Human PD‐L1‐overexpressing porcine vascular endothelial cells induce functionally suppressive human CD4+CD25hiFoxp3+ Treg cells

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

关键词: xenotransplantation;    PD‐;    1;    negative costimulation;    regulatory T cells;    IL‐;    10;    CD73 (ecto‐;    5′;    ‐;    nucleotidase);   

DOI  :  10.1189/jlb.1210691

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inxenotransplantationmodels,directactivationofhCD4+TcellsbyporcineVECsleadstoarobustproliferationofTcells.Toinvestigatetheunderlyingmechanisms,humanantiporcineMLECculturewasusedtoinvestigatecross‐speciescellinteractions,proliferationofhCD4+Tcells,andinductionofhumancytokines.WereportthatxenoantigenpresentationbyPIECexpandshCD4+Foxp3+TregsandhCD4+Foxp3–Teffs,andthisprocessisdependentonporcineMHC‐IIantigenexpression.StabletransfectionofhPD‐L1intoPIECinhibitsTeffproliferation,butTregproliferationisnotaffected.Surprisingly,IL‐10productionbyhCD4+TcellsisaugmentedsignificantlybyPIEChPD‐L1.Notably,hPD‐L1‐inducedTregshavehighersuppressivepotencyandmediatesuppressivefunctionpartiallythroughIL‐10andCD73.ThisstudyopensthepossibilityofusinghPD‐L1‐overexpressingporcineVECsasanoveltherapeutictoallowtoleranceofxenotransplantsandalsosupportsthepossibilityofusinghPD‐L1transgenicpigsasxenotransplantdonors...

【 授权许可】

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