CD4_CD25_调节性T细胞的生物学特性及功能-CD4

CD4+CD25+T(,200011)R392A10002484X(2007)01200892041995SakaguchiCD4+CD25+T(Treg),TCD4+CD25+T:;(Anergy);CD4+TCD8+T;;,;CTLA24(Glucocorticoid2inducedtumornecrosisfactorreceptorfamily2relatedgeneGITR)[1,2]CD4+CD25+T1CD4+CD25+TregCD4+CD25+TregCD4+CD25-T,CD4+CD25+TregIL22R(CD25)IL22R(CD122)CTLA4(CD152)GITRCD44/CD45RB,50%HLA2DR80%CD45,TCRCTLA24[3],CD4+CD25+TregCD4+T5%10%CD25CD4+CD25+Treg,T,,CD25111CD4+CD25+TregCD4+CD25+Treg,Rafal[4],CD4+CD25+Treg,CD4+T,,TCRMHC2:(1972-),,,;:(1957-),,,,,E2mail:[e-mail][5],CD4+CD25+Treg,Seddon[6]CD4+CD25+Treg,CD4+CD25+TregCD4+CD25+TregMHC2,CD4+CD25+TregFoxp3,Foxp3naiveCD4+TFoxp3CD4+CD25+Treg,Foxp3CD4+CD25+Treg[7]112CD4+CD25+TregCD4+CD25+TregIL22(APC),IL22TCR,CD4+CD25+Treg(CD4+CD252T)TCD4+CD25+TregTCRCD4+CD8+TTCRCD3;,,,MHC,T[8]2CD4+CD25+Treg,3CD4+CD25+T,T;,CD25CD4+CD25+T;CD4+CD25+T98CD4+CD25+T1CD4+T,CD4+CD25+TCD4+CD25+TTCD4+CD25+TCD4+CD25-T,CD4+CD25-T,CD4+CD25+TT2TCD4+CD25-TIL212,CD4+CD25-T;CD4+CD25-TIL22,CD4+ThCD8+TCD4+CD25+TregT4(CTLA24,CD152),CD4+CD25+TregCTLA24,CD4+CD25+TregCTLA24[9211],CTLA24CD4+CD25+Treg,CTLA243CD4+CD25+Treg(TID)[12]T[13],T,[14],T,5%,T,,,TregT[13215]Sakaguchi[16]1995,naiveCD4+T10%CD25(IL22)CD25+CD4TT,;CD4+CD25+TCD4T,[17]CD4+CD25+TCD4+CD25+T,CD4+CD25+Treg,T/[18,19]3CD4+CD25+TSuri2PayerBALB/c,H/KATPCD4+T,CD4+CD25+TTh1/Th2,CD4+CD25+T,T,CD4+CD25+T,,4CD4+CD25+TregCD4+CD25+T[13]CD4+CD25+T,T,,CD4+CD25+T,;,TCD4+CD25+TT,[16]MLR,,CD4+CD25+TCD4+TCD8+T,IL22,CD4+CD25+T[19]CobboldCD4+CD25+T;CD4+CD25-T,CD4+CD25+T10CD4+T,,Th1Th2,CD4+CD25+T(Adoptivetransfer)[20]Naive,,T,CD4+CD25+TT,CD4+CD25+T,TT,,092007235CD4+CD25+Treg(GVHD)GVHD,CD4+CD25+T,CD4+CD25+TGVHDTaylor[21]CD4+CD25+TCD25+GVHD;CD4+CD25+TGVHD,GVHD,CD4+CD25+TCD4+T,CD4+CD25+TCD4+CD25+T,CD4+CD25+TGVHD,6CD4+CD25+TregTT,CD4+CD25+T,CD4+CD25+T,CD25CD4+CD25+TCD8+CD25+T,,CD4+CD25+T,23[22]CD25+;CTLA24,CTLA24T;CD4+CD25+TregCTLA24,T[22],CTLA24CD25CD4+CD25+Treg,7CD4+CD25+Treg2,CD4+CD25+T,,CD4+CD25+T,;CD4+CD25+T,[23],,B721/B722CD4+CD25+TCD4+CD25+T,,,CD4+CD25brightTreg,CTLA24,CD4+CD25brightTreg[24],CD4+CD25+T,,[25]CD4+CD25+T,CD4+CD25+T8CD4+CD25+TT,,,CD4+CD25+TCD4+CD25+T,,,GVHD91ShevachEM.Certifiedprofessionals:CD4+CD25+suppressorTcells[J].JExpMed,2001;193(11):F412F46.2ShimizuJ,YamazakiS,TakahashiTetal.StimulationofCD25+CD4+regulatoryTcellsthroughGITRbreaksimmunologicalself2tol2erance[J].NatImmunol,2002;3(2):1352142.3DetlefD,HediP,SusanneBetal.Exvivoisolationandcharacter219CD4+CD25+T1izationofCD4+CD25+Tcellswithregulatorypropertiesfromhumanblood[J].JExpMed,2001;193(11