[Mechanisms of xenotransplant rejection]

The recent shortage of allogeneic human organs in transplantation medicine has led to a renewed interest in evaluating the feasibility of xenotransplantation, particularly of porcine origin. Discordant xenotransplants between phylogenetically distant species such as pig and primates are challenged by a series of strong rejection reactions. Hyperacute rejection is dominantly mediated by humoral responses of the immune system (natural antibodies, complement cascade) and the activation of coagulation factors, whereas delayed xenograft rejection and T-cell mediated responses are also mediated by elements of the cellular immune system. The mechanisms of chronic xenograft rejection remain to be elucidated. The present review is focused on the mechanisms of rejection and the immunobiology of discordant, vascularized xenotransplants. We attempt to provide a brief description of the dynamics, the humoral and cellular mediators, and the pathogenesis of xenograft rejection. Finally, an overview on potentially therapeutic strategies to overcome xenograft rejection is presented.