记忆性T细胞的形成-维持和功能

ChineseBulletinofLifeSciences22620106Vol.22,No.6Jun.,20101004-0374(2010)06-0506-092010-04-07(973)(2007CB512404)*E-mail:[e-mail](510080)TTTTTTR392.12AGeneration,maintenanceandfunctionofmemoryTcellsLIUYun,WUChang-you*(DepartmentofImmunology,ZhongshanSchoolofMedicine,SunYat-senUniversity,Guangzhou510080,China)Abstract:Immunologicalmemoryistheabilitytomakeasecondandmoreeffectiveimmuneresponsetoanantigenthatencounteredpreviously.AntigenisprocessedtoshortpeptidesandpresentedbyDCsonMHCmoleculestoinitiatetheresponsesofTcells.ATCRsignalwithco-stimulileadstoclonalexpansionofantigen-specificTcellsandfollowsaphaseofcontraction,inwhichmostshort-livedantigen-specificeffectorTcellsdie.Someofthesecellssurviveandformlong-livedmemorycells.Memorycellsareheterogeneousinphenotypeandfunction.UnderstandingthepropertiesofmemoryTcellswillhelpinthedesignofvaccinesandtheimmuno-therapyfordiseases.Keywords:Tcells;memory;cytokineThucydides19,507T,756540,BTT1T(naiveTcells)()(dendriticcell,DC)(majorhistocompatibilitycomplex,MHC)MHCCD4+CD8+TT(TCR)[1,2]LPSCpGdsRNATLRsDCCD40CD80CD86TCD154CD28CD152T[3,4]DC()TT2TTAPCT/APC/MHCTCRLCKLAKPCKT(cytotoxiclympho-cyte,CTL)T[5-7]CD4+CD8+T24hCD8+T7CD4+TCD4+TCD4+TCD8+T50%CD8+T10%CD4+T3T1~2TTT5%~10%[8,9]TT3.1T:TTTCD8+TTTReinerCD8+TT[10]OT-1-TCRTCRβTMDCD8+TCD8+TTTCRNF-κBCD8+TT[11]Wu[12]IFN-γ+TCRTgCD4+TIFN-γ-TCRTg508IFN-γTDCT(CD4+TIFN-γCD8+TGranzymeB)IFN-γ+CD4+TIFN-γ-CD4+T[13,14]TCD8+TIL-2Bcl-2CD62L3.2T3.2.1TCTL[15,16]LCMV5%~10%CTLCD8+TCTLDNACTLCTL3.2.2r-T-MHC()()PRRsIFNsIL-12IFN-γDCsCTLTT()IL-12IFN-γIFNsCD8+TIL-12Bcl-3CD8+T[17,18]IL-12-/-ListeriaCD8+TIL-12CD8+TT-bet[19,20];T-betKLRG1highIL-7RlowIFN-γIFN-γIL-7RIFN-γRCD8+T[21,22]IL-10CD8+TIL-1024hCD8+T[23]IL-10IL-10RCD8+TListeria[24]3.2.3r-TIL-7IL-15IL-7IL-7RTTIL-7RαCD8+TIL-7RIL-7CD8+TIL-7CD4+TIL-7-IL-7RCD4+T[25,26]Sun[27]IL-7TCRCD4+TBcl-2GM-CSF/IL-7RIL-7RLCMVIL-7IL-2CD8+TTIL-2IL-7IL-15CD8+T[28-30]IL-2IL-15KLRG1hiCD127loIL-7509TKLRG1loCD127hi3.2.4T-betId2Blimp-1TT-betTh1T-beteomesodermin(eomes)T-betCD8+TCD127CD8+TIL-12T-beteomesT-betKLRG1hiIL-7RloT-betKLRG1loIL-7RhiId2Id2CD8+T80%~90%Id2CD8+T[31]Blimp-1Blimp-1Id2Blimp-1Blimp-1TBlimp-1BTBcl-6Bcl-6CD8+TBcl-63.2.5TTTCD8+T[32,33]mTORmTORCD8+T[32,33]mTORT3.33.3.1BimFasBcl-2T[34]Bcl-2Bim+/-Bcl-2-/-TLCMV-CD4+TCD4+TBcl-2CD4+TBim(Bcl-2-interactingmediatorofdeath)BimTBim-/-Bim-CD4+TBimFas/Fas-LCD8+TLCMVMHVFasBim[35-38]3.3.2FOXO3aNoxaFOXO3aSTAT5aBimFasCD4+THIVFOXO3aCD4+TNoxaTBim1NoxaBim1CD4+TBim1-NoxaBim1CD4+TNoxa3.4T3.4.1CD8+T3.4.1.1CD8+TMHCIL-7IL-15[39-