复旦大学课件T细胞亚群10-17

T细胞亚群何睿[e-mail]免疫学系上海医学院复旦大学ClassesoflymphocytesT细胞亚群T细胞活化分子机制T细胞免疫应答及其效应自身免疫和超敏反应TcellsubsetsTcellsandTcellsCD4+TcellsandCD8+TNaïveTcells（初始T细胞）EffectorTcells（效应T细胞）MemoryTcells（记忆T细胞）Thelper(Th)辅助性CD4+T细胞CytotoxicTcells(CTLs)细胞毒性CD8+T细胞RegulatoryTcells(Tregs)调节性CD4+T细胞TCellsubsetsClassFunctionsAntigenreceptorandspecificitySelectedmarkersPercentoftotallymphocytes(human)αβTlymphocytesBloodLymphnodeSpleenCD4+helperTlymphocytesBcelldifferentiation(humoralimmunity)Macrophageactivation(cell-mediatedimmunity)αβheterodimersDiversespecificitiesforpeptide-classIIMHCcomplexesCD3+,CD4+,CD8-50-60*50-6050-60CD8+cytotoxicTlymphocytesKillingofcellinfectedwithmicrobes,killingoftumorcellsαβheterodimersDiversespecificitiesforpeptide-classIMHCcomplexesCD3+,CD4-,CD8+20-2515-2010-15RegulatoryTcellsSuppressfunctionofotherTcells(regulationofimmuneresponses,maintenanceofself-tolerance)αβheterodimersCD3+,CD4+,CD25+(Mostcommon,butotherphenotypesaswell)Rare1010γδTlymphocytesHelperandcytotoxicfunctions(innateimmunity)γδheterodimersLimitedspecificitiesforpeptideandnonpeptideantigensCD3+,CD4,andCD8variableTcellsexpressalimitednumberofTCRsabundantinepithelialtissuesofcertainspecies:inthesmallbowelmucosaandintheskinofmouse.Intheskin,knownasadendriticepidermalTcell(DETC)donotrecognizeMHC-associatedpeptideantigensandarenotMHCrestricted.maybindtoconservedligandswhoseexpressionistriggeredbycellinjuryorstress,suchasmicrobialheatshockproteins.mayrepresentanimportantbridgebetweeninnateandadaptiveimmunity,functioningaslymphocytesthatenhancethefirstlineofdefenseagainstarangeofpathogens.Jensen,K.D.etal.ThymicselectiondeterminesTcelleffectorfate:antigen-naivecellsmakeinterleukin-17andantigen-experiencedcellsmakeinterferonImmunity29,90–100(2008).EpithelialTcellandPeripheralTcellCD27-IL-17+TcellsandCD27+IFN-+TcellsSubsetsofTcellsDevelopmentalprogrammingofTcellsubsets.CuaDJ,etal.NaturereviewImmunology,2010MartinBetal.IL-17-ProducingTcellsSelectivelyExpandinResponsetoPathogenProductsandEnvironmentalSignals.Immunity31,321–330(2009).TheyshowthatT-17cellsadditionallyexpressIL-23R,andtheinnatereceptorsTLR2anddectin-1,whichrecognizearchetypicalandfungalconstituents.TheseT-17cellsusethesereceptorstorapidlyproduceIL-17inresponsetobystandercell-derivedIL-23andtobacteriaandfungiwithoutconcomitantTCRstimulation.OneoftherolesofT-17-derivedmaybeindirectordirectamplificationofIL-17productioninTh17cells.Sutton,C.E.etal.Interleukin-1andIL-23induceinnateIL-17productionfromTcells,amplifyingTh17responsesandautoimmunity.Immunity31,331–341(2009).ThisreportshowsthatTcellshaveanearlyroleinpromotingCNSinflammation.Theauthorssuggestthatinnatecell-producedIL-17directlyenhancesdevelopmentofMOG-specificTh17cells.AmajorinnatesourceofIL-17InnateActivationofIL-17-ProductionbyaSpecializedTCellSubsetKapsenbergML.Immunity,2009Witherden,etal.ThejunctionaladhesionmoleculeJAMLisacostimulatoryreceptorforepithelialTcellactivation.Science2010SepIdentifyanepithelialTcells-specificcostimulatorymolecule,JAMLPetermannF,etal.TcellsenhanceautoimmunitybyrestrainingregulatoryTcellsresponsesviaanIL-23-dependengmechanism.Immunity,2010SepIL-23-activatedrendereffectorTcellsrefractorytothesuppressiveactivityofTregcellsandalsopreventedtheconversionofconventionalTcellsintoFoxp3+Tregcellsinvivo.TwonewpapersaboutTCellpublishedinthismonthNaïveTcellsMatureTcellsthathavenotpreviouslyencounteredantigen;Preferentialmigrationtosecondarylymphoidorgans(lymphnodes),wheretheyrecognizeantigenEffectorTcellsActivatedTcellscapableofperformingthefunctionsrequiredtoeliminateforeignantigensPreferentialmigrationtositesofinfectionorinflammationShort-livedMemoryTcellsLong-lived,functionallysilentcells;MountrapidsecondaryimmuneresponsestothesameantigenexposureHeterogenous(centralandeffector)BasedonthehistoryofantigenencounterandthestageofTcellactivation.NaiveTcellsEffectorTcellsMemoryTcellsMigrationPreferentiallytoperipherallymphoidtissuesPreferentiallytoinflamedtissuesPreferentiallytoinflamedtissues,mucosaltissuesFrequencyofcellsresponsivetoparticularantigenVerylowHighLowEffectorfunctionsNoneCytokinesecretion;cytotoxicactivityNoneCellcyclingNoYes+/-SurfaceproteinexpressionHigh-affinityIL-2receptorLowHighLowPeripherallymphnodehomingreceptor(L-selectin,CD62L)HighLowLoworvariableAdhesionmolecules:integrins,CD44LowHighHighChemokinereceptor:CCR7HighLowVariableMajorCD45isoform(humansonly)CD45RACD45ROCD45RO;variableMorphologySmall;scantcytoplasmLarge;morecytoplasmSmallCentralmemoryTcellsexpressCCR7andL-selectin,andhometolymphnodes.limitedcapacitytoperformeffectorfunctionswhentheyencounterantigengeneratemanyeffectorcellsuponantigenchallengeEffectormemoryTcellsdonotexpressCCR7orL-selectin,andhometoperipheraltissues,especiallymucosa.produceeffectorcytokinesuponantigenicstimulationdonotproliferatemuch.Basedontheirhomingpropertiesandeffectorfunctions.SubsetsofmemoryTcellsCD4+CD8+CD4+Th1-Th2hypothesis1986CoffmanandMossmanTh172006DiscoveryofCD4+Thce