Chinese researchers have shown taht altering or overexpressing the human programmed death ligand-1 (PD-L1) molecule in the endothelial cells of pig arteries reduces the conditions that lead to rejection. This strongly suggests that humans could receive altered porcine organs with fewer complications.
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 PIEChPD-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.
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