Human regulatory T cells control TCR signaling and susceptibility to suppression in CD4+ T cells

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

关键词: Treg;    Teff proliferation;    cell surface markers;   

DOI  :  10.1189/jlb.2HI0815-334R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

HumanCD4+CD25hiFOXP3+regulatoryTcellsmaintainimmunologictoleranceandpreventautoimmuneandinflammatoryimmuneresponses.RegulatoryTcellsundergoasimilaractivationcycleasconventionalCD4+Tcellsuponantigenstimulation.Here,wedemonstratethatTcellreceptorsandcostimulationarerequiredtoactivatetheregulatoryTcellsuppressivefunction.RegulatoryTcellssuppressedtheTcellreceptorsignalingineffectorTcellsinatime‐dependentmannerthatcorrespondedwithinhibitionofcytokineproductionandproliferation.ModulationoftheactivationlevelandtherebythesuppressivecapacityofregulatoryTcellsimposeddistinctTcellreceptorsignalingsignaturesandhyporesponsivenessinsuppressedandproliferatingeffectorTcellsandestablishedathresholdforeffectorTcellproliferation.TheimmunesuppressionofeffectorTcellswascompletelyreversibleuponremovalofregulatoryTcells.However,thestrengthofpriorimmunesuppressionbyregulatoryTcellsandcorrespondingTcellreceptorsignalingineffectorTcellsdeterminedthesusceptibilitytosuppressionuponlaterreexposuretoregulatoryTcells.ThesefindingsdemonstratehowthestrengthoftheregulatoryTcellsuppressivefunctiondeterminesintracellularsignaling,immuneresponsiveness,andthelatersusceptibilityofeffectorTcellstoimmunesuppressionandcontributetounveilingthecomplexinteractionsbetweenregulatoryTcellsandeffectorTcells...

【 授权许可】

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