Direct in vivo evidence of CD4+ T cell requirement for CTL response and memory via pMHC‐I targeting and CD40L signaling

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: dendritic cells;    antigen presentation;    immune response;    adaptive immunity;   

DOI  :  10.1189/jlb.1211631

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CD4+TcellhelpcontributescriticallytoDC‐inducedCD8+CTLimmunity.However,preciselyhowthesethreecellpopulationsinteractandhowCD4+TcellsignalsaredeliveredtoCD8+Tcellsinvivohavebeenunclear.Inthisstudy,wedevelopedanovel,two‐stepapproach,whereinCD4+Tcellsandantigen‐presentingDCsproductivelyengagedoneanotherinvivointheabsenceofcognateCD8+Tcells,afterwhich,weselectivelydepletedthepreviouslyengagedCD4+TcellsorDCsbeforeallowinginteractionsofeitherpopulationalonewithnaïveCD8+Tcells.ThisprotocolthusallowsustoclearlydocumenttheimportanceofCD4+T‐licensedDCsandDC‐primedCD4+TcellsinCTLimmunity.Here,weprovidedirectinvivoevidencethatprimedCD4+TcellsorlicensedDCscanstimulateCTLresponseandmemory,independentofDC‐CD4+Tcellclusters.OurresultssuggestthatprimedCD4+TcellswithacquiredpMHC‐IfromDCsrepresentcrucial“immuneintermediates”forrapidinductionofCTLresponsesandforfunctionalmemoryviaCD40Lsignaling.Importantly,intravital,two‐photonmicroscopyelegantlyprovideunequivocalinvivoevidencefordirectCD4‐CD8+TcellinteractionsviapMHC‐Iengagement.ThisstudycorroboratesthecoexistenceofdirectandindirectmechanismsofTcellhelpforaCTLresponseinnoninflammatorysituations.Thesedatasuggestanew“dynamicmodelofthree‐cellinteractions”forCTLimmunityderivedfromstimulationbydissociated,licensedDCs,primedCD4+Tcells,andDC‐CD4+Tcellclustersandmayhavesignificantimplicationsforautoimmunityandvaccinedesign...

【 授权许可】

CC BY