,5 17,0+4,3 Eiioiia Raji 34,0+2,3 59,0+3,9 86,0+7,4 55,1+6,6 Aa?eiooa Ramos 0 40,0+2,5 0 87,0+5,7 EB-3 15,7+1,9 10,0+0,3 31,0+2,6 0 Namalwa 24,0+0,5 45,0+2,0 82,0+5,7 78,5+4,0 Daudi 32,5+1,5 1,5+0,5 95,0+1,3 80,0+7,1 Mi?eiia RPMI-8226 0 0 50,0+2,5 0 O-eeioeiii CEM 0 10,0+2,1 0 0 eiii? Jurkat 0 61,0+8,3 0 0 CCRF-HSB2 0 10,0+2,0 0 0 MT-4 0 14,5+0,5 0 0 HPB-ALL 28,0+7,5 11,5+1,0 0 0 HUT-78 0 0 0 0 MOLT-4 0 0 0 0 Iaeiioi?aeii E-562 0 0 0 0 eiii? HL-60 0 0 0 0 U937 0 0 0 0 A-431 0 0 0 0 MEWO 0 0 0 0 Aiey 8% iiiiioeeaa?ia ieaaeaeee?a ianee oeae AA, i?e/iio oea aoee A-eeioeie, oae ye aiie aeni?anoaaee CD19 oa CD20 ? ia ianee CD3 i CD2. Ia III-3+ eeioeiao aoa oaeiae aeyaeaiee CD23. ?iaaiue aeni?ani? III-3 AA ia A-eeioeiao ieaaeaeee?a caeaaeaa aiae u?eueiino? eeioei o a?aaei?ioi ia?eieo: aeey iaeeaaoeo eeioeie (iioa?oaca 50/55 oa 45/50) oa?aeoa?ia aeniea u?euei?noue III-3 AA. Oeae aioeaai ia aoa aeni?aniaaiee ia CD19+ /e CD20+ A-eeioeiao ia?eoa?ieii? e?iai, aea aoa aeyaeaiee a iecueeie u?eueiino? ia CD3+ O-eeioeiao e?iai, yei oaeiae ianee CD4 /e CD8. Aiey iieiaeie III-3+ O-eeioei e?iai iaee CD25 AA i aoee CD45RO+, aea CD45RA-. Oei ?acoeueoaoe iieacothoue, ui III-3 AA aeni?aniaaiee ia aeoeaiaaieo O-eeioeiao i ia O-eeioeiao iai’yoi. Aieueoa iieiaeia oeiioeeoia aoea III-3+, i?e/iio III-3+ eeioeie aoee CD45RO+, aea CD45RA-. Aiie oaeiae aeni?anoaaee CD4 ?acii c CD8, aea iaee aiaeiinii iecueeo u?euei?noue CD3. III-3 aioeaai ia aoa aeyaeaiee ia A+CD16+ eeioeiao (NK eeioeie), /e ia ianoeioeueiaaieo /e aeoeaiaaieo (-iioa?oa?iiii iiiioeeoao, aea aeaiae?eoe/i? ee?oeie, aeae?eai? c ia?eoa??eii? e?ia?, ianee oeae aioeaai. III-3 aioeaai ia aoa aeyaeaiee ia eeioeiao aia?iiiaeueii? ia/iiee, a?aioeioeeoao, a?eo?ioeeoao, ii?ei-ea?iioeeoao oa no?iiaeueieo oia?iaeanoao einoeiaiai iiceo. Ia e?iinoaoieo c?icao eiioaoe/ieo aoceia oa ieaaeaeee?a IEAO III-3 oa?aoaaei oieueee ca?iaeeiai oeaio?e A-eeioeiieo oieieoeia oa aiaeioaeiaeueii eeioeie. Iiney noeioeyoei? eiioioeeoia ia?eoa?ieii? e?iai ca aeiiiiiaith iioiaaiia OAA, NinA, PWM ?iaaiue iiceoeaieo eeioei c?inoaa a?ae 4.5% aei 12,6 - 23,5%. Neiaeoth/ei aoaiii noaei aea/aiiy aeni?ani? III-3 AA ia icieueiaaieo iiioeyoeiyo O- i A-eeioei, ui aoee aeoeaiaaii /a?ac niaoeeoi/ii ?aoeaioi?e. IEAO aei CD40, CD20, /e Bgp95, aai aioe-IgM ?acii c aioe-CD40, aoee iaeaieueo aoaeoeaieie a iiaeaeuaiii aeni?ani? III-3 aioeaaio. O oie aea /an naii aioe-IgM IEAO, IL-4 /e ?IA aoee iaio aoaeoeaieie, a noeioeyoe?y (-iioa?oa?iiii ia aeeeeeaea i?aeaeuaiiy ??aiy aeni?an?? ?II-3 aioeaaio. Aeoeaaoeiy O-eeioei /a?ac OE? ca aeiiiiiaith aioe-ND3 IEAO, /e aioe-ND3 a eiiaiiaoei? c aioe-CD28, iiaeaeuoaaea aeni?anith III-3 aioeaaio. O oie aea /an ?IA oa aioe-CD28 naii ia ciiithaaee eiai aeni?anith. Ioaea, ye ia O-, oae i ia A-eiioioeeoao aeni?aniy III-3 AA iiaeaeuo?oueny iiney aeoeaaoei?, aea eiiaoeea oaeiai iiaeaeuaiiy ?icia. Ia A-eeioeiao ?iaaiue III-3 AA iiaeaeuoaaany ia i?ioyci 6 aiaeei iiney aeoeaaoei?, aeinyaath/e iaeneioio /a?ac 24 aiaeeie. O oie aea /an, ia O-eeioeiao aeni?aniy III-3 AA aeinyaaea iaeneioio eeoa ia 3 aeiao iiney aeoeaaoei?. IEAO III-3 iioiii?aoeeiiooaaee c ?aaeiieiaeiaaieo, aai a?ioei?eueiaaieo eeioeiieo eiiie O5-1, 6.16, CESS oa HCLL-7876 aioeaai c i.i. 75-95 eAe. O ia?aaeoeoth/eo oiiaao III-3 aioeaai iia?oaaa ia 5 eAe ieae/a, ui ? naiaeioeoaii oiai, ui oeae aioeaai ? iaeiieaioethaiaith iieaeoeith c aioo?eeaioethaiaeie aeenoeueoiaeieie ca’yceaie. Aeaa?aaeaoeiy III-3 iioiii?aoeeiioaoia ca aeiiiiiaith aeaae?eic?aeace Ando F, iiney yei? i.i. aieeiaiai yae?a III-3 noaiiaeea 42 eAe, aeaco? ia iayai?noue N-ca’ycaieo ieiaioeoe?iaeo aieiaeo eaioetha?a. Iieoaaoeiy c iae?aiiiiaeacith i?eaiaeeea aei cieaeaiiy i.i. III-3 AA i?eaeecii ia 10 eAe, ui naiae/eoue i?i i?enooiinoue oa?iiiaeueieo caeeoeia niaeiai? eeneioe ia oeoe?iaeo eaioethaao. Aeey c’ynoaaiiy iiaeeeainoi anioeiaoei? III-3 AA c eiiacieie aeoeaiinoyie, ie i?iaaee eiiacio ?aaeoeith in vitro ia III-3 iioiii?aoeeiioaoao c eicaoia eeioeiieo eiiie O5-1, CESS oa Jurkat. sse a NP-40, oae i a aeeaioiiiiiaeo eicaoao III-3 aioeaai aoa anioeieiaaiee ye na?ei/o?aiiii, oae i c oe?icei eiiacieie aeoeaiinoyie. Oinoiaiiiieeneioiee aiaeic a?eeiaiai yae?a ?II-3 AA aeyaea oinoi?eethaaiiy ii oe?iceio. Aiioii, ui ?iciiciathoue IEAO III-3, aoa /ooeeaee aei ia?iaee o?eineiii, aea ia/ooeeaei aei iae?aiiiiaeace. Iieoaaoeiy eeioei c ooiieaiioeeiii - iiaiaioi?ii N-aeieiceethaaiiy, ciaiooaaea ?iaaiue aeni?ani? III-3 AA aieueo iiae ia 50%. A ?aieao VI Iiaeia?iaeiiai ?iai/iai aeineiaeaeaiiy aioeaaiia aeeoa?aioeithaaiiy eaeeioeeoia, ui i?ioiaeeei o 1994-1996 ?ieao, iaie aoei iieacaii, ui IEAO ?II-3 oa A12 aeyaeythoue iaeei ? oie aea AA. Aeey oeueiai aoea i?iaaaeaia o?ainoaeoe?y ee?oei e?i?? COS eiiieaiaioa?iith AeIE (pSURslam1), ui eiaeo? SLAM (signalling lymphocyte activation molecule). IEAO A12 oa pSURslam1 eAeIE aoee etha’ycii iaaeai? Dr. G.Aversa (NOA). O?eueee IEAO ?II-3 oa A12 niaoeeo?/ii ?aaaoaaee c o?ainoaeoaioaie. Eiieo?aioia i?eai?/oaaiiy ca’ycoaaiiy aioeoie III-3 c aeei?enoaiiyi IEAO A12 iieacaei, ui oe? aioeo?ea ?ici?ciathoue ??ci? ai?oiie iaeiiai AA. Aeoiaey/e c oeueiai, ia VI Iiaeia?iaei?e eiioa?aioe?? ii aioeaaiai aeeoa?aioeithaaiiy eaeeioeeoia (ssiii?y, 1996), AA, yeee ?ici?ciathoue IEAO ?II-3, io?eiaa i?aeia?iaeio iiiaieeaoo?o CDw150 (Mason D.Y. et al., 1997; Zola H. et al., 1997). Oaeoe, ui III-3 aioeaai (CDw150) anioeieiaaiee c i?ioa?i eiiacieie aeoeaiinoyie, oa eiai aeni?aniy iiaeaeuo?oueny iiney aeoeaaoei?, ? iieacieeaie aeoeaii? ?iei oeueiai AA o i?ioeanao A-eeioeiii? aeoeaaoei?. C iaoith aea/aiiy oaei? iiaeeeainoi, ie iieoaoaaee eeioeie c IEAO III-3 a i?enooiinoi iioaioeieieo einoeioeyoi?ia. Ca’ycoaaiiy CDw150 aioeoieaie ia aeeeeeaei i?ieioa?aoei? oa ia ciiithaaei i?ieioa?aoeaii? aiaeiiaiae? u?eueieo A-eeioei ieaaeaeee?a ia aioe-IgM, aioe-IgM+IL-4, /e aioe-CD20. O oie aea /an IEAO III-3 o eiioeaio?aoeiyo aiae 1,0 aei 5,0 (a/ie nooo?ai iiaeaeuoaaei A-eeioeiio aiaeiiaiaeue ia IL-4, aioe-ND40, IL4+aioe-ND40, /e ?IA. Aeiaeaaaiiy IEAO III-3 o eoeueoo?e O-eeioei a eiiaiiaoeiyo c aioe-ND3, aioe-ND2, aioe-ND4, aioe-ND28 oa ?IA ia aieeaaei ia i?ieioa?aoeaio aiaeiiaiaeue O-eeioei ia?eoa?ieii? e?iai, ca aeeeth/aiiyi aeai?aciai? iiaiaioei? noeioeyoei? ca aeiiiiiaith noaiioeiaeueieo eiioeaio?aoeie aioe-ND3, aai aioe-ND3+aioe-ND28. Ineieueee neaiae /a?ac CDw150 aoa einoeioeyoi?iee c IL-4 oa aioe-ND40, yei ia?aaeathoue neaiaee i?ia?ani?, ie aenoioee a?iioaco, ui oeae neaiae iiaea aooe neaiaeii eiiiaoaioei? aeey A-eeioei. Iiaeaeuaiiy ?iaiy aioo?eeeioeiiiai aieueiiai Na2+ ? iaeia?oith aiaeiiaiaeaeth A-eeioei ia eiiiaoaioii neaiaee /a?ac IgM oa ND19 (Clark E.A., Lane P., 1991). Neaiae /a?ac CDw150 i?eaiaeea aei i?aeaeuaiiy [Na2+]? a 30-50% A-eeioei ieaaeaeee?a, ui ciaoiaeeeenue a noai? niieith. I?ioa, /enei aiaeiiaiaeath/eo eeioei aoei iaioei, i?ae i?e noeioeyoei? /a?ac IgM, ? oei eeioeie ?aaaoaaee ia 40 naeoiae iiciioa. I?e aiaeici ?iciiaeieaiiy A-eeioei ii oacao eeioeiiiai oeeeeo iiney ca’ycoaaiiy CDw150 (caaa?aeaiiy ae?eaeeiiaei i?aiaeaaei) niinoa?iaaeanue oaea ae ea?oeia, ye i i?e noeioeyoei? /a?ac IgM - B-eeioeie aoiaeeee a G1 oaco eeioeiiiai oeeeeo. Oaeei /eiii, neaiae, ui ia?aaea?oueny o A-eeioeie /a?ac CDw150, ? neaiaeii eiiiaoaioei?. IEAO III-3 ia aeeeeeathoue i?ieioa?aoei? A-eeioei, aea iathoue einoeioeyoi?iee aoaeo ?acii c neaiaeaie i?ieioa?aoei?: aioe-CD40, IL-4 oa ?IA. Aia?eaeiio, ui nae?aoo? IEAO III-4 (IgM), aoei neiino?oeiaaii o 1983 ?. i?ney iioiicaoe?? eeioeiaie eiii? RPMI-1788. IEAO III-4 ?aaao? c ee?oeiieie e?i?yie ye O- oae ? A-eeioeiiiai iioiaeaeaiiy (oaae.1). Oeae AA ia aoa aeyaeaiee ia aeayeeo A-eeioeiieo eiiiyo: Daudi, RPMI-8226, Nalm-6, REH; O-eeioeiieo