Distinct Differences in the Expansion and Phenotype of TB10.4 Specific CD8 and CD4 T Cells after Infection with Mycobacterium tuberculosis 英文参考文献.docVIP

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Distinct Differences in the Expansion and Phenotype of TB10.4 Specific CD8 and CD4 T Cells after Infection with Mycobacterium tuberculosis 英文参考文献.doc

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Distinct Differences in the Expansion and Phenotype of TB10.4 Specific CD8 and CD4 T Cells after Infection with Mycobacterium tuberculosis 英文参考文献

DistinctDifferencesintheExpansionandPhenotypeof TB10.4SpecificCD8andCD4TCellsafterInfectionwith Mycobacteriumtuberculosis TrucThiKimThanhHoang1,AnnelineNansen2,SugataRoy1,RolfBilleskov1,ClausAagaard1 ,Tara Elvang1,JesDietrich1*,PeterAndersen1* 1DepartmentofInfectiousDiseaseImmunology,StatensSerumInstitut,Copenhagen,Denmark,2DepartmentofImmunopharmacology,NovoNordisk,Ma?l?v,Denmark Abstract Background: Recently we and others have identified CD8 and CD4 T cell epitopes within the highly expressed M. tuberculosisproteinTB10.4.Thishasenabled,forthefirsttime,acomparativestudyofthedynamicsandfunctionofCD4 andCD8TcellsspecificforepitopeswithinthesameproteininvariousstagesofTBinfection. MethodsandFindings:WefocusedonTcellsdirectedtotwoepitopesinTB10.4;theMHCclassIrestrictedepitopeTB10.4 3–11(CD8/10.4Tcells)andtheMHCclassIIrestrictedepitopeTB10.4 74–88(CD4/10.4Tcells).CD4/10.4andCD8/10.4Tcells displayedmarkeddifferencesintermsofexpansionandcontractioninamouseTBmodel.CD4/10.4Tcellsdominatedinthe earlyphaseofinfectionwhereasCD8/10.4Tcellswereexpandedafterweek16andreached5–8foldhighernumbersinthe latephaseofinfection.IntheearlyphaseofinfectionbothCD4/10.4andCD8/10.4Tcellswerecharacterizedby20–25% polyfunctionalcells(IL-2 ,IFN-c ,TNF-a+),butwhereasthemajorityofCD4/10.4TcellsweremaintainedaspolyfunctionalT cellsthroughoutinfection,CD8/10.4Tcellsdifferentiatedalmostexclusivelyintoeffectorcells(IFN-c+,TNF-a+).BothCD4/ 10.4andCD8/10.4Tcellsexhibitedcytotoxicityinvivointheearlyphaseofinfection,butwhereasCD4/10.4cellmediated cytotoxicitywanedduringtheinfection,CD8/10.4Tcellsexhibitedincreasingcytotoxicpotentialthroughouttheinfection. + + Conclusions/Significance:OurresultsshowthatCD4andCD8Tcellsdirectedtoepitopesinthesameantigendifferbothin theirkineticsandfunctionalcharacteristicsthroughoutaninfectionwithM.tuberculosis.Inaddition,theobservedstrong expansion of CD8 T cells in the late stages of infection could have implications for the development of post exposure vaccinesa