):130321310.4RafalP,PiofrK,LeszekI.PeptidespecificityofthymicselectionofCD4+CD25+Tcell[J].JImmunol,2002;168(2):6132620.5ModigilinY,CoutinhoA,PereiraPetal.Establishmentoftissue2specifictoleranceisdrivenbyregulatoryTcellsselectedbythymicepithelium[J].EurJImmunol,1996;26(8):180721815.6SeddonB,MasonD.PeripheralautoantigeninducesregulatoryTcellsthatpreventautoimmunity[J].JExpMed,1999;189(5):8772882.7PaiSY,TruittML,TingCNetal.CriticalrolesfortranscriptionfactorGATA23inthymocytedevelopment[J].Immunity,2003;19(6):8632875.8PiccirilloCA,ShevachEM.Cuttingedge:controlofCD8+TcellactivationbyCD4+CD25+immunoregulatorycells[J].JImmunol,2001;167(3):113721140.9DieckmannD,PlottnerH,BerchtoldS.Exvivoisolationandcharac2terizationofCD4+CD25+Tcellswithregulatorypropertiesfromhu2manblood[J].JExpMed,2001;193(11):130321310.10KingsleyCI,KarimM,BushellARetal.CD25+CD4+regulatoryTcellspreventgraftrejection:CTLA242andIL2102dependentimmu2noregulationofalloresponses[J].JImmunol,2002;168(3):108021086.11TakahashiT,TagamiT,YamazakiSetal.Immunologicself2toler2ancemaintainedbyCD25+CD4+regulatoryTcellsconstitutivelyexpressingcytotoxicTlymphocyte2associatedantigen4[J].JExpMed,2000;192(2):3032310.12BachJF,ChatenoudL.Tolerancetoisletautoantigensintypediabe2tes[J].AnnuRevImmunol,2001;19:1312161.13SakaguchiS.RegulatoryTcells:keycontrollersofimmunologicself2tolerance[J].Cell,2000;101(5):4552458.14ShevachE.RegulatoryTcellsinautoimmunity[J].AnnuRevIm2munol,2000;18:4232449.15MaloyKJ,PowrieF.RegulatoryTcellsinthecontrolofimmunepa2thology[J].NatImmunol,2001;2(9):8162822.16SakaguchiS,SakaguchiN,AsanoMetal.Immunologicself2toler2ancemaintainedbyactivatedTcellsexpressingIL22receptora2chains(CD25).Breackdownofsinglemechanismofself2tolerancecausesvariousautoimmunediseases[J].JImmunol,1995;155(3):115121164.17AsanoM,TodaM,SakaguchiNetal.AutoimmunediseaseasaconsequenceofdevelopmentalabnormalityofaTcellsubpopulation[J].JExpMed,1996;184(2):3872396.18ShevachEM,McHughRS,PiccirilloCAetal.ControlofTcellactivationbyCD4+CD25+suppressorTcells[J].ImmunolRev,2001;182:58267.19SakaguchiS,kaguchiN,ShimizuJetal.ImmunologictolerancemaintainedbyCD25+CD4+regulatoryTcells:theircommonroleincontrollingautoimmunity,tumorimmunity,andtransplantationtoler2ance[J].ImmunolRev,2001;182(8):18232.20ZelenikaD,AdamsE,HummSetal.TheroleofCD4+T2cellsub2setsindeterminingtransplantationrejectionortolerance[J].Immu2nolRev,2001;182(8):1642179.21TaylorPA,LeesCJ,BlazarBR.TheinfusionofexvivoactivatedandexpandedCD4+CD25+immuneregulatorycellsinhibitsgraft2ver2su