title: Human PD-L1-overexpressing porcine vascular endothelial cells induce functionally suppressive human CD4+CD25hiFoxp3+ Treg cells.
abstract: In xenotransplantation models, direct activation of hCD4(+) T cells by porcine VECs leads to a robust proliferation of T cells. To investigate the underlying mechanisms, human antiporcine MLEC culture was used to investigate cross-species cell interactions, proliferation of hCD4(+) T cells, and induction of human cytokines. We report that xenoantigen presentation by PIEC expands hCD4(+) Foxp3(+) Tregs and hCD4(+) Foxp3(-) Teffs, and this process is dependent on porcine MHC-II antigen expression. Stable transfection of hPD-L1 into PIEC inhibits Teff proliferation, but Treg proliferation is not affected. Surprisingly, IL-10 production by hCD4(+) T cells is augmented significantly by PIEC(hPD-L1). Notably, hPD-L1-induced Tregs have higher suppressive potency and mediate suppressive function partially through IL-10 and CD73. This study opens the possibility of using hPD-L1-overexpressing porcine VECs as a novel therapeutic to allow tolerance of xenotransplants and also supports the possibility of using hPD-L1 transgenic pigs as xenotransplant donors.
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai, China. qingding69@gmail.com
authors.forename: Qing
authors.initials: Q
authors.lastname: Ding
authors.forename: Liming
authors.initials: L
authors.lastname: Lu
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Zhou
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Kuang-Yen
authors.initials: KY
authors.lastname: Chou
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D060890:B7-H1 Antigen; D015704:CD4 Antigens / Q000276:immunology; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000276:immunology*; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D013556:Swine, Miniature; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014162:Transfection; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit