Human CD4+CD25+ regulatory T cells suppress anti-porcine xenogeneic responses

Due to the shortage of human organs, xenotransplantation is being explored as an alternative to allotransplantation, but immune rejection remains a major hurdle to its implementation. We tested the ability of human CD4(+)CD25(+) T cells (Treg cells) to suppress CD4(+) T cell-mediated anti-porcine xenoresponses usingin vitroassays. Human Treg cells were hyporesponsive to porcine cell stimulation and suppressed the proliferative response of CD4(+)CD25(-) T cells in a dose-dependent manner, and comparison of the allo- and xenoresponses indicated that more Treg cells might be required to suppress the xenogeneic response than the allogeneic response. Stimulation of CD4(+)CD25(-) T cells with porcine cells resulted in secretion of IFN-gamma, TNF-alpha, IL-10, IL-6 and IL-2, and Treg cells suppressed the secretion of these cytokines, as well as the CD4(+)CD25(-) T-cell cytolytic response against porcine cells. These results suggest a potential role for Treg cells in promoting xenograft survival.