K12/SECTM1, an interferon‐γ regulated molecule, synergizes with CD28 to costimulate human T cell proliferation

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

关键词: chromatin immunoprecipitation;    graft‐;    versus‐;    host disease;    β;    ‐;    galactosidase;   

DOI  :  10.1189/jlb.1011498

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CD7isacell‐surfacemolecule,expressedonTlymphocytesandNKcells,whichfunctionsasacostimulatoryreceptorforTcellproliferation.SECTM1hasbeenproposedasaligandforCD7.However,theexpressionpatternofthismoleculeinhumanimmunecellsandroleinhumanTcellfunctionremainunclear.Inthepresentstudy,usinghumanrSECTM1,wedemonstratethatSECTM1stronglycostimulatesCD4andCD8TcellproliferationandinducesIFN‐γproduction,likelyviaaCD7‐dependentmechanism.Inaddition,SECTM1synergizeswithsuboptimalanti‐CD28tostronglyaugmentTcellfunctions.WefoundarobustinductionofIL‐2productionwhenSECTM1andanti‐CD28signalswerepresentwithTCRligation.Furthermore,additionofSECTM1intoaMLRsignificantlyenhancedproliferationofalloantigen‐activatedTcells,whereasblockadeofSECTM1inhibitedTcellproliferationinatwo‐wayMLRassay.SimultaneouslyblockingtheeffectofSECTM1,alongwithCTLA‐4/Fc,diminishestwo‐wayMLR.Finally,wedemonstratedthatexpressionofSECTM1isnotdetectedinmonocytesandimMoDCsattheproteinlevel.However,itisstronglyinducedbyIFN‐γinmonocytesandimMoDCs,andthisinductionisSTAT1‐dependent.TheseresultsindicatethatSECTM1isabroadlyexpressed,IFN‐γ‐induciblemolecule,whichfunctionsasapotentcostimulatoryligandforTcellactivationandissynergisticwithanti‐CD28...

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