期刊论文详细信息
Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society
GM‐CSF‐induced, bone‐marrow‐derived dendritic cells can expand natural Tregs and induce adaptive Tregs by different mechanisms
关键词: T cells;    autoimmunity;    Foxp3;    OX40‐;    OX40L;    TGF‐;    β;   
DOI  :  10.1189/jlb.0310154
学科分类:生理学
来源: Federation of American Societies for Experimental Biology
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【 摘 要 】

Inourearlierwork,wehadshownthatGM‐CSFtreatmentofCBA/JmicecansuppressongoingthyroiditisbyinducingtolerogenicCD8α−DCs,whichhelpedexpandand/orinduceCD4+Foxp3+Tregs.ToidentifytheprimarycelltypethatwasaffectedbytheGM‐CSFtreatmentandunderstandthemechanismbywhichTregswereinduced,wecomparedtheeffectofGM‐CSFonmaturedspDCsandBMDCprecursorsinvitro.MaturedspDCsexposedtoGM‐CSFexvivoinducedonlyamodestincreaseinthepercentageofFoxp3‐expressingTcellsincocultures.Incontrast,BMcells,whenculturedinthepresenceofGM‐CSF,gaverisetoapopulationofCD11c+CD11bHiCD8α−DCs(BMDCs),whichwereabletoexpandFoxp3+TregsuponcoculturewithCD4+Tcells.Thiscontact‐dependentexpansionoccurredintheabsenceofTCRstimulationandwasabrogatedbyOX40Lblockage.Additionally,theBMDCssecretedhighlevelsofTGF‐β,whichwasrequiredandsufficientforadaptivedifferentiationofTcellstoFoxp3+Tregs,onlyuponTCRstimulation.TheseresultsstronglysuggestthattheBMDCsdifferentiatedbyGM‐CSFcanexpandnTregsandinduceadaptiveTregsthroughdifferentmechanisms...

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