Abstracts Vol. 1 [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Tu.A.375 - Tu.A.383
Tu.A.3 75
GENETIC DIVERSITY OF HIV- I IN THAILAND. 1994-95.

Tuesday, July 9, 1996

ftI AIJ) i Shitt i ' I I i i ni it I
S Li'tr i ti'.(d, ' i )ii I L)' X A
"3 rit it iii, I i i,. I ) p. )I fl d c l
OIibjective:L to (11 1 ine I iii-,'e ci h e
Methods: A iCri ('ii'is[aCple wsimd(
110)1e td A A 11 12 -1r ), M \Results: (AC-i I,,1 /'(31"B trins i cii s1i
FID iand / ( Ai'; i ' it i[)U B'.( IlyrI
Nor it i/Sn ai 'I i L ir~t p B vi sC'1
deteitrined.tArson,, LIst it ipi ' Bn I[
infec't itn, Ci ]ti f heL L ic r i it I,It
2F subtyptiiL adI/L-t' aq Ci csai 6,r
mos common iVS loo L I wi Ci i i if (w01i
sqCCC] m 'i )254f L tP(CF) / it tLi irow
that werei'iC tt / ii alyrcrt Cii I I rtt
spritfii o ut //ti EI ii B'.
Conclusions: Si'ueciii i i Lofdiadii
irix ofB' rrf E anicon LL[tt U fesCl
LU SA CiI t /,1"1 t 3) 12 37,Fax (. 1) Li i/

Ii iCAIA 'I I ADSi
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it > i /itp1 it i it IILSwpCrs,c y

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iiif ii C ' I

l s y ( fIA nI i /htL i L izrit i Liof C' t I I' B
'Li, ( E L ii Lf' fh i type C' B ii i r IfI ( i
II(- i, ll p for nit L L i h ii L yi t f ti
it Le(en i i L ici r 1(9cuPentAhisetho
att Lii B'. (' Ft vey.P eiC F LC theB
III iutypeLii' If ii ii Amngr sitypi/Ft F
tite lo; I I E t rFin s tif t CoulI rot
ci,I/L i( F e re t IN,) oii as. / F 2'e'IiiCA;t yp F / tLAnd i FVic 1i Lii' ( B FLAC 1'ci ri n
1Iitii' tt ii L tlanr ta, Le ciii M
Cieni a itL2a (iii ii

Z

Tu.A.380
HIV- I INFECTION ABOLISHES CD4-DEPENDENT CO-SIGNALLING VIA CD4/pS6 CF.
DISRUPTION AND INDUCES APOPTOSIS
(C intriitrun,i i iii I/ye,.. epririu tme t IIrinn t ed.~c i al i iof St.
Bi tt Lnit-F'. ptaril, Iii tir ite i fi~rr
Objective:]to r ''ti/u/i- i in ei pher i- ri t C/ti liBI-su-eefcr t if ecit/yILS'
iinfeit ii iiiiono i r i rii dii t rii e t, Ciiiv C CC' to/C It- iii i/it d Co- tiriti Cofithitt
CL I S it cllre-ctr (1 ("I co plex
Methods:IPBI-sweCc cuaturedr-Lti celrisolte C ItILS I ir_)adBF L)iLdth pLiC
rma fromi I ILV iI i i II r/ iii i ias((D _ r up 1 fi 1 ays i at i t 'i I ci nit ingi
lio io a tiC(.)f3 and I i (_)'1 t i t i i a d i f 'I C t ('C AVWr- p rd etriosC'~iC I / in C
firuiiFi tt/ p6 n AP C7O iCeite C m i itirt adsbjc erttoiCasriasiais aid
A'C'ti''rnilLot iii / Ly i r r onun tio, i it t Li ihspht ipiletic I i t - riatd PB]
tcrmirntlt c-xyr iiot/ltin Fcririto it -I irC'iti'LFI]D A Wtf ibcqientfoyCyto
riririi u/lyis.t(Lri'i' tt i'xprC'sin i i r ' itI byflaCCc/i tnnii
Results:Ilyrinr'LC it i/it i piLi'iiitinducedrtt/lrtti t t adC3 CD1I ii i I' Crc
Liroound l/ itroif -Lu iinitir'ly ine td clli Liii' it i it t (I)1ricptor cxpir'ssin 3/
forifcirch and Lifor nroi F'Ii. h tent i C'iiiC mti ikiafluri6C v it
tth( I/i C 'tor wasi hoIni-i heLisIriuptedi ILLS' i/i'ct itce llsw ihconidedi't h
Lii' ihibLit i i'iono h:cii ty ofi/ri / joyi n ii' iiu tyrCsie i C A l' AP-0 Cll ' I ga t iati i
t/C Fr/H Wi /2] ru r ['I IC iii _yr Ii i I i i, i t (),p,itC 3Cr Cii nifllowirnr
( Fl/ <it )1 i Lit C C.i i' ' s vir l iIi i CtI1r1 v r ifiec I c lsTI I-' ii u ed