42]IL-7RCD8+TCD8+TIL-7CD8+TIL-7RIL-7RSTAT5Bcl-2Bcl-2IL-7STAT5Bcl-2IL-15CD8+T510CD8+TIL-7IL-15IL-7IL-15CD8+T,CD8+TBarber[43]CD8+TPD1(programmedcelldeath1)PD1CD8+TLCMVIL-10CD8+T[44,45]CD8+TCD8+TCD8+TIL-7IL-15CD8+T[46,47]CD8+TCD8+TCD8+TCD8+TCD8+TCD8+TCD8+T3.4.1.2CD4+TCD8+TCD4+TCD40/CD40LDCDCCD8+TCTL[48-50]LCMVHIVCD4+TCTLLPSCpGDNAdsDNAssRNADCCTLCD4+T,LCMV,VSVListeriaCD4+TCD8+T[51-53]Castellino[54]CD4+TDC,CD8+TCD8+TCD4+TCD8+TTRAILCD8+T[55]LCMVCD4+TTRAILCD8+T60dCD4+T()CD8+TIntlekofer[56]CD8+TT-betT-betCD4+TCD8+T(CD62LhiCCR7hi)T-betTRAILCD4+TCD8+TCD4+TCD8+TIFN-γIL-2IL-7RαCD62LCD122IL-2CD8+TIL-2R(CD25)CD8+T[57]IL-2CD8+TCD4+TCD8+T3.4.2CD4+T3.4.2.1CD4+TTCRCD4+TCD8+TCD4+TMHCIL-7IL-15[58,59]IL-7CD4+TIL-15IL-15(CD122)CD4+TCD8+TNKIL-15CD4+TCD8+TNK3.4.2.2TCRMHCIICD4+T511TCD4+TTCRMHCIIIL-7IL-15TCR-MHCCD4+TCD4+T4CD45TT(CD45RA+)T(CD45RA-);CD8TEMCD45RA(TEMRA)CD8+TCD27CTLCD27CD27CD8+T[60]T(centralmemorycells,TCM)(effectormemorycells,TEM)[61,62]TCMCD45ROCCR7CD62LTCMIL-2TTEMCD45ROCCR7CD62LTCMTEMTCRCD4+CD8+TIFN-γIL-4IL-5CD8TEMTEMTCMTCMTEM(1)TCMCCR7TCMTEM(2)(3)TEMTCMTEMTCMTCRTEMTCMTCMTEMTCMCXCR5TIL-2IL-10CD40LICOSBTEMTH1TH2CXCR3CCR4TH1TH2TEM(TH1TH2)TTTDCTTCLACCR4TTCCR9TTTCCR75:(1)CTLCTL(2)TT(1000)(3)(4)T,,TT2~3(5)TCD8+TIFN-γBCD8+TRNACD8+TCD8+T5126,,B,,TCD4+CD8+T[63,64]Th1CD4+TTh1Th1Th1CD8+TTh1CD8+TT90%T,T[65]T,,TTT,,T,[][1]BanchereauJ,SteinmanRM.Dendriticcellsandthecontrolofimmunity.Nature,1998,392(6673):245-52[2]HeathWR,CarboneFR.Cross-presentation,dendriticcells,toleranceandimmunity.AnnuRevImmunol,2001,19:47-64[3]PasareC,MedzhitovR.Toll-likereceptors:linkinginnateandadaptiveimmunity.AdvExpMedBiol,2005,560:11-8[4]KawaiT,AkiraS.Innateimmunerecognitionofviralinfection.NatImmunol,2006,7(2):131-7[5]MonksCR,FreibergBA,KupferH,etal.Threedimen-sionalsegregationofsupramolecularactivationclustersinTcells.Nature,1998,395(6697):82-6[6]GrakouiA,BromleySK,SumenC,etal.Theimmunologicalsynapse:amolecularmachinecontrollingTcellactivation.Science,1999,285(5425):221-7[7]LanzavecchiaA,SallustoF.DynamicsofTlymphocyteresponses:intermediates,effectors,andmemorycells.Science,2000,290(5489):92-7[8]LanzavecchiaA,SallustoF.Progressivedifferentiationandselectionofthefittestintheimmuneresponse.NatRevImmunol,2002,2:982-7[9]MasopustD,KaechSM,WherryEJ,etal.TheroleofprogramminginmemoryT-celldevelopment.CurrOpinImmunol,2004,16(2):217-25[10]ChangJT,PalanivelVR,KinjyoI,etal.AsymmetricTlym-phocytedivisionintheinitiationofadaptiveimmuneresponses.Science,2007,315(5819):1687-91[11]TeixeiroE,DanielsMA,HamiltonSE,etal.Di