CD70 expression by dendritic cells plays a critical role in the immunogenicity of CD40‐independent, CD4+ T cell‐dependent, licensed CD8+ T cell responses

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

关键词: costimulation;    cell differentiation;    cell‐;    surface molecules;   

DOI  :  10.1189/jlb.0809535

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThestimulationofDCbyCD4+TcellsisknowntoconditionDCtoactivatenaïveCD8+Tcells,predominantlyviaCD40‐CD40Linteractions.IthasbeenproposedthatacriticalconsequenceofDCconditioningistheinductionofCD70expression.WhetherandhowCD70inductioncontributestoCD8+TcellresponsesintheabsenceofCD40‐CD40Linteractionsareunknown.CD8+Tcellresponsestoadenoviral‐orDC‐basedimmunizationofCD40‐deficientmicerevealedaCD40‐independent,CD4+Tcell‐dependentpathwayforCD70inductiononconventionalDC.ThispathwayandsubsequentCD8+Tcellresponseswereenhancedby,butnotdependenton,concomitantactivationofTLRandinpart,usedTRANCEandLIGHT/LTαβstimulation.BlockingTRANCEandLIGHT/LTαβduringstimulationreducedtheimmunogenicityofCD40‐deficientDC.ThesedatasupportthehypothesisthatinductionofCD70expressiononDCafteranencounterwithactivatedCD4+TcellsisamajorcomponentofCD4+Tcell‐mediatedlicensingofDC.Further,multiplepathwaysexistforCD4+TcellstoelicitCD70expressiononDC.ThesedatainpartexplainthecapacityofCD40‐deficientmicetomountCD8+TcellresponsesandmayprovideadditionaltargetsforimmunotherapyinsituationswhenCD40‐mediatedlicensingiscompromised...

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