Tolerance in xenotransplantation

Abstract

Purpose of review This review assesses recent progress in the induction of xenograft tolerance, with a focus on the strategies showing promise in preclinical large animal models. Recent findings True xenograft tolerance has been limited to rodent models. In large animal models, T cell costimulatory blockers have been widely used as a key component of immunosuppression in controlling xenograft rejection. Despite significant improvements in xenograft survival, blocking T cell costimulation has not yet shown the ability to achieve tolerance in primates. Development of an effective, nontoxic recipient conditioning regimen allowing donor marrow cell engraftment will be essential to the translation of the mixed chimerism approach to clinical xenotransplantation. Costimulatory blockade has been shown to promote this type of tolerance in rodent xenograft models. Thymic xenotransplantation with Gal-transferase knockout source pigs, for the first time, permitted porcine kidney xenograft survival in nonhuman primates for several months without rejection. Summary Tolerance induction is likely to be critical for clinical success of xenotransplantation. With further investigation, induction of xenotransplantation tolerance may be achieved in nonhuman primates and ultimately in humans.