eiiiyo HUT-78, MOLT-4, a oaeiae iaeiioi?aeieo eeioeiieo eiiiyo. Hecueea u?euei?noue oeueiai AA aoea aeyaeaia ia 5-10% O-, A-, NK eeioei oa iiiioeeoia. Aeaieieuei?iaee aiaeic iieacaa, ui IEAO III-4 ?aaaothoue ia?aaaaeii c CD2+CD3+CD45RA-CD45RO+ O-eeioeiaie, ye? i?aaenoaaeaii aeoeaiaaieie e?ioioeeoaie, /e eeioeiaie iai’yoi. Ia aoei ia?aaaaeii? aeni?ani? III-4 AA ia CD4+ aai CD8+ eeioeiao. Aeaieieuei?iaa oa?aoaaiiy eeioei ia?eoa?ieii? e?iai oa ieaaeaeee?a iieacaei i?enooiinoue III-4 aioeaaia ia CD19+CD20+ B-eiioioeeoao. III-4 AA ia aoa aeyaeaiee ia eeioeiao aia?iiiaeueii? ia/iiee, a?aioeioeeoao ia?eoa?ieii? e?iai, ii?eiea?iioeeoao oa no?iiaeueieo oia?iaeanoao einoeiaiai iiceo. Ia e?iinoaoieo c?icao eiioaoe/ieo aoceia oa ieaaeaeee?a IEAO III-4 oa?aoaaei ia?aaaaeii ca?iaeeiai oeaio?e A-eeioeiieo oieieoeia oa aiaeioaeiaeueii eeioeie. Iiney noeioeyoei? eiioioeeoia ia?eoa?ieii? e?iai ca aeiiiiiaith iioiaaiia OAA, NinA, PWM ?iaaiue iiceoeaieo eeioei c?inoaa c 1,5-7,5% aei 11,7-21,7%. ?iaaiue aeni?ani? III-4 AA iiney aeoeaaoei? iiaeaeuo?oueny ye ia O-, oae i ia A-eeioeiao, i?e/iio iiaeaeuo?oueny ia oieueee /enei iiceoeaieo eeioei, aea oaeiae u?euei?noue aioeaaia ia eeioeiieo iaia?aiao. Aeni?aniy III-4 AA ia O-eeioeiao c?inoaea iiney noeioeyoei? Con A, aeoeaaoei? /a?ac CD3 ?acii c CD28, /e ca aeiiiiiaith ?IA. Noeioeyoeiy /a?ac IgM, aai ND20 ia aeaaaea iiaeaeuaiiy ?iaiy III-4 AA, aea aeoeaaoeiy /a?ac CD40 aaea /a?ac 24 aiaeeie i?eaiaeeea aei c?inoaiiy iieo oeoi?anoeaioii? iioaineaiinoi c 2,82 aei 5,27. Eiiaiiaoei? aioe-ND40 IEAO ?acii c aioe-IgM /e IL-4, a oaeiae ?IA aoee iaaioue aieueo aoaeoeaieie. Iiney iaoaaiei/iiai ii/aiiy c aeei?enoaiiyi 3I-iaiice oa 3I-ooeice IEAO III-4 iioiii?aoeeiiooaaee o ?aaeoeoth/eo oiiaao ae?eii?ioa?ae c i.i. 42-46 eAe. C iaoith aea/aiiy ooieoeie AA, yeee ?iciiciathoue IEAO III-4, oei aioeoiea aoee aei?iaiaai? o i?ieioa?aoeaiiio oanoi. U?euei? A-eeioeie ieaaeaeee?a eoeueoeaoaaee o na?aaeiaeui c 10% AON /e c aeiaeaaaiiyi IEAO III-4 o eiiaiiaoei? c ?icieie A-eeioeiieie noeioeyoi?aie: IEAO aei IgM, CD20, CD40 oa IL-4 /e ?IA. Aeiaeaaaiiy IEAO III-4 o eoeueoo?e A-eiioioeeoia ?acii c aioe-IgM, aioe-CD20, aioe-CD40, aioe-CD40+?IA aai IL-4 i?aeoe/ii ia ciiithaaei i?ieioa?aoeaii? aeoeaiino? A-eeioei. O oie aea /an IEAO III-4 aaeai/i i?eai?/oaaee i?ieioa?aoeith A-eeioei, noeioeueiaaieo aioe-CD40+IL-4 aai ?IA. Oneieueee IEAO III-4 i?eai?/oaaee i?ieioa?aoeaio aeoeaiinoue A-eeioei i?e noeioeyoei?, ui aaaea aei aeeoa?aioeithaaiiy, iinoaei ieoaiiy, /e aeeeeeaia oaea i?eai?/oaaiiy cieaeaiiyi i?ieioa?aoeaii? aeoeaiinoi, /e iiaeooue IEAO III-4 aieeaaoe ia aeeoo?caeaoiinoue A-eeioei? Eeioeie eiii? Ramos iiaeooue neoaeeoe ca iiaeaeue aeey aea/aiiy aiiioico (Valentine M.A., Licciardi K.A., 1992). Aeiaeaaaiiy IEAO III-4 a eoeueoo?aeueia na?aaeiaeua aeeeeeaei nia?oue o 10,2+2,7% eeioei, a eiio?ieueii eoeueoo?e iaee 4,76+1,3% ia?oaeo eeioei. IEAO III-4 o eiia?iaoei? c aioeoieaie i?ioe IgM i?eaiaeeee aei c?inoaiiy aiaenioeo ia?oaeo eeioei aei 24,8+4,3%. Oaeei aea aenieei aoa ?iaaiue ia?oaeo eeioei i?e eiiaiiaoei? aioe-IgM+ND40+III-4. I?e ioeiioei i?ioeano aiiioico ca /eneii eeioei c o?aaiaioiaaiith AeIE, aeyaeaii c?inoaiiy aiiioico i?ney ?ieoaaoe?? c IEAO ?II-4 o 2,5 ?ace, a a eiiaiiaoei? c aioe-IgM - aieueo ye o 5 ?acia, iiae a eiio?ieueieo eoeueoo?ao, ui noaiiaeoue iaeaea iieiaeio eeioei a eoeueoo?ao. Eoeueoeaoaaiiy ee?oei ?ioeo e?i?e, iai?eeeaae, Jurkat, Namalwa, Raji, MP-1, CESS, RPMI-1788, a i?enooiino? IEAO ?II-4 (0,5-10 iea/ie) oaeiae aeeeeeaei aiiioic a 30-96% ee?oei. ?acoeueoaoe aiioiii/ieo aeineiaeaeaiue, aea/aiiy aeni?ani? oa ooieoeiiiaeueieo aeanoeainoae aeacothoue, ui IEAO III-4 aeyaeythoue Fas/Apo-1 aioeaai, yeee iaaeith? aiiioic - cai?ia?aiiaaio nia?oue eeioei. IEAO III-4 aoei aeeth/aii aei V Iiaeia?iaeiiai ?iai/iai aeineiaeaeaiiy aioeaaiia aeeoa?aioeithaaiiy eaeeioeeoia. Aiaeic a ?icieo eaai?aoi?iyo iieacaa, ui IEAO III-4 ?acii c o?ueiia iioeie IEAO A?I-1, Fas oa 7N11 ?iciiciathoue A?I-1/Fas aioeaai, yeee io?eiaa iiiaieeaoo?o CD95 (Robertson M., Ritz J., 1994). Aia?eaeiio, ui nae?aoo? IEAO III-10 (IgG3), aoei neiino?oeiaaii o 1984 ?ioei i?ney iioiicaoe?? eeioeiaie eiii? Daudi. IEAO III-10 ?aaaothoue c iiaa?oiaaei AA ia eeioeiao eiiie Daudi, Namalwa, Raji, EB-3 i ia aca?iiae?thoue c eeioeiaie eiii? Ramos (oaae.1). Aeniea u?euei?noue oeueiai AA aoea aeyaeaia ia a?eueoino? A-e?ioiaeanoi?aeieo e?i?e, i?ioa, oieueee 20,0%+3,3 eeioei PHS ianee oeae AA, a eeioeie eiii? RPMI-1788 aoee iaaaoeaieie. III-10 aioeaai aoa aiaenooiie ia iiaa?oiaaeo iaia?aiao eeioei eiiie O-eiioioeeoa?iiai oa iae?ioi?aeiiai iioiaeaeaiiy. Oeae AA aeni?aniaaiee ia 11,5-29,4% iiiiioeeaa?ia ia?eoa?ieii? e?iai, 45-55% ee?oei ieaaeaeee?a oa eiioaoe/ieo aoceia, a oaeiae ia ii?eiea?iioeeoao oa eiioioeeoiiiaeiaieo eeioeiao aia?iiiaeueii? ia/iiee. A?aioeioeeoe, oeiioeeoe, a?eo?ioeeoe oa no?iiaeueii oia?iaeanoe einoeiaiai iiceo aoee iaaaoeaieie. Eiieo?aioia i?eai?/aiiy ca‘ycoaaiiy aioeo?e iieacaei, ui aca?iiae?y IEAO ?II-10 c aioeaaiii ia aeieo?oueny IEAO i?ioe CD19, CD20, CD21, CD24, CD72, CD74, CD78, HLA-DQ, HLA-DP, aea /anoeiai iiaea aooe caaeieiaaia IEAO i?ioe iiiiii?oii? aeaoa?i?iaioe HLA-DR (HB10). Oea aeicaieeei c?iaeoe aeniiaie, ui IEAO ?II-10 ?ici?ciathoue aioeaaiio aeaoa?i?iaioo, ui iaeaaeeoue aei HLA-DR. Ine?eueee IEAO ?II-10 ia ?aaaoaaee c ee?oeiaie Ramos oa RPMI-1788, ia yeeo aeni?aniaai? iiiiii?oi? aeaoa?i?iaioe HLA-DR, IEAO ?II-10 i/aaeaeii ?ici?ciathoue iie?ii?oio aeaoa?i?iaioo HLA-DR. Aaaeeeai, ui ?ieoaaoe?y c IEAO aei CDw78, ui ?ici?ciathoue ai?oiie HLA-DR ? HLA-DQ (Funderud et al., 1997), i?ecaiaeeea aei i?aeaeuaiiy ??aiy aeni?an?? AA, ui eiai ?ici?ciathoue IEAO ?II-10. A e?iinoaoieo c?icao ieaaeaeee?a oa eiioaoe/ieo aoceia IEAT III-10 oa?aoaaei A-eeioeiii oieieoee oa iiiaeeiiei eeioeie o iiaeoieieoey?iie ciii. Oea aioeoiei ?aaaoaaei ye c eeioeiaie iaioi?, oae i c ca?iaeeiaeie oeaio?aie eiioi?aeieo oieieoeia. III-10 aioeaai aoa oaeiae aeyaeaiee o oeeoiieacii ainoiioeeoia oa iae?ioaaia. Ne?aeoth/ei aoaiii anoaiiaeaiiy niaoeeo?/iino? IEAO ?II-10 aoei aea/aiiy aeni?an?? AA, ui aecia/a?oueny IEAO ?II-10, ia ee?oeiao aeanoo?ainoi?iiaaieo eoeueoo?. *a?ac 24 aiaeeie a eoeueoo?ao ee?oei, noeioeueiaaieo LPS, ia aoei a?aei?/aii nooo?aeo ci?i a e?eueeino? ee?oei, ui ?aaaothoue c IEAO ?II-10. Ia ae?oaee aeaiue eoeueoeaoaaiiy ?o /enei ciaioeeinue aaeai? ii??aiyii c ii/aoeiaei ??aiai (19,8+2,4% oa 9,1+1,3% a?aeiia?aeii). A iiaeaeueoiio aoei a?aei?/aii ??cea i?aeaeuaiiy aeni?an?? aioeaaia, ui aeyaey?oueny IEAO ?II-10. Ia 4-oo aeiao noeioeyoe?? /enei ?II-10+ ee?oei c?inoaei aei 23,5+2,1%. Ia?aeaeueii aoea aea/aia aeeiai?ea aeni?an?? AA, ui aecia/a?oueny IEAO ?EI-1 (i?io. A.TH. Aa?eoieeia, ?in?y) ? iai?aaeai? aei iiiiii?oii? aeaoa?i?iaioe HLA-DR. A eoeueoo?ao e?ioioeeo?a aei aeiaeaaaiiy PWM ?II-10+ ee?oeie noaiiaeee 15,1+1,8%,a ?EI-1+ ee?oeie - 14,9+2,7%. I?e aeni?an?? aioeaai?a, ui aecia/athoueny oeeie aioeo?eaie, niinoa??aaee ia 7-e aeaiue eoeueoeaoaaiiy. A?i aeinyaaa 27,3+3,2% aeey AA, ui aeyaey?oueny IEAO ?II-10, oa 26,7+2,7% aeey HLA-DR, aea aeeiai?ea aeni?an?? oeeo aioeaai?a ia 2-6 aeiao aoea ??ciith. *enei ?EI-1+ ee?oei iinooiiai c?inoaei, a ?II-10+ ee?oei - ??cei iaaeaei ia ae?oao aeiao, /anii aeinyaath/e ioey, a ii/eiath/e c 4 aeiae c?inoaei ? ia 7 aeiao aeinyaaei iaeneioia. ConA oa OAA ia aieeaaee ia a?aeiinio e?euee?noue ee?oei, ui ?aaaothoue c IEAO ?II-10. Aeey aiioiii/iiai aiaeico AA, ui ?aaao? c IEAO III-10, iiaa?oiaai aioeaaie eeioei eiiie O5-1 oa Raji aoee ii/aii 125I, ? i?ney nietha?e?caoe?? eeioei IEAO III-10 i?aoeeiiooaaee aeeia? i.i. 33/28 eAe. Iaoaaiei/ia ii/aiiy 35S-iaoiiiiiii oa 35S-oeenoa?iii oaeiae aeyaeei iiae?aio a?io?i?