Downregulation of Swine Leukocyte Antigen Expression Decreases the Strength of Xenogeneic Immune Responses towards Renal Proximal Tubular Epithelial Cells

Xenotransplantation reemerged as a promising alternative to conventional transplantation enlarging the available organ pool. However, success of xenotransplantation depends on design and selection specific genetic modifications development robust assays allowing for precise assessment tissue-specific immune responses. Nevertheless, cell-based are often compromised by low proliferative capacity primary cells. Proximal tubular epithelial cells (PTECs) play crucial role in kidney function. Here, we generated immortalized PTECs (imPTECs) overexpression simian virus 40 T large antigen. ImPTECs not only showed typical morphology phenotype, but, contrast PTECs, they maintained steady cell cycling rates functionality. Furthermore, swine leukocyte antigen (SLA) class I II transcript levels were reduced up 85% after transduction with lentiviral vectors encoding short hairpin RNAs targeting β2-microglobulin transactivator. This contributed reducing xenogeneic T-cell cytotoxicity (p < 0.01) decreasing secretion pro-inflammatory cytokines such IL-6 IFN-γ. study feasibility generating highly immunomonitoring assays. Silencing SLA expression was demonstrated be an effective strategy prevent cellular responses may strongly support graft survival xenotransplantation.