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1、LiebermanandMandelboim143THEROLEOFNKCELLSININNATEIMMUNITYNivaLiebermanandOferMandelboimLautenbergCenterforGeneralandTumorImmunology,TheHebrewUniversity,HadassahMedicalSchool,P.O.Box12272,Jerusalem91120,Israel.1.INTRODUCTIONNaturalkiller(NK)cellsarela
2、rgelymphocyteswithnumerouscytoplasmicgranulesthatarecapableoflysingtumorandvirusinfectedcells.TheydonotexpressTcellorBcellreceptors;rathertheyexpresstheCD56marker,whichenablestheirspecificidentification.NKcellsarefoundintheperipheralbloodandcompose5-
3、10%ofthetotallymphocytepopulation.Theycanbefoundinbloodandlymphoidtissuesespeciallythespleen(Abbasetal.,1994).Naturalkillercells,aswellascytotoxicTlymphocytes(CTL),aremajorcomponentofthecellularmechanismbywhichanimmuneresponseleadstothedestructionoff
4、oreignorinfectedtissue(Trinchieri,etal.,1989).IncontrasttoCTL,whichareactivatedinthepresenceofclassIMHCmoleculesandanappropriatespecificpeptide,NKcellspreferentiallylysetargetcellsdeficientinexpressionofMHCclassIproteins.InthismannerNKcellscarryoutim
5、munosurveillancefor‘missingself’,ratherthanfordirectdetectionofforeignantigens(Ljunggrenetal.,1990).NKcellsarepreventedfromkillinglymphoidcellsprimarilybyNKinhibitoryreceptorsthatarespecificforHLA-CandHLA-E(Leibsonetal.,1998).Whenactivated,theserecep
6、torssendinhibitorysignalstotheNKcellthatpreventlysisofthetargetcell.IncontrastthemajorityofCTLareactivatedbypeptidespresentedbyHLA-AandHLA-Bproteins(Littauaetal.,1991).LiebermanandMandelboim143Inthefirstpartofthisreviewwewilldescribetheworkperformedb
7、yCohenetal.(1999),showingthatthehumanImmunoDeficiencyVirus(HIV)developedmechanismsforabusingthispeculiarimmunesystembias.Usingthewellcharacterizedlymphoblastoidcellline721.221(221cells),thatdonotexpressHLA-A,-Bor–C.WepreparedHIV-1infected221celllines
8、transfectedwithgenesencodingforspecificallelesofHLA-A,-B–Cand-E.ThestrikingresultsofthisstudyshowthatHIV-1selectivelydownregulatesHLA-AandHLA-BbutdoesnotsignificantlyaffectHLA-CandHLA-E.ThisselectivedownregulationprobablyallowsHIVinfectedcellstoavoid
