Downregulation of cytolytic activity of human effector cells by transgenic expression of human PD-ligand-1 on porcine target cells.

Cellular rejection is a relevant hurdle for successful pig-to-primate xenotransplantation. We have shown previously that the induction of a human anti-pig T cell response (in vitro activation of CD4(+) T cells) can be suppressed by the overexpression of human negative costimulatory ligands (e.g.

Stimulatory and inhibitory receptor interactions in xenotransplantation.

Purpose Of Review: Cellular human antipig immune responses are increasingly recognized as an important barrier to successful clinical xenotransplantation. This review addresses the role of monocytes/macrophages, natural killer (NK) cells, and T cells in xenograft rejection. We focus on the receptor-ligand interactions that regulate the responses of these cells to porcine tissues and thus could be targets for immunomodulation.

Suppression of human T-cell activation and expansion of regulatory T cells by pig cells overexpressing PD-ligands.

Background: Genetic modification of pigs (e.g., transgenic expression of human complement regulatory molecules or inactivation of alpha1,3galactosyltransferase) enabled the development of promising strategies to overcome hyperacute rejection after pig-to-primate xenotransplantation.