Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Human PD‐L1‐overexpressing porcine vascular endothelial cells induce functionally suppressive human CD4+CD25hiFoxp3+ Treg cells | |
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】
CC BY
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