/io no?oeoo?o III-10 AA. Ineieueee ca’ycoaaiiy IEAO III-10 c eeioeiaie aoei o?eueee /anoeiai aeieiaaia IEAO aei iiiiii?oii? aeaoa?iiiaioe HLA-DR, c?iaeaii aeniiaie, ui 33 eAe iieina aiaeiiaiaea? (-eaioethao, a 28 eAe - (-eaioethao HLA-DR, aea IEAO ?II-10 aeyaeythoue iie?ii?oio aeaoa?i?iaioo HLA-DR. Aia?eaeiio, yea nae?aoo? IEAO III-24 (IgG2b), aoei neiino?oeiaaii o 1986 ?ioei i?ney iioiicaoe?? eeioeiaie naeaciiee oai?iai ia aieinaoiee?oeiiee eaeeic. Oea aioeoiei ?aaaoaaei c AA ia iiaa?oii a?eueoino? eeioeiieo eiiie, ui iathoue A-eiioioeeoa?ia iioiaeaeaiiy. I?ioa, ?II-24 aioeaai ia aoa aeyaeaiee ia iiaa?oii i?a-A-eeioeiieo eiiie Nalm-6, REH, a oaeiae i??eiiii? e?i?? ee?oei RPMI-8226. Iaaaoeaieie aoee iaeiioi?aeii ? O-eeioeiii eiii? (oaae. 1). IEAO ?II-24 ?aaaoaaei c 8,0-14,0% iiiiioeeaa?ia ia?eoa?ieii? e?iai oa 28,0-65,0% eeioei eiioaoe/ieo aoceia oa ieaaeaeee?a. Aeaieieuei?iaa oa?aoaaiiy eeioei ia?eoa?ieii? e?iai oa ieaaeaeee?a iieacaei i?enooiinoue III-24 AA i?aeoe/ii ia an?o CD19+CD20+ B-eiioioeeoao, aea aeoaea iecueea u?euei?noue oeueiai AA aoea ciaeaeaia oaeiae ia 2,5-7,5% CD3+ O-eiioioeeoao. A e?iinoaoieo c?icao ieaaeaeee?a IEAO III-24 aeyaeyei eiioioeeoe iaioieii? ciie oa ca?iaeeiaeo oeaio?ia eiioi?aeieo oieieoeia, i?e/iio iaeaieueo ae?aaeaia ?aaeoeiy aiaecia/aeany o iaioieiie ciii. O-eeioeiii ciie caeeoaeenue iaoa?aiaaieie. Iae?ioaae oa aeaio?eoe/ii eeioeie oaeiae aoee iaaaoeaieie. Aioeaai, ui aeyaeythoue IEAO III-24, i?enooiie ia oieueee ia iiaa?oii eiioioeeoia, aea oaeiae i a oeeoiieacii eeioei. I?ioa, a?i ia aoa aeyaeaiee ia eeioeiao aia?iiiaeueii? ia/iiee, a?aioeioeeoao ia?eoa?ieii? e?iai, ii?eiea?iioeeoao oa no?iiaeueieo oia?iaeanoao einoeiaiai iiceo. Eiieo?aioia i?eai?/oaaiiy ca’ycoaaiiy aioeoie aeyaeei, ui IEAO III-24 ?iciiciathoue aioeaai CD37: ca’ycoaaiiy aioeoie III-24 aoei iiaiinoth aeieiaaia aiaeiieie aioe-CD37 IEAO (G28-1), o oie aea /an IEAO aei CD19, CD20, CD21, CD22, CD72, CD76 oa HLA-DR ia i?eai?/oaaee aca(iiaeith IEAO III-24 c aioeaaiii. Aiae?c aeanoeainoae IEAO III-24 a ?aieao V oa VI Iiaeia?iaeieo ?iai/eo aeineiaeaeaiue aioeaaiia aeeoa?aioe?thaaiiy eaeeioeeoia iiaeoaa?aeea, ui IEAO III-24 ?acii c 6 iioeie IEAO ?iciiciathoue ND37 aioeaai (Schlossman S.F. et al., 1995; Kishimoto T. et al., 1997). Ine?eueee CD37 aeyaeaiee ia c?ieeo A-eeioeiao i ?iaaiue oeueiai aioeaaia cieaeaiee ia A-eiioiaeanoi?aeieo eiiiyo, ie iinoaaeee niai ca iaoo aeineiaeeoe, ye ciiith?oueny ?iaaiue aeni?ani? oeueiai AA iiney aeoeaaoei? A-eiioioeeoia. I?e oeo oeiao noeioeyoei?, aea aeiiiiothoue i?ioeane i?ieioa?aoei? (aioe-IgM, aioe-CD40), ciiie ?iaiy aeni?ani? CD37 ia i?ioyci o?ueio aeia aoee ianooo?aeie. Aeoeaaoeiy, ui aaaea aei aeeoa?aioeithaaiiy (aioe-IgM+aioe-CD40, aioe-IgM+IL-4, aioe-CD20 oa ?IA), i?eaiaeeea aei ?iceiai cieaeaiiy /enea iiceoeaieo eeioei oa ?iaiy aeni?ani? CD37 AA. Oea aeaco?, ui A-eiioioeeoe aoaeyoue oeae AA c iiaa?oii o i?ioeani aeeoa?aioeithaaiiy. A ooieoeiiiaeueieo aeineiaeaeaiiyo ie aeei?enoaee o?e iiaeoiaee: i?ieioa?aoeaiee oano, aa?aaaoeiy eeioei oa aieea ia aiino [Ca2+]i. Eoeueoeaoaaiiy A-eiioioeeoia c IEAO III-24 ia aieeaaei ia ?x i?ieioa?aoeaio aeoeaiinoue, aea ?acii c aioe-IgM, aioe-IgM+IL-4, IL-4 /e ?IA aeaaaei einoeioethth/ee aoaeo. Eiiaiiaoei? IEAO III-24 c aioe-CD40 /e aioe-ND20 ia aeaaaee einoeioethth/iai aoaeoo. IEAO III-24, ye i iioi IEAO aei CD37, aeeeeeathoue aa?aaaoeith A-eeioei a eoeueoo?ao in vitro. Oaeee aea aoaeo aoa i?e aeiaeaaaiii IEAO III-24 a eiiaiiaoeiyo c oniia noeioeyoi?aie. Oea ? iiaeeeaoi?ii aiiioeii/ii? aa?aaaoei? A-eiioioeeoia. Ca’ycoaaiiy IEAO III-24 c AA ia iiaa?oii A-eiioioeeoia ia aieeaaei ia ?iaaiue [Ca2+]i. ?acoeueoaoe ooieoeiiiaeueieo aeineiaeaeaiue aeacothoue ia ca’ycie CD37 AA c i?ieioa?aoei?th oa aeic?iaaiiyi A-eeioei ia aioeaai-caeaaeiiio aoaii aeeoa?aioeithaaiiy, ui aeaco? ia iiaeeeaee ca’ycie ND37 c aaaeeeaeie oiciieiai/ieie ooieoeiyie, ui aeeiiothoue c?iei A-eiioioeeoe. Oaeei /eiii, iaie aoee aecia/ai? aioeaaie, ui aeyaeythoueny IEAO na??? ?II, a naia: CDw150 (?II-3), CD95 (?II-4), iie?ii?oia aeaoa?i?iaioa HLA-DR (?II-10) oa CD37 (?II-24). Aeni?an?y aioeaai?a, ui aeyaeythoueny IEAO na??? ?II, i?e eaeeicao oa e?ioiiao Aeni?an?th aioeaai?a CDw150 (?II-3), CD95 (?II-4), iie?ii?oii? aeaoa?i?iaioe HLA-DR (?II-10) oa CD37 (?II-24) aea/aee ia ee?oeiao e?ia?, e?ioaoe/ieo aoce?a oa naeac?iee oai?eo ia aino?ee e?ioiaeanoiee eaeeic (AEE), aino?ee i??eiaeanoiee eaeeic (AIE), o?ii?/iee e?ioieae-eic (OEE), aieinaoiee?oeiiee eaeeic (AEE), i??eiiio oai?iao (IO), iaaiaeaee?inuee? ceiye?ni? e?ioiie (ICE) oa e?ioia?aioeaiaoic (EAI). Ae?aaiic aacoaaany ia aiae?c? ee?i?ei-aaiaoieia?/ieo, ii?oieia?/ieo oa ?ioiieia?/ieo aeaieo. Aeey anoaiiaeaiiy ?ioiieia?/ieo aa??aio?a eaeeic?a oa e?ioii aoee aeei?enoai? IEAO i?ioe CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD20, CD22, CD23, CD25, CD37, aaaeeeo oa eaaeeo eaioetha?a Ig, a oaeiae IEAO ?EI-1, iai?aaeai? i?ioe iiiiii?oii? aeaoa?i?iaioe HLA-DR. I?e aea/aii? aino?iai e?ioiaeanoiiai eaeeico (AEE) a nai?e ?iaio? ie a?oiooaaeenue ia eeaneo?eaoe?? AEE, ?ic?iaeaii? ?a?iiaenueeith a?oiith ii ?ioiieia?/i?e oa?aeoa?enoeoe? eaeeic?a (European Group for the immunological characterisation of leukemias, EGIL) [Aaia I.E. e ae?., 1996], ca?aeii yei? aeine?aeaeai? iaie aeiaaeee aoee a?aeianai? aei ne?aeoth/eo aa??aio?a AEE: O-I aa??aio AEE (7 aeiaaee?a) - oa?aeoa?ecoaaany iayai?noth CD2, CD5 oa/aai CD7, noCD3 aioeaai?a. Ii?iaeueiei aiaeiaii ? i?ioeiioeeoe oa noaei?oeeaeuei? oeiioeeoe. O-II aa??aio (5 aeiaaee?a) - ee?oeie aeni?anothoue ia?ea?e, oa?aeoa?i? aeey O-I aa??aioo oa ND4, CD8 aioeaaie. Ii?iaeueiee aiaeia - ei?oeeaeuei? oeiioeeoe. B-I aa??aio AEE (7 aeiaaee?a) iaa ne?aeoth/ee oaiioei aeanoieo ee?oei: HLA-DR+, CD19+, cyCD22+, CD10-, CD20-, cy(-, sIg-. Ii?iaeueiee aiaeia - i?i-A-ee?oeie. B-II aa??aio AEE (4 aeiaaeee), i?e yeiio aeanoi? ee?oeie iaee oaiioei: HLA-DR+, CD19+, CD10+, CD22+, CD20+, cy(-, sIg-. Ii?iaeueiee aiaeia - i?a-i?a-A-ee?oeie. B-III aa??aio AEE (3 aeiaaeee) oa?aeoa?ecoaaany oaiioeiii: HLA-DR+, CD19+, CD20+, CD22+, cy(+, CD10+, sIg-. Ii?iaeueiee aiaeia - i?a-A-ee?oeie. B-IV aa??aio AEE (1 aeiaaeie) iaa ?ioiioaiioei: HLA-DR+, CD19+, CD20+, CD22+, cy(-, CD10-, sIg+. Ii?iaeueiee aiaeia - c??e? A-ee?oeie. Oaaeeoey 2 Aca?iiaeiy IEAO na??? ?II c iooeeiieie eeioeiaie i?e eaeeicao oa eiioiiao ethaeae Ia’?eo E?euee?noue iiceoeaieo aeiaaeeia, % aeineiaeaeaiiy NDw150 (?II-3) CD95 (?II-4) HLA-DR* (?II-10) CD37 (?II-24) Eeioeie e?iai i?e: B-I AEE 0 33,3 50,0 0 B-II AEE 0 50,0 100 0 B-III AEE - - 100 33,3 A-IV AEE 0 0 0 100 O1-AEE 0 0 0 0 O2-AEE 0 66,7 0 0 OEE 6,7 10,0 62,9 100 AEE 71,4 71,4 100 100 IO 12,5 12,5 25,0 33,3 A-ICE 0 0 33,3 100 I2 AIE 0 0 0 0 I4 AIE 0 0 50,0 0 I5 AIE 0 0 0 0 Eeioeie eiioaoe/ieo aoceia i?e: A-ICE 25,0 66,7 86,7 100 EAI 33,3 55,6 80,0 100 Eeioeie naeaciiee i?e AEE 100 100 100 100 * iie?ii?oia aeaoa?i?iaioa, - aeine?aeaeaiiy ia i?iaiaeeee A aeiaeiiio ?c aea/aieo aeiaaee?a ia aeanoieo ee?oeiao ia aaeaeinue anoaiiaeoe aeni?an?? CDw150, ui na?ae/eoue i?i eiai a?aenooi?noue ia ?aii?o noaae?yo aeeoa?aioe?thaaiiy O- ? A-e?ioioeeo?a. A oiae? aea/aiiy aeni?an?? CD95 ia ee?oeiao ia?eoa??eii? e?ia? oai?eo AEE anoaiiaeaia iayai?noue oeueiai ia?ea?a i?e aeayeeo aa??aioao AEE. Aioeaai CD95 aoa aeni?aniaaiee ia aeanoieo ee?oeiao o 33,3% aeiaaee?a B-I AEE. I?e B-II aa??aio AEE o 50,0% aeiaaee?a ia 20-23% ee?oei aoei oaeiae aeyaeaii oeae AA. Ia iaea?eueo c??eeo ee?oeiao oai?iai c oaiioeiii A-IV AEE CD95 ia aoa aeni?aniaaiee. Oaeei /eiii, na?aae a?oie oai?eo ia AEE, aeanoi? ee?oeie yeeo iathoue A-e?i?eio iai?aaeai?noue aeeoa?aioe?thaaiiy, iaea?eueoa /anoioa aeni?an?? CD95 niinoa??aa?oueny i?e aa??aio? B-II