Conclusions.: ittocontin HIS' by CD8+ T cells rn iivonmiy be retlited t
losif C//pr.. riii' envirmenit "maymodulate / D28 loss. iesuling'pin itss
if ti lifer it ii ' 'incytok Ani production, and loss of CD8+'CTL orothec protec tAiv me fI, r
FDiroth/ F. I. ' 1ir i anolCry Secion M929 DeBakey Buildirng, Brylr
Coleye of ]'t 'i /1 i>,, )iy o atzai Poatort.TX 77030. USA. 713) 798-6427 offce:
(/71 3 )79B-/9/C9 Fi
Tu.A.382
IL-2 RELIEVES SPONTANEOUS G I ARREST IN CD8+T-CELLS FROM HIV+ INDIVIDUALS
R.A.ICi CeniCE. i YPiA I', F I Donogbue. B.P Lowry. H.C. Lane. Nat italnitrutes of
H'ealth, NIAID, ( inic sand Lioleciular Betrorirology Section, Bethesda.,Liaryland 20892
Objectives: teri-iipheirit Iltod of HIS'infectedoindviduals iccunmulates ra ubpopulation
of CD.F8 ' T-c'li I/ut ire HI A DB+ird CD38+, During intermcitnent IL-2 therapy tbi
iiibpopiilain orfices dvisppears The purpose of the present study was to attempt t
better characterizc the-vaiousCD8+~subpopulaions that accumulate duing HIS'infec
ton and to dcinrutate ifhe cechantism r esponsible forciharges in theie subpoCpulaiorns
Methods: Periphi-iat blood mtonornuclear celIs were obtaired from HIS' and HIS'+ 'donrsc
ind sepatrated inttoF(DB+DR+ and CD8~ DR ftractions by immunom tgnet c Ibeadsdeparca
tion 01 FACS. FCel were iinilyzed by FAG S nd cultured with varrious IL-2 and PHA concentrations and exained I/ci:) proliferative responses with 3H-thym dire irn.orporastioni)
cell vaility usifg Pr tprdiuididne exclusior, and ii) cell cycle stage and ipoptosis usirg
sirmauttneouis DNA rcrtent and cell-surface immunoflu res ence analysis
Results: In additiii to DR- ad CD38+ tCD8 retls, CD8 ceLis that wer'e Fas '.CD'I5RD
[12R, CD57+, aid.DF2L were tiso'ibierved to accumulate during HIS'in/nction
Srmi lr to the n iv infdings ir paients witt'HIS' infection, CD8+DR+ cells from HIS'
dorirs could rot lbe s/imilatcd to pioliferate with IL-2+PHA and had a 26.20'~9.8i'i'les
suviveil irate nnrcilturc. Likewise, piifed CD8+~DR- celIs from HIS' donoirs simutated with
PHA alore iesulted r if heaacumulairon of DB~ cells that were smilai to the CD8+DR+
tnvio wth repcti/o prpensity to urdergo apoptoisi and showed ro pictiferaive cipaityTt'e addi/ii oo IL-2 to thes'e CD8+DR- cells resui/ed in high proliferative responses
Pr1elcimtry daita ising cornined celI cycle taaysis tnd cell sur'face antigen detection
r eseaied that celI. ft ro patiernti with HIS' infection had an increased pr opor tion of CD8+,
CD25+,~ CD57 antd LHLA DRC cells blocked i/ the G I /S phtse of the cell cycle.
Additrortally the C'D8+DR+ cells haid ii3'4 fold inctease of sub-G I DNA reltitre to
FCD8+DRuggetitgthat a portion of/the CD8+~DR+ were undergoing in eleevi/ed rite
of iipoptoiin ivo.C
Conclusions: HIS'in/Cc/ion is issoci/ted with a i/i/n of immune activation resaltirg in the
accurtlui/on Cf CD8.I~ IP'~cells that ire unable to be further expanded. Simir cells can
be gnrtdnvtotruhatvto fC8 cells rn an enviroinment lackng IL-2.These
celis expre s s ird Inc prone to apopti s This incr'eased i/ate of activation re/lects a celt
popuila/ion thait Liaicr/er eid /the G phase /f the celI cycle without transen re the G I S
check point. Adiis/itrtor of IL-2. in vivo or it vitro, prevents cells from becoming blocked
it G I/SThas. r addition to irducrng expirsion of CD4+ cells, IL-2 immunotherapy nay
atso iidiice C DB '-cellI tocint/nae through the cell cycle normally arnd ciiiry out proper
effeitor- function.
Richard A. Lempckr NHll.NIAID, CMiRS Bldg. IC. Rm. I B 13, 9000 Rockvileci Pke,
Bethteida, MD 20892-18/B
Tu.A.383
ASSOCIATION OF DYSREGULATED PRODUCTION OF IL-IO0WITH ALTERATIONS
IN THE CD28-B7 CO-STIMULATORY PATHWAY IN HIV INFECTION.
A Bumri.WD Crien y WF uneron,. I Diz-iiLitom r. L C.FI ron. Divisron ofVir'ology
CFldiren's Hospitl cf Fttern ntr/io, Dniversity of Dctawa, Dttawa, Drtario, Caiiada.
Objective: To stacy thte i/tenatiorns in the sgnats delivered by the costirulatory nolecule
CD2B in CD/+ T ce/Cs ard B7 receptors n ntonocy/ei/maciophages, ird its asioci/tion
with corstt/ively expressed immunoreguarttry cytoknei IL-tO in HIS' irfectior.
Methods: The expresio fCD28 on CDt4+ ird CD8+'T cells and B7-1 anci87-2ioForm itoni morocy'e fir12r 32 HIS'-infected amd S normiltindividuals mis aayzed by fBow
cytomietry CD4+~ cells were s/inuatied with an/i CD28 antihodiei and suboptimal concertaioar of PFHA(1:2//P.T celI prooh/eraion was cotrrelated with plaina virus toaid (p24) ad
the leve/i of IL-I10 produced by PBIA stimulated PBMC by using appiroptrite EL SA.
Alteraiorns in 872 expresion on CDLI4+ nono yteC /ollowing additior of ntonokines were
irvestigai/ed by flowuvyt0mw/uy
Results: CDI+ TcelIsCc/Fie F.D8+ T ccilIs, express normtltlevels of CD28 receptotrs but
fit to proliteratei /2ltowingp trausatrorwi/h ntitC.D28 antiodies compared to crtrols
in dicating signallintg defecIs at the level of the CD/B receptors Fur thermoreci CD28 induced
proliferai/ion wasisversely correli/cd with both plasma p24 levels and with the level of IL0 pr oduied by PH A s/nmuite/d PBMC Srne IL-10 s over expressed in HIS'+indivCdbaas

