Synergistic CD40 signaling on APCs and CD8 T cells drives efficient CD8 response and memory differentiation

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

关键词: immune responses;    effector functions;    CD4;    CD40–;    CD40L pathway;    aCD40ab administration;   

DOI  :  10.1189/jlb.0611292

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TheroleofCD4helpduringCD8responseandmemorydifferentiationhasbeenclearlydemonstratedindifferentexperimentalmodels.However,theexactmechanismsofCD4helpremainlargelyunknownandprecludereplacementtherapytodevelop.Interestingly,studieshaveshownthatadministrationofanagonistaCD40abcansubstituteCD4helpinvitroandinvivo,whereasthetargetsofthisantibodyremainelusive.Inthisstudy,weaddresstheexactroleofCD40expressiononAPCsandCD8TcellsusingaCD40abtreatmentinmice.WedemonstratethataCD40antibodieshavesynergeticeffectsonAPCsandCD8Tcells.FullefficiencyofaCD40treatmentrequiresCD40expressiononbothpopulations:ifoneofthesecellpopulationsisCD40‐deficient,theCD8Tcellresponseisimpaired.Mostimportantly,directCD40signalingonAPCsandCD8TcellsaffectsCD8Tcelldifferentiationdifferently.Inourmodel,CD40expressiononAPCsplaysanimportantbutdispensableroleonCD8Tcellexpansionandeffectorfunctionsduringtheearlyphaseoftheimmuneresponse.Conversely,CD40onCD8Tcellsiscrucialandnonredundantfortheirprogressivedifferentiationintomemorycells.Altogether,theseresultshighlightthatCD40–CD40L‐dependentandindependenteffectsofCD4helptodriveacompleteCD8Tcelldifferentiation...

【 授权许可】

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