AEE. I?e O-I AEE CD95 aioeaai ia aoa aeyaeaiee ia iiaa?oi? aeanoieo ee?oei, aea o 66,7% aeiaaee?a O-II AEE IEAO ?II-4 ?aaaoaaee c 18,4-56,0% iiiiioeeaa?ieo ee?oei ia?eoa??eii? e?ia?. Ca?aeii c ?acoeueoaoaie ?iaioe, i?iaaaeaii? A.TH.Aa?eoieeiaei ? ni?a. (Aa?uoieeia A.TH. e ae?., 1998a,a), aeyaeaiiy CD95 ca aeiiiiiaith IEAO ?II-4 ia ee?oeiao oai?eo AEE ia? i?iaiinoe/ia cia/aiiy. Aeni?an?y CD95 ia iaia?aiao aeanoieo ee?oei ? i?iaiinoe/ii ni?eyoeeaith iciaeith, ui iia’ycaia ?c ca?eueoaiiyi ye aac?aoeeaeeaii?, oae ? caaaeueii? o?eaaeino? aeeooy. Oaeei /eiii, ?acoeueoaoe aea/aiiy aeni?an?? CD95 ia aeanoieo ee?oeiao oai?eo i?e ??cieo aa??aioao AEE O- oa A-ee?oeiiai iioiaeaeaiiy iieacaee aeioe?euei?noue eiai ?aeaioeo?eaoe??. Aioeaai, ui aeyaey?oueny IEAO ?II-10, ia aoa aeni?aniaaiee ia aeanoieo ee?oeiao oai?eo i?e O-I ? O-II aa??aioao AEE. O anio aea/aieo aeiaaeeao B-I AEE aeanoii eeioeie ?aaaoaaee c IEAO IEI-1, ye? ?iciiciathoue ioiiii?oio aeaoa?iiiaioo HLA-DR, ? eeoa o 50,0% oai?eo ee?oeie aoee ?II-10+. ?acoeueoaoe oeeo aeine?aeaeaiue aeicaieythoue i?eionoeoe, ui ?II-10+ ee?oeie c‘yaeythoueny ia noaae?? ?aii?o iiia?aaeiee?a A-e?ioioeeo?a, a aioeaaii? aeaoa?i?iaioe, ui ?ici?ciathoueny IEAO ?II-10 oa ?EI-1, ia ?aeaioe/i?. Aeoiaey/e c oeueiai, iiaeia aeae?eeoe ne?aeoth/? i?aeaa??aioe A-I AEE: 1) HLA-DR+, ?II-10-, CD19+, CD20-, CD10-, ND37-, CD40-, cyCD22-, cy(-, sIg-. 2) HLA-DR+, ?II-10+ CD19+, CD20-, CD10-, ND37-, CD40-, cyCD22-, cy(-, sIg-. I?e A-II oa B-III aa??aioao AEE aeanoi? ee?oeie ianee aioeaai, ui aeyaey?oueny IEAO ?II-10, a oaeiae ?aaaoaaee c IEAO ?EI-1. I?e A-IV AEE aeni?an?th AA, ui aecia/a?oueny IEAO ?II-10, iai ia aaeaeinue anoaiiaeoe. AA, ui aeyaey?oueny IEAO ?II-24 (CD37), ia aoa aeni?aniaaiee ia aeanoieo ee?oeiao oai?eo a aeiaeiiio ?c aea/aieo aeiaaee?a O-I ? O-II AEE. Iaeiaio aeeoa?aioe?eiaai? aeiaaeee AEE A-ee?oeiiiai iioiaeaeaiiy (A-I oa A-II AEE) aoee oaeiae CD37 iaaaoeaieie. Eeoa ia 18,5% ee?oei iaeiiai c o?ueio oai?eo A-III AEE aoei ca?a?no?iaaii iiceoeaio ?aaeoe?th c IEAO ?II-24, aea 64,0% ee?oei ia??oa??eii? e?ia? oai?iai c A-IV AEE aeni?anoaaee oeae AA. Aeoiaey/e c oeueiai, iiaeia c?iaeoe aeniiaie i?i iiyao CD37 eeoa i?ney HLA-DR, CD19, CD20, CD22, CD10 aioeaai?a oa oeeoiieaciaoe/ieo (-eaioetha?a Ig ia i?ci?e aioeaai-iacaeaaei?e noaae?? aeeoa?aioe?thaaiiy A-eeioioeeo?a. Iaea?eueo aaaaoi/enaeueio a?oio oai?eo aaiiaeanoicaie A-ee?oeiiiai iioiaeaeaiiy neeaee oai?? o?ii?/iei e?ioieaeeicii (A-OEE). E?ioioeeoe ia?eoa??eii? e?ia? oeeo oai?eo iaee ne?aeoth/ee ?ioiieia?/iee oaiioei: HLA-DR+, CD5+, CD19+, CD20+, CD22+, CD23+, CD25-, sIg+. CD23 aecia-/aee eeoa a 7 ?c 30 aea/aieo aeiaaee?a, aea /enei CD23+ ee?oei neeaaeaei 10-43%. E?euee?noue CDw150+ aeiaaee?a aoea iaaaeeeith. Iaie anoaiiaeaii eeoa 2 aeiaaeee, eiee iiaeia aoei ca?a?no?oaaoe iiceoeaio ?aaeoe?th ia 10-17% ee?oei. Ca?aeii ii?oieia?/ieo aeine?aeaeaiue a?eueo?noue ee?oei oeeo oai?eo iaee iciaee ieaciaoecaoe??, iiaa?oiaa? ? oeeoiieaciaoe/i? Ig. Aeni?an?y CD95 niinoa??aaeanue eeoa a 3 aeiaaeeao OEE ia 10-44,4% ee?oei. Ia?aeaeueia aea/aiiy iiaa?oiaaeo aioeaai?a ee?oei oai?eo OEE oa AA, ui aecia/a?oueny IEAO ?II-10, aeaei ciiao aeae?eeoe aea? a?oie oai?eo A-OEE. A ia?o?e a?oi? oai?eo OEE (18 aeiaaee?a) 37-98% ee?oei ?aaaoaaee c IEAO ?II-10, oiae? ye ia ee?oeiao oai?eo ae?oai? a?oie ia aoee aeyaeai? ?II-10+ ee?oeie. Aea/aiiy ?ioiieia?/ii? oa?aeoa?enoeee ee?oei oai?eo OEE a iaio a?oiao ia anoaiiaeei ??cieoe? a aeni?an?? HLA-DR, CD19, CD20, CD23 oa CD25. I?ioa, na?aae oai?eo ae?oai? a?oie (9 oai?eo) o?eueee iaeei aeiaaeie aoa CD22+. Iiaeeeai, ee?oeie oai?eo oe??? a?oie ciaoiaeeeenue ia i?ci?e aioeaai-caeaaei?e noaae?? aeeoa?aioe?thaaiiy, aeey yei? ia oa?aeoa?ia aeni?an?y CD22 aioeaaio. Aeni?an?y CD37 aoea aeia?a ae?aaeaia ia iiaa?oiaa?e iaia?ai? 72-98% ee?oei an?o aeine?aeaeaieo oai?eo OEE. ?ioiieia?/ia aeine?aeaeaiiy iiaa?oiaaeo ia?ea??a ee?oei e?ia? ? naeac?iee 8 oai?eo aieinaoiee?oeiiee eaeeic (AEE) iieacaei, ui a?eueo?noue ee?oei aeni?anoaaee sIg, ILA-DR, CD19, CD22 aioeaaie, a 11-42% ee?oei i?noeee ia?ea? aeoeaiaaieo e?ioioeeo?a CD25. Ia aieinaoeo ee?oeiao ia aoee aeyaeai? CD5, CD10 oa CD23. O 5 ?c 7 aeiaaee?a AEE 10-48% aieinaoeo ee?oei a ia?eoa??ei?e e?ia? aeni?anoaaee CDw150. Ne?ae caoaaaeeoe, ui o oeeo aea aeiaaeeao ia 10-59% ee?oei ia?eoa??eii? e?ia? aoei aeyaeaii CD95. Aieinao? ee?oeie a naeac?ieao 2 oai?eo oaeiae aeni?anoaaee oe? AA. U?euei?noue oeeo ia?ea??a ia ee?oeiao oai?eo aoea aenieith. E??i oiai, oe? ee?oeie aeni?anothoue iie?ii?oio aeaoa?i?iaioo HLA-DR, ui aecia/a?oueny IEAO ?II-10, a ND37, ui aeyaey?oueny IEAO ?II-24, aoa aa?ii ae?aaeaiee ye ia iiaa?oiaa?e iaia?ai? aieinaoeo ee?oei, oae ? a oeeoiieaci?. Ia i?ci?o noaae?yo aeeoa?aioe?thaaiiy A-e?ioioeeo?a CD95 ? CDw150 ia aeyaeythoueny. Oea aoei i?aeoaa?aeaeaii a oiae? aea/aiiy ee?oei oai?eo i??eiiiith oai?iaith (8 aeiaaee?a). Ee?oeie ia?eoa??eii? e?ia? oai?eo iaee ne?aeoth/ee oaiioei - cyIg+, CD19+, HLA-DR+, CD20-, CD22-, CD23-. Eeoa iaaaeeea iiioeyoe?y oaeeo ee?oei o iaeiiai oai?iai aoea CD95+CDw150+. Ana oea na?ae/eoue i?i ao?aoo CD95 ? CDw150 ia oa?i?iaeueieo noaae?yo aeeoa?aioe?thaaiiy A-e?ioioeeo?a. Na?aae aeine?aeaeaieo aeiaaee?a i??eiiii? oai?iae, aeni?an?y CD37 aoea anoaiiaeaia eeoa a iaeiiio aeiaaeeo, a IEAO ?II-10 ?aaaoaaee c A-ee?oeiaie a ia??oa??ei?e e?ia? o?eueee o aeaio oai?eo. Aeni?an?y aioeaai?a, ui aeyaeythoueny IEAO na??? ?II, aoea oaeiae aea/aia ia ee?oeiao e?ioaoe/ieo aoce?a oai?eo ia iaaiaeaee?inuee? ceiye?ni? e?ioiie. I?e iinoaiiaoe? a?noieia?/iiai ae?aaiico ie aeiaea?aeoaaeenue Ia?aaeyiooi? ?a?iiaenueei-aia?eeainueei? eeaneo?eaoe?? e?ioi?aeieo iiaiooai?aiue (REAL) (Harris et al., 1994; I?iaaoiaa e niaao., 1998). Aei oeeo A-ICE iaeaaeaee: 1) A-OEE/i?ie?ioioeeoa?iee eaeeic/e?ioiia c iaeeo e?ioioeeo?a, oaiioei: HLA-DR+, sIg+ iecueea aeni?an?y, cyIg-, CD19+, CD20+, CD22+, CD37+, CD5-, CD10- (2 aeiaaeee). 2) E?ioiia ?c ee?oei ?c oeaio??a oie?eoe?a, oie?eoey?ia, oaiioei: HLA-DR+, sIgM+, cyIg-, CD19+, CD20+, CD22+, CD5-, CD10+/- (4 aeiaaeee). 3) Aeeoocia A-e?oiiiee?oeiia e?ioiia, oaiioei: HLA-DR+, sIg+/-, cyIg+/-, CD19+, CD20+, CD22+, CD5+/-, CD10+/- (3 aeiaaeee). 4) E?ioiia ?c ee?oei iaio?eii? ciie, oaiioei: HLA-DR+, sIgM/D+, cyIg-, CD19+, CD20+, CD22+, CD5+, CD10+/- (3 aeiaaeee). 5) Iioiioeeoiia/e?ioiieaciaoeeoa?ia e?ioiia, oaiioei: HLA-DR+, sIg+, cyIg+, CD19+, CD20+, CD22+, CD5-, CD10- (3 aeiaaeee). I?e eaeeaiicaoei? ICE iaoieia?/i? ee?oeie a ia?eoa??ei?e e?ia? 4-o oai?eo iaee oa?aeoa?i? ?icuaieai? yae?a ? iaee ne?aeoth/ee oaiioei: HLA-DR+, Ig+, cyIg+, CD19+, CD20+, CD22+, CD5-, CD10-. T?eueee 2 aeiaaeee eaeeai?caoe?? ICE oa?aeoa?ecoaaeenue iayai?noth iiaa?oiaaiai oaiioeio HLA-DR+, Ig+, cyIg+, CD19+, CD20+, CD22+, CD5+, CD10-. Na?aae iaaiaeaeeiinueeeo ceiyeinieo eiioii A-eeioeiiiai iioiaeaeaiiy oieueee 3 aeiaaeee aoee III-3 iiceoeaieie. A oeeo aeiaaeeao aoa iinoaaeaiee a?noieia?/iee ae?aaiic - aeeoocia A-e?oiiiee?oeiia e?ioiia (REAL eeaneo?eaoe?y) (neiii?ie: oeaio?iaeanoia, A-?ioiiaeanoia - E?euenueea eeaneo?eaoe?y). A oeeo aeiaaeeao oaiioei iooeeiieo eeioei aiaeiiaiaeaa noaaei? aeeoa?aioe?thaaiiy A-eiioioeeoia, ui ciaoiaeyoueny ia aioeaai-caeaaeiiio aoai? aeic??aaiiy o ca?iaeeiaeo oeaio?ao e?ioi?aeieo oie?eoe?a, a naia, oeaio?iaeanoai oa ?ioiiaeanoai. Iaoieia?/i? ee?oeie o oeeo aeiaaeeao ianee sIg a iecuee?e u?eueiino? ?, e??i iaeiiai aeiaaeea, ia aeni?anoaaee oeeoiieaciaoe/ieo ?ioiiaeiaoe?i?a, aoee HLA-DR+, CD19+, CD20+, CD22+, CD37+, CD5-, a o 1 aeiaaeeo oaeiae aeni?anoaaee CD10 oa CD21. O 60% oai?eo ICE a eiioaoe/ieo aoceao aoee aeyaeaii CD95+ eeioeie, aea ?o aiaenioie ia ia?aaeuoaaa 5,0-22,0%. I?enooi?noue oeueiai AA ia ei?aethaaea c a?noieia?