Biphasic activity of CD137 ligand‐stimulated monocytes on T cell apoptosis and proliferation

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

关键词: cell death;    reactive oxygen species;   

DOI  :  10.1189/jlb.1010569

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CD137L(4‐1BBL)isamemberoftheTNFSFandisexpressedonAPCsasatransmembraneprotein.ReversesignalingbyCD137LinmonocytescausescellactivationanddifferentiationtomatureinflammatoryDCsthatcanstimulateTcellproliferation.However,CD137LagonistshavealsobeenreportedtoinduceapoptosisinPBMCs.Thisstudyaimedatclarifyingtheseseeminglyopposingactivities.WefindthatthedyingcellswithinPBMCsareTcellsandthatthisTcelldeathisdependentonmonocytesandcorrelateswiththemonocyte:Tcellratio.ThisCD137L‐induced,monocyte‐mediatedTcellapoptosisisreminiscentofMDCD,andbotharecellcontact‐dependent.TcelldeathisnotmediatedbyCD95orDR4or‐5butbyROSproducedbytheTcells.Tcellapoptosisisrestrictedtothefirst24hofstimulation,andatlatertime‐points,themonocytesdifferentiatetoinflammatoryDCsundertheinfluenceofCD137LsignalingandacquirethecapacitytostimulateTcellproliferationfromDay4onward.Thisbiphasicactivitymaycontributetoinfection‐inducedTcellattrition,whereintheearlyphase(<24h)ofaninfection,massiveTcellapoptosisoccursbeforetheantigen‐specificTcellsexpand...

【 授权许可】

CC BY