dawnim' e i t tin t/ 1E))
1/n IlS' t Li I iowCy
ciii-aed,(tic /r'ith cif
Conclusions: Fl irult
frth itt' I'] C C/tor
intciifered/ win/ h i Ci ii.i
ZAP 7/,iiipaliedi pec, alywdt prCirti
Feevr fo rtI Iinn/I it i/.
/BEH./iBe Ii. It/i16'1 B

i fIV IV lil
I t ftI B
Ito fti
ih f in si

) 7Cr tiririCC r u/i P ~pnedi i /ri -cctdcils
Ii )fCI (o. i i r i ii i'the I B rc i/t i/dh u'ay
In i'- r i'ic Ci /n pt is e11 Ic nth
/,~dCi ' si n tin if d iso i inm r f / i
'ti-Ct'VIn ito CioiLC~e(Iaialrt cc nils iyC- I]
'i 'Ci ir'liec Lib/ hi'lck ii Fr / ii io
ii lLi ihx t i/ n indt Liinofppti Thisthesci
1,r1 1Y i i Fi ii~ ih ' I/s of I nfLit/cr ttbi
de t 'Ifnd/ i ii in t/t l>r iC'

I Inn n n o; I y. Sil if rnti'' I IC C itt I_()rdci LFC IA

Tu.A.38 I
MECHANISMS OF CD8' T CELL DYSFUNCTION IN HIV
DLeiu SRi/rn t.YaFnk,. F lF cBnne/t tD. g/utpWS/toicr. Di'pmteitof
Mciii //i adiFrii ninioyBylrtilcc if icicinecI lt i rI /ULSAS
Objective: T/ xi'. iiin- rn' haI t i I Ci / CCC o/ c I n Li t Ci i //unctinairl ni iiur in/ic
o F FIB} -/ ll ' I ni l.- " iiiIll t iro r sc n
Methods: It/cnn /r/Cinaiycs viii fir urn//' ti'' fow / oerin/Iuni nut istu
Results:] ii tuirin if/bnrn unit/C u/of lB /1 cells hvC Ceii ICscitdiitin ii crc
inrgi uandi I Cp C CC i / ndlo F (31/ CF It mCi/i'e pro/CteF LI/h FI sB itpopultion in A ity u' /F IBD81 I i'll if Fo/C liri C in)fI ItS' i/tir nts rcvalCdI IC/it/gC ircatio ci-cur to'erf(CF/F /uel/nthels f/friroec tie 138DR+ Fitulttio
(r0fC/f nitaB'F c) iifcrc tteimrn/ tint ri/ri urniiur-Lur.FD2B (I=Lffht.A
tujrf ir//irtfr u/ctstt i / itactliiiC ^i<fro mul Iti12 ocnnrsiurnglV/To
detsr/Cnn r-i'fc'rnT2 /i iscrict (LI8 tiun i//i antunctut,Ce iin icitfe
efectio t i ) f / lBs.tILT I I ii Il/B it/isCr'ac -LpeitoCn and I i C iF n
CFIB1/icels/ C%F anredcethliri i/it/ riferaitei rsposetii ce'suntil
/1in. I/)s, /f / 28I /1 I rcdi C lhil i in to i ikCItC2 B'fir iiii ii'e C ce t iti r nit COP CI
Fir ofiC 8lB t / 'l r iILL / r's u.', it o ~C. [ tc ou/in /nt, ie' F...B, 'C t C i p im' I
whechr in -iit/Il /1/' sUL/t ii intl In po ceLitd~iffre t Li eAtl 1[-8~ 'iit rii
n/n t i n kIf LIII(-/c.I iiici I ifttf / f tcelsm' eCh1gh1 rn its f IL 2 (Ind ii'vrr
amourunts t/ If i' ll ih ' Brt)) m IC 1It. iii o I / 1

225