/iei aa??aioii ICE. I?e eaeeaiicaoei? ICE o ia?eoa?ieiie e?iai ie ia ciaeoee CDw150 oa CD95 iiceoeaieo eeioei. Aeniea u?euei?noue CD95 aoea aeyaeaia ia aiioaeii?aeieo eeioeiao i?e eiioiii Eaiia?oa. ?acoeueoaoe aea/aiiy aeni?an?? AA, ui aecia/a?oueny IEAO ?II-10, ia e?iinoaoieo c?icao oa noniaici? ee?oei eiioaoe/ieo aoceia iieacaee, ui aaniethoia aieueoinoue aeiaaeeia A-ICE aoea iiceoeaia. O 3-o aeiaaeeao ?ioiioeeoiie/e?ioiieaciaoeeoa?ii? e?ioiie AA, ui ?ici?cia?oueny IEAO ?II-10, ia aoa aeyaeaiee. ?ioiieia?/iee oaiioei iooeeiieo ee?oei o oeeo aeiaaeeao aoa ne?aeoth/ee: HLA-DR, sIg+, cyIg+, CD19+, CD20+, CD22+, CD37+, CD5-, CD10-. A?iioaoe/iee ii?iaeueiee aiaeia oeeo ee?oei - ia?eoa??eiee A-e?ioioeeo, aeoeaiaaiee aeey ia?aoai?aiiy o ieaciaoe/io ee?oeio. T?eueee 2 aeiaaeee eaeeai?caoe?? ICE oa?aeoa?ecoaaeenue iayai?noth iiaa?oiaaiai ai?oiio, ui ?ici?cia?oueny IEAO ?II-10. Oa?aeoa?iei aeey Ig+, HLA-DR+, CD19+, CD20+, CD22+, CD37+ aeiaaee?a aoea i?enooi?noue iiaa?oiaaeo CD5, i?e a?aenooiino? CD23, ui aeaco? ia iioiaeaeaiiy oeeo ee?oei c ee?oei iaio?eii? ciie e?ioaoe/ieo aoce?a. O 4-o aeiaaeeao eaeeai?caoe?? ICE iaoieia?/i? ee?oeie aoee HLA-DR+, aea ia ?aaaoaaee c IEAO III-10, oi/a ia oeeo ee?oeiao aoea aeyaeaia aeni?an?y iiiiii?oii? aeaoa?i?iaioe HLA-DR. O an?o aeiaaeeao A-ICE IEAO ?II-24 aeyaeyei CD37 ia iiaa?oi? iaoieia?/ieo ee?oei ye a ia?eoa??ei?e e?ia?, oae ? a o?aaeaieo e?ioaoe/ieo aoceao. I?e e?ioia?aioeaiaoic? (EAI) IEAO III-3 oa?aoaaee aa?ithth/o i?iii?oeith eeioei aaeeeiai ?icii?o o 30% aeiaaee?a (i?e aeine?aeaeaii? e??inoaoieo c??c?a), oa 60% aeiaaee?a (i?e aeine?aeaeaii? ee?oeiieo noniaic?e). Aei ?II-3 iiceoeaieo ee?oei iaeaaeaee A- ? O-?ioiiaeanoe, a oaeiae ee?oeie Aiaeaee?ia. O a?eueoino? aeiaaee?a EAI ani?an?y CD95 aoea aeyaeaia ia 10,8-49,8% ee?oei. Oeae aioeaai aoa aeni?aniaaiee ye ia aaaaoiyaea?ieo ee?oeiao Aa?acianueeiai-Ooa?iaa?aa oa ee?oeiao Aiaeaee?ia, oae ? ia e?ioioeeoao. ?acoeueoaoe aea/aiiy aeni?an?? AA, ui aeyaey?oueny IEAO ?II-10, ia e??inoaoieo c??cao oa ee?oeiieo noniaic?yo e?ioaoe/ieo aoce?a oai?eo EAI iieacaee, ui oeae AA i?enooiie ia cia/iie /anoeii eiioioeeoia (30-92%). A o?aaeaieo eiioaoe/ieo aoceao i?e EAI aiae 38,5 aei 67,5% eiioioeeoia aeaaaei iiceoeaio ?aaeoeith c IEAO III-24 (CD37), aea eeioeie Aiaeaeeiia oa Aa?acianueeiai-Ooa?iaa?aa aoee iaaaoeaieie. I?e aea/ai? aeni?an?? aioeaai?a, ui aecia/athoueny IEAO na??? ?II, aoee aeei?enoai? oaeiae ee?oeie ia?eoa??eii? e?ia? oai?eo c iae?ioi?aeiei aa??aioii aino?iai eaeeico - aino?ei i??eiaeanoiei eaeeicii (AIE). Ani aeiaaeee I2 (CD13+, CD33+, CD34+, CD15+, CD14-, HLA-DR+), I4 (CD13+, CD33+, CD34+, CD15+, CD14+, HLA-DR+), I5 (CD13+, CD33+, CD34+, CD15+, CD14+, HLA-DR+) aa??aio?a aino?eo iiaei?aeieo eaeeic?a aoee CDw150, CD95 oa CD37 iaaaoeaieie. IEAO III-10 ia ?aaaoaaee c eaeeicieie eeioeiaie i?e I2 AIE oa I5 AIE, aea a 50% aeiaaeeia I4 AIE aiie oa?aoaaee iiaa?oiaai iaia?aie ii?eiiiiiaeanoia. Oaeei /eiii, aea/aiiy aeni?ani? NDw150 i?e ?icieo oeeoieiai/ieo aa?iaioao eaeeicia oa eiioii ethaeeie aeacothoue, ui oeae aioeaai i?enooiie ia eeioeiiie iiaa?oii o anio aeiaaeeao, aea iaoieiai/ii eeioeie aiaeiiaiaeathoue noaaei? aeoeaiaaieo A-eiioioeeoia, cie?aia i?e AEE, EAI oa aeeoocieo A-e?oiiiee?oeiieo (iioiiaeanoieo) e?ioiiao. Oea ?iaeoue III-3 aioeaai aaaeeeaei ia?ea?ii aeey aeeoa?aioeiaeueii? aeiaaiinoeee oa eeaneoieaoei? A-eeioeiieo aa?iaioia eaeeicia oa eiioii ethaeeie. I?aaenoaaeaii iaie ?acoeueoaoe aea/aiiy aeni?ani? CD95 i?e iooeeiieo caoai?thaaiiyo e?iaioai?ii? oeaieie aeacothoue, ui CD95 aeoaea neaai aeni?aniaaiee ia iaoieiai/ieo eeioeiao i?e eaeeicao oa eiioiiao i aeyaeaiee ia eiioioeeoao c oaiioeiii aeoeaiaaieo eeioei. Oiio ?aaoeyoeiy aeni?ani? CD95 ia iooeeiieo eeioeiao oa iiaeoeoeiy aiiioico a oeeo eeioeiao ? iioeiinoe/iith ia?niaeoeaith iioiioa?aii? iooeei (Green D.R. and Martin S.J., 1995). Iao? aeine?aeaeaiiy iieacaee, ui iieiii?oia aeaoa?iiiaioa, yeo aeyaeythoue IEAO III-10, ia? aeiaaiinoe/io oeiiiinoue: 1) aeey aeeoa?aioeieii? aeiaaiinoeee oa eeaneoieaoei? iiaeaa?iaioia B-I AEE; 2) aeyaeaiiy aenieiaeeoa?aioeieiaaieo aeiaaeeia A-OEE; 3) ooi/iaii? aeeoa?aioeiaeueii? ae?aaiinoeee oa eeaneoieaoei? aenieiaeeoa?aioeieiaaieo A-ICE. O ca’yceo c oei, ui CD37 aeni?aniaaiee aeeeth/ii ia c?ieeo A-eeioeiao, IEAO ?II-24 aei oeueiai AA ?aeiiaiaeiaai? aeey aeei?enoaiiy o aeeoa?aioeiaeueiie ae?aaiinoeoei oa eeaneoieaoei? A-ee?oeiieo oi?i eaeeic?a oa e?ioii. CD37, ye ? CD20, a?aeiineoueny aei n?iaenoaa iieaeoe, ui ia?aoeiathoue ee?oeiio iaia?aio 4 ?ace, ? aca?iiae?y c IEAO ia aeeeeea? ?o iiaeoeyoe?th. A?aoiaoth/e oea, IEAO aei CD37 ciaeoee oe?iea aeei?enoaiiy a ?ioiioa?ai?? ICE (Bonardi M.A. et al., 1993; Gidlof C. et al., 1995). E??i oiai, IEAO aei CD37 iathoue ia?aaaao ia?aae aioe-CD20 IEAO, oiio ui CD37, ia a?aei?io a?ae CD20, ia aeni?aniaai? ia A-ee?oeiao iiia?aaeieeao o e?noeiaiio iiceo. Oea aeicaiey? aeinyaaoe a?eueoi? naeaeoeaiino? i?e ?ioiioa?ai?? ICE, oa aeei?enoiaoaaoe aioe-CD37 IEAO aeey i/euaiiy e?noeiaiai iiceo a?ae iooeeiieo ee?oei i?e ICE (Press O.W. et al., 1993; Brown R.S. et al., 1997). Oaeei /eiii, iaie ?ic?iaeaia iaiaeue iiiieeiiaeueieo aioeoie aei aioeaaiia aeeoa?aioeithaaiiy eiioioeeoia, ui aeeth/a? IEAO III-3 (aioe-CDw150), III-4 (aioe-CD95), III-10 (aioe-HLA-DR) oa III-24 (aioe-CD37), ia? aaeeeo oeiiiinoue aeey aea/aiiy i?ioeania aeeoa?aioeithaaiiy eiioioeeoia a ii?ii oa i?e iaoieiai? ? iiaea aooe ?aeiiaiaeiaaia aeey aeei?enoaiiy o ?ioiioaiioeioaaii?, ae?aaiinoeoe?, eeaneoieaoei? oa ?ioiioa?ai?? iooeeiieo caoai?thaaiue e?iaioai?ii? oeaieie. ?aaoeyoe?y aeeoa?aioe?thaaiiy A-ee?oei /a?ac iiaa?oiaa? ?aoeaioi?e Aeeoa?aioe?thaaiiy A-ee?oei eiio?ieth?oueny ye aaiaoe/iith i?ia?aiith, oae ? neaiaeaie, ye? iaaeoiaeyoue o A-ee?oeie c iicaee?oeiiiai na?aaeiaeua. Cae/aeii, oe? neaiaee iinooiathoue /a?ac iiaa?oiaa? ?aoeaioi?e, ye? ca’ycothoueny ?ic/eiieie oa ?iia?e?ciaaieie e?aaiaeaie. Eeth/ia? iiceoe?? o ?aaoeyoe?? aeeoa?aioe?thaaiiy A-ee?oei iaeaaeaoue A-ee?oeiiiio ?aoeaioi?o (AE?) oa CD95/Fas. Iaie aoee aecia/ai? eiiiiiaioe neaiaeueieo oeyo?a, ye? aeoeaothoueny a A-ee?oeiao i?ney ia?aaea/? neaiaeo eiiiaoaioe?? /a?ac AE? o A-ee?oeiieo e?i?yo Daudi oa Ramos, ui iioiaeyoue c e?ioiie Aa?e?ooa. Oeaio?aeueiei eaioethaii oeeo eaneaae?a ? i?ioa?i oe?icei e?iaca Syk. Iaie aoea ?cieueiaaia eiiieaiaioa?ia AeIE, ui eiaeo? Syk ethaeeie. Oey eAeIE, aeiaaeeiith o 635 ai?iieeneio, eiaeo? a?eie ?ici??ii 72 eAe c aeaiia N-oa?i?iaeueieie SH2 aeiiaiaie oa e?iaciei aeiiaiii. Ca aeiiiiiaith Northern oa Western aeio aiae?co aoei iieacaii, ui Syk aeni?aniaaiee a A-ee?oeiieo e?i?yo ia ??cieo noaae?yo aeeoa?aioe?thaaiiy, o ?yae? O-ee?oeiieo e?i?e, iai?eeeaae MOLT-4 oa Jurkat, a oaeiae a ee?oeiieo e?i?yo i??ei?aeiiai iioiaeaeaiiy (HL60 oa U937). Aeei?enoiaoth/e iine?aeiaio ?ai?aoeei?oaoe?th i?ney e?iacii? ?aaeoe?? in vitro oa WB, iaie aoee ?aeaioeo?eiaai? ne?aeoth/? iieaeoee, ui anioe?eiaai? c Syk o A-ee?oeiao ? ca’ycothoue AE? c ??cieie neaiaeueieie eaneaaeaie: 53/56 eAe Lyn i?ioa?i oe?icei e?iaca, ui iaeaaeeoue aei ?iaeeie Src; PLC(1, ui ? noano?aoii aeey Syk, oa aca?iiae?? c oinoi?eeueiaaiei oe?iceiii, yeee ciaoiaeeoueny i?ae e?iaciei oa SH2 aeiiaiaie a iieaeoe? Syk; 120 eAe oinoii?ioa?i (?120) aoa ?aeaioeo?eiaaiee ye iiaa na?ei/o?aii?i e?iaca ?EN(. Oaeiae aoei iieacaii, ui aeoeaaoe?y A-ee?oei /a?ac AE? aeceaa? ?aeieae?caoe?th Syk, PLC(1, ?EN( oa Shc c oeeoicieth aei iaia?ai. Neaiae eiiiaoaioe?? /a?ac CDw150 aeei?enoiao? a?aei?ii? a?ae AE? iaoai?cie. Iaie aoee ?aeaioeo?eiaai? iieaeoee, ye? ca’ycothoue CDw150 c neaiaeueieie eaneaaeaie, ui ?aaoeththoue i?ioeane aeeoa?aioe?thaaiiy. Aeey oeueiai aoa aeei?enoaiee o?ia?iee a?eie i?ae oeeoiieaciaoe/iith /anoeiith CDw150 oa aethoao?ii-S-o?ainoa?acith (GST) - GST-CDw150ct oa eiai oe?icei-oinoi?eeueiaaia oi?ia (GST-CDw150ct-PY). Iieacaii, ui CDw150 anioe?eiaaiee c i?ioa?i oe?icei e?iacith Fgr, i?ioa?i oe?icei oinoaoacith CD45, a oaeiae c oinoi?iic?oie oinoaoacith SHIP. Oe? o?e iieaeoee ca’ycai? c ?aaoeyoe??th aeeoa?aioe?aoe?? ee?oei oa aiiioico (Katagiri K. et al., 1996; Klaus S.J. et al., 1996; Ono M. et al., 1997). E??i oiai, CDw150 aeyaeaiee iaie ia A-ee?oeiao, ui aeni?anothoue CD95, iai?eeeaae, ia A-e?ioiaeanoi?aeieo e?i?yo ee?oei. Aeoiaey/e c oeueiai, ie aenoioee a?iioaco, ui e?aaoe?y CDw150 ia iiaa?oi? ee?oei iiaeoeth? CD95-iiina?aaeeiaaiee aiiioic. Iaie aoei anoaiiaeaii, ui ia i?ci?o aoaiao aeic??aaiiy A-ee?oei neaiae /a?ac CDw150 ? neia?a?