Induction of xenotransplant tolerance

Clinical xenotransplantation will depend on the induction of xeno-tolerance. Conversely, xenotransplantation may offer opportunities to induce transplantation tolerance. We have previously shown that, xenotransplant tolerance for vascularized hamster organs could be achieved in athymic rats as far as the T-cell independent xeno-reactivity is concerned. This tolerance was shown to be based on specific T-independent B lymphocyte and NK cell unresponsiveness. In the present study we have shown that this T-independent xeno-tolerance can be achieved also in a semi-discordant situation using rat recipients with high titers of pre-existing anti-hamster IgM xenoantibodies. In addition, we showed that T-independent xeno-tolerance can also be induced together with T-dependent xeno-tolerance using xeno-thymus transplantation. These experiments may be of relevance for clinical xenotransplantation. The major next question to be addressed is to see how self tolerance in xeno-thymus grafted recipients can be improved as until now the latter recipients usually develop a multi-organ autoimmune syndrome, several weeks after transplanting a xeno-thymus.