Pathogenesis of and potential therapies for delayed xenograft rejection

Abstract

For several decades, it has been known that host anti-graft antibodies and complement lead to hyperacute rejection. When interest in xenotransplantation reemerged a decade ago, the expectation of most was that if hyperacute rejection could be overcome, the only remaining problem would be the xenograft equivalent of T-cell–mediated rejection of allografts. Unfortunately, this did not happen. Rather, another “phase” of xenograft rejection, termed delayed xenograft rejection, occurred. We discuss delayed xenograft rejection in this article, both with regard to mechanisms that lead to its manifestations and possible therapeutic strategies that might be used to overcome it. Major emphasis is given to the central and important role played by elicited anti-graft antibodies in the initiation of delayed xenograft rejection and to possible reasons for achieving accommodation, the survival of the graft in the presence of anti-graft antibodies, and complement.