Trogocytic CD137 transfer causes an internalization of CD137 ligand on murine APCs leading to reduced T cell costimulation

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

关键词: immune regulation;    IFN‐;    γ;   

DOI  :  10.1189/jlb.3A0213-079RRR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CD137ligand(CD137L)isexpressedonAPCsandcrosslinksCD137,apowerfulcostimulatorymoleculeonTcellsduringcognateinteractions,andtherebygreatlyenhancesimmuneresponses.WereportthatCD137canbetransferredfromactivatedTcellsandfromtumorcellsthatexpressCD137toothercellsviatrogocytosis.ThistrogocytictransferisindependentofCD137Lexpressionbytherecipientcell.However,ifCD137Lispresentontherecipientcell,thetransferredCD137bindstoCD137LandtheCD137‐CD137Lcomplexbecomesinternalized.TheremovalofCD137LfromthesurfaceofAPCslowerstheirabilitytocostimulateTcells,asevidencedbyareducedIFN‐γsecretion.RemovalofCD137LonAPCsbytrogocytictransferofCD137occurswithin1handrequirescell‐cellcontactandthecontinuouspresenceofCD137‐expressingcells.BidirectionalsignalingexistsfortheCD137receptor/ligandsystem,becauseCD137LalsosignalsintoAPCs.WeproposethatthetrogocytictransferofCD137fromactivatedTcellstoAPCsandthesubsequentremovalofCD137LfromAPCsisaphysiologicregulatorymechanismthatlimitsimmuneactivity.Furthermore,wehypothesizethatthetrogocytictransferofCD137occursincancersandquenchestheactivityofAPCs,contributingtothecancercellsescapingimmunesurveillance.Takentogether,ourfindingsdemonstratethatthetrogocytictransferofCD137leadstoaninternalizationofCD137LonAPCsandareductioninimmuneactivity...

【 授权许可】

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