ThTh表面標志專題知識培訓課件

ThTh表面標志專題知識OutlineThcellsubsetsRoleofDCsindeterminingTcelleffectorfunctionFactorsnecessaryforTh1/2differentiationAnewThsubset-ThIL-17DevelopmentandfunctionofTreginperiphery2ThTh表面標志專題知識Na?veCD4+TcellscandifferentiateintoseveralTeffandTregtypes3ThTh表面標志專題知識Immunol.Rev.182:207,20014ThTh表面標志專題知識Th1/Th2/Th17indiseaseAgent/Disease Host Response OutcomeLeishmaniasis M Th1 Cure Th2 ExacerbationLeprosy H Th1 Tuberculoid Th2 LepromatousRA/MS H Th1 Th1cellsinlesion H Th17 Th17inlesions Allergy H Th2 Th2cytokinesin lesion M Th17 InducesPMNAcGVHD M Th1 Th1cytokinesChrGVHD M Th2 Th2cytokines5ThTh表面標志專題知識6ThTh表面標志專題知識NatureRev.Immunol.3:984,20037ThTh表面標志專題知識DendriticcellsandTcelleffectorfunction8ThTh表面標志專題知識Th1/Th2differentiationArisefromacommonprecursorCytokinesAntigendoseCostimulatorymoleculesDifferentiationresultsinexpressionofmasterregulators:GATA-3forTh2andT-betforTh19ThTh表面標志專題知識SignalingmoleculesandtranscriptionfactorsimportantinTh1/Th2differentiationAnnu.RevImmunol.21:713,200310ThTh表面標志專題知識KnockoutmicethathavedefectsinTh1development:IFN-,IFN-R,IL-12,IL-12R,Stat4,IRF-1,ICSBP,T-betIL-12isnecessaryforIFN-production,andIFN-isnecessaryfortheinductionofIL-12responsiveness(actsviainductionofT-bet)stimulatesexpressionoftheIL-12Rchain(signaltransduction)IL-4andIFN-aremutuallyantagonisticinTh1/Th2development

SourceofIL-12:dendriticcells,macrophages.CertainpathogensstimulatesecretionoflargeamountsofIL-12byDCandmacrophagesSourceofIFN-:NKcells,Th1cells11ThTh表面標志專題知識KnockoutmicethathavedefectsinTh2development:IL-4,IL-13,IL-4R,Stat6GATA-3antisenseblocksTh2developmentSourceofIL-4WasthoughttobeeithermastcellsorCD4+NK1.1+Tcells-butneitheronewasprovenNowthoughttocomefromdevelopingTh2cells-undertheinfluenceofIL-6,althoughIL-6KOmicecanstillmakesomeTh2responses.ItispossiblethatTh2differentiationisthedefaultpathwayintheabsenceofIL-1212ThTh表面標志專題知識CytokinesinfluenceTh1/Th2differentiationScience260:547,199313ThTh表面標志專題知識Interleukin420kDproteinproducedbyTh2cells,mastcells,NKTcellsInducesproliferationofTcellsanddifferentiationofTh2cells;antagonizesTh1differentiationInducestheexpressionofGATA-3transcriptionfactor14ThTh表面標志專題知識IL-4receptorAnnu.Rev.Immunol17:701,1999Stat615ThTh表面標志專題知識Interleukin-12HeterodimericcytokineIL-12p70-formedbytwochainsIL-12p40andIL-12p35(encodedondifferentchromosomes)ProducedbyactivatedDC,macrophagesActsonNKandTcellstostimulateIFN-production;costimulatesTh1proliferation;enhancesNKcytotoxicactivity;inducesTh1differentiationIL12-Rhastwochainsand2;signalsthroughstat4IL-12p40canformhomodimersandinhibittheactionofIL-12p7016ThTh表面標志專題知識17ThTh表面標志專題知識IL-12andIL-2318ThTh表面標志專題知識ThIL-17cellsProduceIL-17,IL-17F,IL-6,TNFIL-17inducestheproductionproinflammatorycytokines:TNF,IL-1,IL-6,IL-8ThIL-17cellshavebeenfoundinthediseasedtissuesofpatientswithRA,Lymearthritis,MS,SLEandasthmaNewdatasuggestthatthisisadistinctlineage-developmentmayrequireIL-6andTGF-

19ThTh表面標志專題知識CytokinerequirementsforThIL-17Nature44:235(2006)

20ThTh表面標志專題知識21ThTh表面標志專題知識RoleofDCsubsetsandantigendoseinthedifferentiationofTh1orTh2cellsJ.ExpMed.197:101.200323ThTh表面標志專題知識OthermoleculesimplicatedinTh1/Th2differentiationCostimulatorymolecules:CD86,B7-hbindtoCD28andICOSresp.OX40(Tcell)-OX40L(DC)-inducedafteractivation,favorTh2Chemokines-differentialexpressionofchemokinereceptorsofTcellsubsets,differentpatternsofchemokineproductionbyDCsubsets24ThTh表面標志專題知識NewdatasuggestthatOX40Lmayplayaroleininducinginflammatorycytokines(TNF)J.Exp.Med.202:1213.200525ThTh表面標志專題知識26ThTh表面標志專題知識27ThTh表面標志專題知識RegulatoryTcellsintheperipheryNaturallyoccurringCD4+CD25+Tregs;developinthymusTr1cells-produceIL-10;inducedfollowinginteractionwithDCinpresenceofimmunsuppressivecytokinesTh3cells-produceIL-10andTGF-b,usuallyfoundatmucosalsurfaces28ThTh表面標志專題知識29ThTh表面標志專題知識J.Immunol.171:6323,200330ThTh表面標志專題知識31ThTh表面標志專題知識32ThTh表面標志專題知識33ThTh表面標志專題知識MechanismsofSuppression34ThTh表面標志專題知識AlsoinducesFoxP3expressioninCD4+CD25-TcellsJI176:6752,