/iei c CD95-iiina?aaeeiaaiei aiiioicii. A A-ee?oeiieo e?i?yo, oaeeo ye Raji, RPMI-1788 oa MP-1, IEAO ?II-3 aeceaa? neia?a?/iee aoaeo c CD95. Iai?eeeaae, i?a?ieoaaoe?y ee?oei I?-1 c IEAO ?II-3 ia?aae aeiaeaaaiiyi IEAO ?II-4 i?eaiaeeea aei i?aeaeuaiiy ??aiy aiiioicieo ee?oei c 42,0+3,0 aei 67,8+2,4%. A oeeo e?i?yo ee?oei aioe-CD40 IEAO ?yoothoue a?ae CD95-iiina?aaeeiaaiiai aiiioico, a neaiae /a?ac CDw150 iiai?noth a?aeiiaeth? CD95-iiina?aaeeiaaiee aiiioic, aenooiath/e ye aioaaii?no CD40. E?iaoe/i? aenia?eiaioe iieacaee, ui oaeee neia?a?ci aaea iii?oiee /a?ac 3 aiaeeie i?ney e?aaoe?? CD95, aeinyaath/e iaeneioio /a?ac 24 aiaeeie. Oeae iiaeoethth/ee aoaeo IEAO ?II-3 iiaea aooe aeei?enoaiei aeey ?aaoethaaiiy aeeoa?aioe?thaaiiy A-ee?oei, a oaeiae aeey ?ioiioa?ai?? iooeei, ui aeni?anothoue ND95 oa CDw150. Iaie oaeiae aoei ciaeaeaii, ui neaiae /a?ac CD40 iiaeoeth? CD95-iiina?aaeeiaaiee aiiioic ia o?eueee a ii?iaeueieo A-ee?oeiao, aea oaeiae ? a iaoieia?/ieo ee?oeiao i?e OEE (10 oai?eo). Ee?oeie oai?eo OEE iaee iecueeee ??aaiue aeni?an?? CD95. Iaie a?aei?/aia iiceoeaia ?aaeoe?y o 3 aeiaaeeao ia 4-8% ee?oei oai?eo OEE. I?ney 48 aiaeei noeioeyoe?? aioe-CD40 IEAO, ??aaiue aeni?an?? CD95 a a?eueoino? aeiaaee?a i?aeaeuoaaany aei 60-78%. Ia iaoieia?/ieo ee?oeiao aeaio oai?eo ia aaeaeinue aeyaeoe ci?ie a aeni?an?? CD95. ?acoeueoaoe aea/aiiy CD95-iiina?aaeeiaaiiai aiiioico A-e?ioioeeo?a oai?eo OEE, iiia?aaeiuei noeioeueiaaieo aioe-CD40 IEAO, aeyaeee aaoa?iaai?noue na?aae aeine?aeaeaieo aeiaaee?a. Iaie aoee aeae?eai? aeaa aa??aioe OEE. I?e ia?oiio aa??aio? (7 oai?eo) ceiye?ni? ee?oeie i?ney iiia?aaeiuei? ?ieoaaoe?? c aioe-CD40 IEAO noaaaee /ooeeaeie aei CD95-iiina?aaeeiaaiiai aiiioico ? ??aaiue aiiioicieo ee?oei aeinyaaa 33,0-66,0%. I?e ae?oaiio aa??aio? OEE (3 oai?eo) a ceiye?nieo ee?oeiao neaiae /a?ac CD40 i?eai?/oaaa CD95-iaae?eiaaiee aiiioic, iacaaaeath/e ia ?iaeoeoe?th aenieiai ??aiy CD95+ ee?oei. Iaoieia?/i? ee?oeie i?e oeeo aa??aioao a?ae??ciyeenue ca nooiaiai c??eino?: ee?oeie i?e ae?oaiio aa??aio? aoee a?eueo aeeoa?aioe?eiaaieie. Oaeei /eiii, iaie aoee aeae?eai? 2 aa??aioe OEE, i?e yeeo neaiaee /a?ac CD40 oa CD95 ? neia?a?/ieie, aai aioaaii?noe/ieie. Oea ia? aaeeea cia/aiiy aeey ?icoi?iiy iaoiaaiaco caoai?thaaiiy, a oaeiae aeey ?ic?iaee no?aoaa?? ?ioiioa?ai?? c aeei?enoaiiyi IEAO i?ioe aioeaai?a, neaiaee /a?ac ye? ?aaoeththoue aeeoa?aioe?thaaiiy ee?oei. BENIIAEE Coai?aia ia?oa aio/eciyia iaiaeue iiiieeiiaeueieo aioeoie i?ioe iiaa?oiaaeo aioeaai?a aeeoa?aioeithaaiiy eiioioeeoia ethaeeie aeey aeei?enoaiiy a iieiaaiaoieiai? aeey ?ioiioaiioeioaaiiy, aeeoa?aioeiaeueii? ae?aaiinoeee, eeaneoieaoei? oa ?ioiioa?ai?? eiioi?aeieo oi?i eaeeicia oa eiioii ethaeeie. Aeyaeaii iiaee aeoeaaoeieiee aioeaai CDw150 (?II-3), ui aeni?aniaaiee ia O-, A-, aeaiae?eoe/ieo oa aiaeioaeiaeueieo eeioeiao. ??aaiue aeni?ani? CDw150 iiaeaeuo?oueny iiney aeoeaaoei? /a?ac O- ? A-ee?oeii? aioeaaii? ?aoeaioi?e, CD20, CD40, Bgp95, a oaeiae ca aeiiiiiaith IL-4. Iieacaii, ui CDw150 ? niaeiciaaiei oinoiaeieii?ioa?aeii i.i. 75-95 eAe c aieeiaei yae?ii 42 eAe. Ciaeaeaii, ui CDw150 anioeieiaaiee c ne?ei/o?aiiii i oe?icei eiiacieie aeoeaiinoyie, i?ioa?i oe?icei oinoaoacith CD45, i?ioa?i oe?icei e?iacith Fgr oa oinoi?iic?oie oinoaoacith SHIP. Neaiae, ui ia?aaea?oueny o A-eeioeie /a?ac CDw150, ? neaiaeii eiiiaoaioei?. Aeoeaaoe?y /a?ac CDw150 iiaeoeo? iiaeaeuaiiy ?iaiy [Ca2+]i oa aoiaeaeaiiy A-eeioei o G1 oaco eeioeiiiai oeeeeo. CDw150 aeni?aniaaiee i?e oeo A-eeioeiieo aa?iaioao eaeeicia oa eiioii, aea aeie aeeoa?aioe?thaaiiy aeiee ia aoaiao aeoeaaoe?? A-eeioei: i?e aieinaoiee?oeiiiio eaeeic?, e?ioia?aioeaiaoic? oa aeeoocieo A-e?oiiiee?oeiieo iaaiaeaee?inueeeo ceiye?nieo e?ioiiao. Aia?oa io?eiaii iiiieeiiaeuei? aioeo?ea III-4, ui ?iciiciathoue CD95 aioeaai i.i. 42-46 eAe, yeee iaaeith? aiiioic. Anoaiiaeaia aeni?an?y CD95 i?e ??cieo oi?iao aaiiaeanoic?a. Aeyaeaia iiaeoeoeiy aeni?ani? CD95 ia A-eeioeiao iiney aeoeaaoei? /a?ac CD40, CD40+IL-4, aai ND40+IgM. Aia?oa iieacaia aioaaiiinoe/ia aeiy aioe-ND95 IEAO III-4 ia i?ieioa?aoeith oa aeaeeaaiiy A-eeioei, ui aecaaii noeioeyoei?th /a?ac CD40. Ciaeaeaii, ui neaiae /a?ac CD40 iiaeoeth? CD95-iiina?aaeeiaaiee aiiioic a iaoieia?/ieo ee?oeiao i?e o?ii?/iiio e?ioieaeeic?. Aeae?eai? 2 aa??aioe o?ii?/iiai e?ioieaeeico, i?e yeeo neaiaee /a?ac CD40 oa CD95 ? neia?a?/ieie aai aioaaii?noe/ieie. Aecia/ai? eiiiiiaioe neaiaeueieo oeyo?a, ye? aeoeaothoueny a A-ee?oeiao i?ney ia?aaea/? neaiaeo eiiiaoaioe?? /a?ac A-ee?oeiiee ?aoeaioi?. Oeaio?aeueiei eaioethaii oeeo eaneaae?a ? i?ioa?i oe?icei e?iaca Syk, yea anioe?eiaaia c i?ioa?i oe?icei e?iacith Lyn, PLC(1/2 oa na?ei/o?aii?i e?iacith PKC(. Anoaiiaeaii, ui ia i?ci?o aoaiao aeic??aaiiy A-ee?oei neaiae /a?ac CDw150 ? neia?a?/iei c CD95-iiina?aaeeiaaiei aiiioicii. Oeae iiaeoethth/ee aoaeo iiiieeiiaeueieo aioeo?e ?II-3 iiaea aooe aeei?enoaii aeey ?aaoethaaiiy aeeoa?aioe?thaaiiy oa aiiioico a ee?oeiao, ui eiaeni?anothoue ND95 oa CDw150. Iieacaii, ui iiiieeiiaeuei? aioeo?ea III-10 ?iciiciathoue iieiii?oio aeaoa?iiiaioo HLA-DR, aeni?aniy yei? ia ii?iaeueieo oa iooeeiieo ee?oeiao aiae?iciy?oueny aiae iiiiii?oieo aeaoa?iiiaio. Iiiieeiiaeuei? aioeo?ea ?II-10 iathoue aaaeeeaa ae?aaiinoe/ia cia/aiiy: ca aeiiiiiaith oeeo aioeo?e aeaeieaii iiaeaa?iaioe aino?iai e?ioiaeanoiiai eaeeico oa o?ii?/iiai e?ioieaeeico A-ee?oeiiiai iioiaeaeaiiy. Aeiaaaeaii, ui iiiieeiiaeuei? aioeo?ea III-24 aeyaeythoue CD37 aioeaai. Aeni?aniy ND37 aioeaaio oieueee ia c?ieeo A-eeioeiao iaoiiaeth? aeei?enoaiiy iiiieeiiaeueieo aioeo?e III-24 aeey aeeoa?aioeiaeueii? ae?aaiinoeee ? eeaneoieaoei? eaeeic?a oa e?ioii, a oaeiae ?ioiioa?ai?? iaaiaeaee?inueeeo ceiye?nieo e?ioii.. Ca aeiiiiiaith iiiieeiiaeueieo aioeo?e na??? ?II c’yniaai? nooo?a? iaoai?cie ?aaoeyoe?? aeoeaaoe??, aeeoa?aioe?thaaiiy oa aiiioico e?iaioai?ieo ee?oei, ui ia? aaaeeeaa cia/aiiy aeey ooiaeaiaioaeueii? a?ieia??, iieieia??, oa ?ioiieia??. IA?AE?E INIIAIEO IIOAE?EIAAIEO IAOEIAEO I?AOeUe CA OAIITH AeENA?OAOe?? Eiioiioeeoioeiey e iiiieeiiaeueiua aioeoaea a iieiaaiaoieiaee / Iei/oe A.A., Aeociai Ae.O. , Iaaeai?iay A.A., Neaei?aiei N.I., Aa?aiaiei E.A., Aanaaueaaa A.E., Aa?aeiaa A.A. / Iiae ?aae. A.A.Iei/oea. - E.: Iaoeiaa Aeoiea, 1990. - 232 n. Sidorenko S.P. CDw150 cluster report // Leucocyte Typing VI. - New York-London: Garland Publishing Inc. - 1997. - P. 582-584. Sidorenko S.P. CDw150 // Protein Reviews On The Web. - http://www.ncbi.nlm.nih.gov/prow/cd/cdw150.htm - 1997. - 4 ?. Neaei?aiei N.I. Fas/CD95-iiin?aaeoaiue aiiioic a iaoiaaiaca eeioieaeiuo iiaiia?aciaaiee // Yenia?ei.iieieiaey. - 1998. - O. 20, ?1. - N. 15-28. Ceaei?aiei N.I. Iiaa?oiinoiua aioeaaiu eeaoie /aeiaaea, nenoaiaoece?iaaiiua Iaaeaeoia?iaeiuie ?aai/eie niaauaieyie ii aeeooa?aioee?iai/iui aioeaaiai eaeeioeeoia /aeiaaea // ?ioiieia?y oa aea?aieia?y. - 1998. - O. 1, ?3. - N. 16-38. Iei/oe A.A., Neaei?aiei N.I., Aao?iaa A.I., Aa?aeiaa A.A., Oeaiaoeeay E.I., Aeociai Ae.O. Iiiieeiiaeueiua aioeoaea e eeaoeai eeioiaeanoieae-iie eeiee RPMI-1788 // Yenia?ei.iieieiaey. - 1986. - O. 8, ?6. - N. 41-46. Aeociai Ae.O., Neey?aiei E.I., Iaaeai?iay A.A., Iieoaeiaiei E.TH., Neaei?aiei N.I. ?aoeaioi?u iiaa?oiinoiuo iaia?ai, aeeooa?aioee?iai/iua aioeaaiu e oeeoioeie/aneea i?eciaee eeaoie e?iae i?e ino?ii eeioiaeano-iii eaeeica o aeaoae // Yenia?ei.iieieiaey. - 1987. - O. 9, ?3. - N. 36-39. Aao?iaa A.I., Neaei?aiei N.I., Aanaaueaaa A.E., Aa?aeiaa A.A., Oeaiaoeeay E.I., Aeociai Ae.O., Iei/oe A.A. Iiiieeiiaeueiua aioeoaea EII-3 i?ioea aioeaaia A-aeanoia /aeiaaea // Aeioaoiieiaey. - 1987. - O. 3, ?6. - N. 738-742. Neaei?aiei N.I., Aeociai Ae.O., Aao?iaa A.I., TH?