T细胞亚群2014硕士

T细胞亚群何睿[e-mail]免疫学系上海医学院复旦大学T细胞亚群T细胞活化机制T细胞免疫应答及其效应PhasesofTcellresponsesprimingTcellsubsetsTcells(~95%)andTcells(~5%)CD4+TcellsandCD8+Tcells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,andCD8variablePositiveselectionNegativeselectionTcelldevelopmentinthethymusPhasesofTcellresponsespriming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.SubsetsofmemoryTcellsNatureImmunol,2011,June,thereviewsofmemoryTcellCD4+CD8+CD4+.EffectorTcellsubsetsTh1-Th2hypothesis1986CoffmanandMossmanTh172005Tfh2000DiscoveryofCD4+ThcellsubsetsHowtheyareinduced,WhatcytokinestheyproduceWhateffectormechanismstheyactivateTh0Th1Th2Th17HumoralImmunityImmunemodulationThesubsetsofCD4+ThcellsPropertiesofCD4+Th1andTh2subsetsCytokinesStimulithatinfluencethepatternofThcelldifferentiationTCRsignalstrengthDifferentsubsetsofdendriticcellsmayexistThegeneticmakeupofthehostSTAT:SignaltransducerandactivatoroftranscriptionDifferentiationofTh1SubsetStimulatedbyintracellularmicrobesthatinfectoractivatemacrophagesorNKcellsListeria,mycobacteriaandLeishmaniaImportantcytokinesfortheTh1differentiationImportanttranscriptionfactors(TF)fortheTh1differentiationIL-12IFN-IL-18typeIIFNs(inhuman)T-bet:masterregulatorSTAT4STAT1ThemolecularbasisofTh1differentiationTheinterplayofsignalsfromtheTcellreceptor,thecytokinesIFN-andIL-12,andtheTFT-bet,STAT1,andSTAT4IL-12STAT-4IFN-STAT-1AgrecognitionbyTCRT-betApositiveamplificationloopbetweenT-betandIFN-DifferentiationofTh2SubsetImportantTFfortheTh2differentiationStimulatedbymicrobesandantigensthatcausepersistentorrepeatedTcellstimulationwithlittleinflammationormacrophageactivationHelminthandallergensImportantcytokinesfortheTh2differentiationIL-4GATA-3:masterregulatorSTAT6ThemolecularbasisofTh2differentiationTheinterplayofsignalsfromtheTcellreceptor,thecytokineIL-4,andtheTFGATA-3andSTAT6Th2differentiationismostdependentonIL-4IL-4STAT-6AgrecognitionbyTCRGATA-3DevelopmentofTh1andTh2subsetsTh2celldifferentiationrequiresbothGATA3expressionandSTAT5activationNatureReviewImmunol,2010DifferentiationofTh17SubsetStimulatedbyzymosan,fungus,myobacteriaImportantcytokinesfortheTh17differentiationImportanttranscriptionfactors(TF)fortheTh17differentiationIL-6TGF-IL-23IL-21ROR-t:masterregulatorROR-STAT3AhRStepsinthedifferentiationofTh17cellsConventionalTh17celldevelopmentImmunologicReview,2013FollicularhelperTcells(TFH)PreferentiallyresidentinBcellfolliclesExpressCXCR5,aearlydefiningmarkerProducealargeamountofIL-21,whichactsinanautocrinemannertogetherwithIL-6promotetheirdifferentiationandexpansionDependontheBcl-6transcriptionfactorEs