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- W4313373085 abstract "Abstract Background Xenotransplantation using genetically-engineered (GE) pig organs offers an unlimited supply of organs for patients with end-stage organ failure. Disrupting the porcine GGTA1/CMAH/β4GalNT2 genes (TKO) markedly reduces binding of human natural anti-pig antibodies in human to carbohydrate antigens expressed on the pig organ. However, more evident have demonstrated that T cell responses play a major role in xenogeneic rejection, and that immunosuppression alone is likely incapable of completely suppressing these responses. The object of this study is at an organ-specific level to evaluate human T cell-mediated response against GE pig renal microvascular endothelial cells (RMEC) with or without swine leukocyte antigen (SLA) class I or II. Methods Primary RMEC were isolated from the GGTA1/CMAH knockout (DKO) pigs, and immortalized using Lenti-SV40 T. The gene editing was performed to create specific TKO RMEC cell lines expressing SLA class II. Stimulation of human T cell activation or proliferation by RMEC was performed flow cytometry-based mixed lymphocyte reaction (MLR). Results The specific GE cells lacking carbohydrates or expressing SLA class I or II were confirmed. MLR data shows that human CD4+ T cell proliferation by CD31+ RMEC was higher than that by fibroblast-like renal cells (RC), and was significantly inhibited by immunosuppressive drugs. Furthermore, both of CD69+ and CD25+ T cells were significantly enhanced by RMEC with expression of SLA class I and II compared with SLA class I alone. Conclusion Porcine RMEC express SLA class I/II and known costimulatory molecules and have the ability to simulate human T cell proliferation. RMEC will be a useful reagent for the further study of xenotransplantation." @default.
- W4313373085 created "2023-01-06" @default.
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- W4313373085 date "2020-05-01" @default.
- W4313373085 modified "2023-09-25" @default.
- W4313373085 title "The effect of SLA expression on genetically-engineered pig renal cells on the human T cell xenoresponse" @default.
- W4313373085 doi "https://doi.org/10.4049/jimmunol.204.supp.161.29" @default.
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