/aiei I.A., Aa?aeiaa A.A., Oeaiaoeeay E.I., Iei/oe A.A. Oeeoioeie/aneia e yeaeo?iiii-iee?ineiie/aneia enneaaeiaaiea eeaoie iuoeiuo aea?eaeii // Oeeoieiaey - 1988. - O. 30, ? 1. - N. 39-44. Aa?aiaiei E.A., Aeociai Ae.O., Neaei?aiei N.I., Aao?iaa A.I., Aa?uoieeia A.TH., Oeeaoia A.A., Aa/o?ei I.N., Naa?nothe A.A. Ii?aaeaeaiea noaiiioeyoeee ii?iaeueiuo e ceiea/anoaaiii o?ainoi?ie?iaaiiuo eeioioeeoia a iaceao e?iae eiioiioa?iaioaoeaiui aenoioeie/aneei iaoiaeii n eniieueciaaieai iiiieeiiaeueiuo aioeoae // Yenia?ei.iieieiaey. - 1988. - O. 10, ?2. - N. 43-46. Neaei?aiei N.I., Aao?iaa A.I., Aa?aeiaa A.A., Oeaiaoeeay E.I., Aanaaueaaa A.E., Aeociai Ae.O., Iei/oe A.A. Iiiieeiiaeueiua aioeoaea EII-10 e aeeooa?aioee?iai/iiio aioeaaio A-eeioioeeoia /aeiaaea // Yenia?ei.iieieiaey. - 1988. - O. 10, ?3. - N. 42-44. Pinchouk, V.G., S.P. Sidorenko, D.F. Gluzman, E.P. Vetrova, A.G. Berdova, L.N. Shlapatskaya. Monoclonal antibodies IPO-3 and IPO-10 against human B cell differentiation antigens // Anticancer Res. - 1988. - V. 8, N5. - P. 1377-1380. I?i/oe A.A., Aeociai Ae.O., Neaei?aiei N.I., A?o?iaa A.I. Iiiieeiiaeue-i? aioeo?ea aenieiniaoeeo?/i? ?aaaaioe aeey ae?aaiinoeee iooeeiieo caoai-?thaaiue e?iaioai?ii? oeaieie /// A?ni. AI O?N?. - 1988 - ? 6.- N. 33-38. Aeociai Ae.O., Neaei?aiei N.I., Aa?aeiaa A.A., Aa?aiaiei E.A., Neey?aiei E.I., Iaaeai?iay A.A., Iieoaeiaiei E.TH., Ae?icaeiaa A.Ae. Eiioiioeeoioeie/aneea iaoiaeu n eniieueciaaieai iiiieeiiaeueiuo aioeoae e eaeoeiia a aeeaaiinoeea eeioiaeanoiiai eaeeica o aeaoae // Aaiaoie. O?ainooceie. - 1989. - O. 34, ?9. - N.20-23. Neaei?aiei N.I., Aa?aeiaa A.A., Aao?iaa A.I., Oeaiaoeeay E.I., TH?/aiei I.A., Aanaaueaaa A.E., Aeociai Ae.O. Iiiieeiiaeueiua aioeoaea EII-4, ?aniiciathuea aioeaai aeoeae?iaaiiuo O- e A-eeioioeeoia /aeiaaea // Yenia?ei.iieieiaey. - 1990. - O. 12, ?3. - N. 21-24. Neaei?aiei N.I., Aa?aeiaa A.A., Aao?iaa A.I., Oeaiaoeeay E.I., TH?/aiei I.A., Aeociai Ae.O. Iiiieeiiaeueiua aioeoaea na?ee EII a eco/aiee e aeeaaiinoeea ceiea/anoaaiiuo eeioii?ieeoa?aoeaiuo caaieaaaiee // Aaiaoie. O?ainooceie. - 1990. - O. 35, ?4. - N.19-22. Aa?aeiaa A.A., Neaei?aiei N.I., TH?/aiei I.A., Aao?iaa A.I., Oeaiaoeeay E.I., Aeociai Ae.O. Eiioiioaiioeie/aneay, oeeoioeie/aneay e oeueo?ano?oeoo?iay oa?aeoa?enoeea eeiee ceiea/anoaaiii o?ainoi?ie?iaaiiuo eeaoie /aeiaaea // Yenia?ei.iieieiaey. - 1991. - O. 13, ?3. - N.29-34. Sidorenko, S.P., Vetrova E.P., Yurchenko O.V., Berdova A.G., Shlapatskaya L.N., Gluzman D.F. Monoclonal antibodies of IPO series against B cell differentiation antigens in leukemia and lymphoma immunophenotyping // Neoplasma. - 1992. - V.39, N1. - P. 3-9. Sidorenko, S.P., Clark E.A.. Characterization of a cell surface glycoprotein IPO-3, expressed on activated human T and B lymphocytes // J. Immunol. -1993. - V.151, N9. - P. 4614-4624. Law C.-L., Sidorenko S.P., Chandran K.A., Draves K.E., Chan A.C., Weiss A., Edelhoff S., Disteche C.M., Clark E.A.. Molecular cloning of human Syk, a B cell protein tyrosine kinase associated with the sIgM/B cell receptor complex // J. Biol. Chem. - 1994. - V. 269, N 16. - P. 12310-12319. Neaei?aiei N.I., Oeaiaoeeay E.I., Aao?iaa A.I., Aa?aeiaa A.A., TH?/aiei I.A., Eeaiiaa O.O., Ieoaeai N.A., Aa?aiaiei E.A., Aeociai Ae.O. Iiiieeiiaeueiua aioeoaea EII-38 e yaea?iiio aioeaaio i?ieeoa?e-?othueo eeaoie // Yenia?ei.iieieiaey. - 1994. - O. 16, ?2-3. - N.145-150. Clark E.A., Berberich I., Klaus S.J., Law C.-L., Sidorenko S.P. Accessory molecules which influence signaling through B lymphocyte antigen receptors // Mechanisms of Lymphocyte Activation and Immune Regulation V. - New York: Plenum Press. -1994. - V. 365. - P. 35-43. Law C.-L., Sidorenko S.P., Clark E.A. Regulation of lymphocyte activation by the cell surface molecule CD22 // Immunology Today. - 1994. - V. 15, N 9. - P.442-449. Sidorenko S.P., Clark E.A. Activation panel mAb IPO-3 recognizes a novel activation marker of T and B lymphocytes // Leucocyte Typing V. - Oxford: Oxford University Press. - 1995. - V. I. - P. 1160-1662. Sidorenko, S.P., K.A. Chandran, Clark E.A. Identification of antigens associated with protein kinases by Activation panel mAb // Leucocyte Typing V. - Oxford: Oxford University Press. - 1995. - V. I. - P.1175-1177. Sidorenko S.P., Law C.-L., Chandran K.A., Clark E.A. Human spleen tyrosine kinase, p72Syk, associates with the Src-family kinase p53/56Lyn and a 120 kDa phosphoprotein // Proc. Natl. Acad. Sci.. - 1995. - V. 92, N 1275. - P. 359-363. Law C.-L., Sidorenko S.P., Chandran K.A., Zhao Z., Fisher E.H., Clark E.A.. CD22 associates with protein tyrosine phosphatase 1C, Syk, and phospholipase C-(1 upon B cell activation // J. Exp. Med. - 1996. - V. 183, N 2. - P. 547-560. Law C.-L., Chandran K.A., Sidorenko S.P., Clark E.A. Phospholipase Cg1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk // Mol. Cell. Biol. - 1996. - V. 16, N 4. - P. 1305-1315. Klaus S. J., Sidorenko S.P., Clark E.A.. CD45 ligation induces programmed cell death in T and B lymphocytes // J. Immunol. - 1996. - V. 156, N 8. - P. 2743-2753. Polacino P.S., Pinchuk L.M., Sidorenko S.P., Clark E.A. Immunodeficiency virus cDNA synthesis is regulated by T cell activation signals and dendritic cells // J. Med. Primatol. - 1996. - V. 25, N 3. - P. 201-209. Sidorenko S.P., Law C.-L., Klaus S.J., Chandran K.A., Takata M., Kurosaki T., Clark E.A. Protein kinase C mu (PKCm) associates with the B cell receptor and regulates lymphocyte signaling // Immunity. - 1996. - V. 5, N 4. - P. 353-363. Law C.-L., Craxton A., Otipoby K.L., Sidorenko S.P., Klaus S.J., Clark E.A. Regulation of signaling through B lymphocyte antigen receptors by cell-cell interaction molecules // Immunolological Reviews. -1996. - V. 153. P. 123-154. Rokhlin O.W., Bishop G.A., Hostager B.S., Waldschmodt T.J., Sidorenko S.P., Pavloff N., Kiefer M.C., Umansky S.R., Glover R.A., Cohen M.B. Fas-mediated apoptosis in human prostatic carcinoma cell lines // Cancer Res. - 1997. - V. 57, N 9. - P. 1758-1768. Rokhlin O.W., Hostager B.S., Bishop G.A., Sidorenko S.P., Glover R.A., Gudkov A.V., Cohen M.B. Dominant nature of the resistance to Fas- and tumor necrosis factor-alpha-mediated apoptosis in human prostatic carcinoma cell lines // Cancer Res. - 1997. - V. 57, N 18. - P. 3941-3953. Sidorenko, S.P., G. Shu, K.E. Draves, L.M. Pinchuk, S.V. Mikhalap, Z. Zhao, and E.A. Clark. The IPO-3/SLAM surface molecule associates with protein kinase activities and CD45 in B lymphocytes // Leucocyte Typing VI. - New York-London: Garland Publishing Inc. - 1997. - P. 584-585. Mikhalap S.V., L.N. Shlapatskaya, O.V. Yurchenko, A.G. Berdova, D.F. Gluzman, and S.P. Sidorenko. Monoclonal antibody IPO-38 recognizes a novel nuclear antigen of proliferating cells // Leucocyte Typing VI. - New York-London: Garland Publishing Inc. - 1997. - P. 609-610. A.n. 1389284 NNN?, IEE N 12 N 5/00, A 61 K 39/00. Ooaii aea?eaeiuo eoeueoeae?oaiuo eeaoie aeeaioiuo Mus Musculus, eniieuecoaiue aeey iieo/aiey iiiieeiiaeueiuo aioeoae e aeeooa?aioee?iai/iiio aioeaaio A-eeioioeeoia /aeiaaea / Aao?iaa A.I., Neaei?aiei N.I. (NNN?). - ? 4145194; Cayaeaii 03.09.86; Iioae. 15.12.87, AeNI - 6 n. A.n. 1420020 NNN?, IEE N 12 N 5/00, A 61 E 39/395. Ooaii aea?eaeiuo eoeueoeae?oaiuo eeaoie aeeaioiuo Mus Musculus, eniieuecoaiue aeey iieo/aiey iiiieeiiaeueiuo aioeoae e aeeooa?aioee?iai/iiio aioeaaio A-eeioioeeoia /aeiaaea / Neaei?aiei N.I., Aao?iaa A.I. (NNN?). - ? 4701376/31-13; Cayaeaii 25.02.87; Iioae. 30.08.88, Athe. ? 32. - 6 n. A.n. 1684338 NNN?, IEE N 12 N 5/18. Ooaii aea?eaeiuo eoeueoeae?oaiuo eeaoie aeeaioiuo Mus Musculus L - i?iaeooeaio iiiieeiiaeueiuo aioeoae e aeeooa?aioee?iai/iiio aioeaaio eeioioeeoia /aeiaaea / Neaei?aiei N.I., Aao?iaa A.I., Aa?aeiaa A.A., Oeaiaoeeay E.I. (NNN?). - ? 4711511/13; Cayaeaii 29.06.89; Iioae. 15.10.91, Athe. ? 38. - 6 n. A.n. 1705343 NNN?, IEE N 12 N 5/18. Ooaii aea?eaeiuo eoeueoeae?oaiuo eeaoie aeeaioiuo Mus Musculus L - i?iaeooeaio iiiieei-iaeueiuo aioeoae e aeeooa?aioee?iai/iiio aioeaaio (-eeioioeeoia /aeiaaea / Neaei?aiei N.I., Aao?iaa A.I., Oeaiaoeeay E.I., Aa?aeiaa A.A. (NNN?). - ? 4780344/13; Cayaeaii 08.01.90; Iioae. 15.01.92, Athe. ? 2. - 6 n. Neaei?aiei N.I., Aao?iaa A.I., Aa?aeiaa A.A., Aeociai Ae.O. Iieo/aiea e oa?aeoa?enoeea aea?eaeii, i?iaeooee?othueo iiiieeiiaeueiua aioeoaea e aeeooa?aioee?iai/iui aioeaaiai eeioioeeoia /aeiaaea // ?ieue eiioiiie nenoaiu a iaoiaaiaca eeioii?ieeoa?aoeaiuo caaieaaaiee. - Iiaineae?ne: Iaoea. - 1984. - N. 61-64. AIIOAOe?ss Neaei?aiei N.I. Iia? iiaa?oiaa? aioeaaie ee?oei, ui aeyaeythoueny iiiieeiiaeueieie aioeo?eaie na??? ?II, i?e eaeeicao oa e?ioiiao. - ?oeiien. Aeena?oaoe?y ia caeiaoooy iaoeiaiai nooiaiy aeieoi?a a?ieia?/ieo iaoe ca niaoe?aeuei?noth 14.01.07 - iieieia?y.- ?inoeooo aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i. ?.?. Eaaaoeueeiai IAI Oe?a?ie, Oe?a?inueeee iaoeiai-aeine?aeiee ?inoeooo iieieia?? oa ?aae?ieia?? IIC Oe?a?ie, Ee?a, 1998. Aeena?oaoe?th i?enay/aii i?iaeai? oaeineiiaeaiiy ?ioiioaiioeioaaiiy e?ioi?aeieo ee?oei c iaoith i?aeaeuaiiy aoaeoeaiino? aeeoa?aioe?aeueii? ae?aaiinoeee, eeaneo?eaoe?? oa ?ioiioa?ai?? eaeeic?a oa e?ioii ethaeeie. A ?iaio? ?icaeaa?oueny iiaee iai?yiie a iieiaaiaoieia??, yeee a?oioo?oueny ia ?aaoethaaii? aeeoa?aioe?thaaiiy oa aiiioico ceiye?nii o?ainoi?iiaaieo ee?oei /a?ac iiaa?oiaa? ?aoeaioi?e. Coai?aia ia?oa aio/eciyia iaiaeue iiiieeiiaeueieo aioeoie (IEAO) i?ioe aioeaai?a aeeoa?aioeithaaiiy eiioioeeoia ethaeeie. Aeyaeaii iiaee aioeaai CDw150. Becia/aia aeni?an?y, no?oeoo?a oa ooieoe?? CDw150, iieacaia eiai ?ieue o ?aaoeyoe?? aeeoa?aioe?thaaiiy oa aiiioico. Aia?oa io?eiai? IEAO ?II-4 aei aioeaaio ND95. Aea/aia aeni?an?y oeueiai aioeaaia a ii?i? ? i?e e?ioi?aeieo oi?iao eaeeic?a oa e?ioii. Ciaeaeaii, ui neaiae /a?ac CD40 iiaeoeth? CD95-iiina?aaeeiaaiee aiiioic a A-ee?oeiao a ii?i? oa i?e o?ii?/iiio e?ioieaeeic?. Iieacaii, ui IEAO ?II-10 ?ici?ciathoue iie?ii?oio aeaoa?i?iaioo HLA-DR, a IEAO ?II-24 aeyaeythoue ND37. Aecia/aia aeni?an?y oeeo aioeaai?a i?e eaeeicao oa e?ioiiao. Ca aeiiiiiaith IEAO na??? ?II aeae?eai? i?aeaa??aioe A-I aino?iai e?ioiaeanoiiai eaeeico oa A-ee?oeiiiai o?ii?/iiai e?ioieaeeico, anoaiiaeai? oaiioei?/i? iniaeeaino? iooeeiieo ee?oei i?e aieinaoiee?oeiiiio eaeeic? oa iaaiaeaee?inueeeo ceiye?nieo e?ioiiao. IEAO na??? ?II cai?iiiiiaai? aeey aeei?enoaiiy o ?ioiioaiioeioaaii?, ae?aaiinoeoe?, eeaneoieaoei? oa ?ioiioa?ai?? iooeeiieo caoai?thaaiue e?iaioai?ii? oeaieie. Eeth/ia? neiaa: iiaa?oiaa? aioeaaie ee?oei, CDw150, CD95, HLA-DR, CD37, aiiioic, eaeeice, e?ioiie. AIIIOAOeEss Neaei?aiei N.I. Iiaua iiaa?oiinoiua aioeaaiu eeaoie, auyaeyaiua iiiieeiiaeueiuie aioeoaeaie na?ee EII, i?e eaeeicao e eeioiiao. - ?oeiienue. Aeena?oaoeey ia nieneaiea o/aiie noaiaie aeieoi?a aeieiae/aneeo iaoe ii niaoeeaeueiinoe 14.01.07 - iieieiaey.- Einoeooo yenia?eiaioaeueiie iaoieiaee, iieieiaee e ?aaeeiaeieiaee ei. ?.A. Eaaaoeeiai IAI Oe?aeiu, Oe?aeineee iao/ii-enneaaeiaaoaeueneee einoeooo iieieiaee e ?aaeeieiaee IC Oe?aeiu, Eeaa, 1998. Aeena?oaoeey iinayuaia i?iaeaia oniaa?oainoaiaaiey eiioii-oaiioeie?iaaiey eeioieaeiuo eeaoie n oeaeueth iiauoaiey yooaeoeaiinoe aeeoa?aioeeaeueiie aeeaaiinoeee, eeanneoeeaoeee e eiioiioa?aiee eaeeicia e eeioii /aeiaaea. A ?aaioa ?acaeaaaony iiaia iai?aaeaiea a iieiaaiaoieiaee, iniiaaiiia ia ?aaoee?iaaiee aeeooa?aioee?iaee e aiiioica ceiea/anoaaiii o?ainoi?ie?iaaiiuo eeaoie /a?ac iiaa?oiinoiua ?aoeaioi?u. Cicaeaia ia?aay ioa/anoaaiiay iaiaeue iiiieeiiaeueiuo aioeoae i?ioea aeeooa?aioee?iai/iuo aioeaaiia eeioioeeoia /aeiaaea. Auyaeai iiaue aioeaai CDw150. Onoaiiaeaiu yeni?anney, no?oeoo?a e ooieoeee CDw150, e iieacaia aai ?ieue a ?aaoeyoeee aeeooa?aioee?iaee e aiiioica. Aia?aua iieo/aiu IEAO ?II-4 e aioeaaio ND95. Eco/aia yeni?anney yoiai aioeaaia a ii?ia e i?e eeioieaeieo oi?iao eaeeicia e eeioii. Iaia?oaeaii, /oi neaiae /a?ac CD40 iiaeoee?oao CD95-iiin?aaeiaaiiue aiiioic a A-eeaoeao a ii?ia e i?e o?iie/aneii eeioieaeeica. Iieacaii, /oi IEAO EII-10 ?aniiciatho iieeii?oioth aeaoa?ieiaioo HLA-DR, a IEAO EII-24 auyaeytho ND37. Onoaiiaeaia yeni?anney yoeo aioeaaiia i?e eaeeicao e eeioiiao. N iiiiuueth IEAO na?ee EII auaeaeaiu iiaeaa?eaiou A-I ino?iai eeioiaeanoiiai eaeeica e A-eeaoi/iiai o?iie/aneiai eeioieaeeica, onoaiiaeaiu oaiioeie/aneea iniaaiiinoe iiooieaauo eeaoie i?e aieinaoieeaoi/iii eaeeica e iaoiaeaeeeineeo ceiea/anoaaiiuo eeioiiao. IEAO na?ee EII i?aaeeiaeaii eniieueciaaoue aeey eiioiioaiioeie?iaaiey, aeeaaiinoeee, eeanneoeeaoeee e eiioiioa?aiee eaeeicia e eeioii. Eeth/aaua neiaa: iiaa?oiinoiua aioeaaiu eeaoie, CDw150, CD95, HLA-DR, CD37, aiiioic, eaeeicu, eeioiiu. SUMMARY Sidorenko S.P. New cell surface antigens detected by monoclonal antibodies of the IPO series in leukemia and lymphoma. - Manuscript. Thesis for a doctor’s degree by speciality 14.01.07 - oncology.- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of National Academy of Sciences of Ukraine, Institute of Oncology and Radiology Ministry of Health Care of Ukraine, Kyiv, 1998. The thesis is devoted to the problem of improving lymphocyte immunotyping, differential diagnosis, classification and immunotherapy of human leukemias and lymphomas. This work is a contribution to a new direction in oncohematology based on the regulation of malignant cell differentiation and apoptosis via cell surface receptors. The panel of monoclonal antibodies (mAb) against lymphocyte differentiation antigens was developed for the first time in Ukraine. The new antigen CDw150 was discovered. CDw150 expression, structure and functions were characterized. The role of this antigen in regulation of cell differentiation and apoptosis was shown. For the first time a mAb against CD95 was developed. CD95 expression was studied in normal lymphocytes and neoplastic cells in leukemias and lymphomas. It was shown that signal via CD40 modulates CD95-mediated apoptosis in normal and chronic lymphocytic leukemia B-cells. It was found that mAb IPO-10 recognizes the polymorph determinant of HLA-DR, and mAb IPO-24 is directed against CD37. Expression of these antigens on normal and leukemic cells was detected. Using mAbs of the IPO series, subvariants of B-I acute lymphoblastic leukemia and B-cell chronic lymphocytic leukemia were distinguished. Also, phenotypical characteristics of hairy cell leukemia and non-Hodgkin’s lymphomas were defined. MAbs of the IPO series were recommended for immunophenotyping, diagnosis, classification and immunotherapy of leukemias and lymphomas. Key words: surface cell antigens, CDw150, CD95, HLA-DR, CD37, apoptosis, leukemias, lymphomas. PAGE PAGE 10 PAGE 20

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