Differential mechanisms of memory CD8 T cell maintenance by individual myeloid cell types

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

关键词: homeostasis;    dendritic cells;    macrophages;    IL‐;    15;    trans‐;    presentation;    CD70;   

DOI  :  10.1189/jlb.1209816

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThisstudytestedthehypothesisthatindividualmyeloidsubsetshaveadifferentialabilitytomaintainmemoryCD8TcellsviaIL‐15.AlthoughDCssupportIL‐15‐mediatedhomeostasisofmemoryCD8Tcellsinvivo,whethervariousDCsubsetsandothermyeloidcellssimilarlymediatehomeostasisisunknown.Therefore,westudiedtheabilityofdifferentmyeloidcellstomaintainmemoryCD8Tcellsinvitro.UsinganinvitrococoulturesystemthatrecapitulatedknownrolesofDCsandIL‐15onmemoryCD8Tcells,allinvitro‐derivedorexvivo‐isolatedDCsmaintainedCD8TcellsbetterthanrIL‐15alone,andFLT‐3L‐DCsarethemostefficientcomparedwithGM‐DCs,BM‐derivedmacrophages,orfreshlyisolatedDCs.AlthoughFLT‐3L‐DCsweretheleasteffectiveatinducingCD8Tcellproliferation,FLT‐3L‐DCspromotedbetterCD8TcellsurvivalandincreasedBcl‐2andMCL‐2expressioninCD8Tcells.TcellmaintenancecorrelatedonlypartiallywithDCexpressionofIL‐15RαandIL‐15,suggestingthatDCsprovidedadditionalsupportsignals.Indeed,intheabsenceofIL‐15signals,CD70/CD27furthersupportedCD8Tcellmaintenance.IFN‐αenhancedCD70expressionbyDCs,resultinginincreasedproliferationofCD8Tcells.Overall,thisstudysupportsourhypothesisbydemonstratingthatspecificDCsubtypeshadagreatercapacitytosupportmemoryCD8Tcellmaintenanceanddidsothroughdifferentmechanisms.Furthermore,thisstudyshowsthatIL‐15trans‐presentationcanworkinconjunctionwithothersignals,suchasCD70/CD27interactions,tomediateCD8Tcellhomeostasisefficiently...

【 授权许可】

CC BY