HAMSTER BLOOD TRANSFUSION CAN INDUCE TOLERANCE TO CARDIAC XENOGRAFTS IN ABSENCE OF T-CELLS

Abstract

465 Introduction Donor-specific blood transfusion has been shown to prolong allograft survival. We investigated the effect of hamster blood transfusion (HBT) on cardiac xenograft survival in rats. Methods T-cell deficient, athymic Nude rats and immunocompetent Lewis rats served as recipients of hamster cardiac xenografts. Heparinized hamster blood, 1 ml, was injected i.v. at day -7 and day -3 prior to transplantation at day 0. Lewis rats were treated with Cyclosporin A (CSA) at 10 mg/kg/day, or 20 mg/kg/day, starting at day -4. Antibody titers (ABT) were measured by flow cytometry, as mean% of positive controls, using hamster thymocytes as target cells.Results See table.Second hamster cardiac xenografts were accepted indefinitely, when transplanted to long-term surviving nude rats, indicating tolerance. Conclusion Pre-transplant HBT can induce tolerance in athymic nude rats, but leads to hyper acute rejection in immunocompetent Lewis rats. Low dose CSA can prevent sensitization and hyperacute rejection after HBT, and combination of HBT with high dose CSA even leads to prolonged survival of hamster cardiac xenografts in Lewis rats. Timing of HBT is of critical importance and the tolerogenic effects are specific for HBT, since a first hamster heart induced hyperacute rejection of a second hamster cardiac xenograft. Further elucidation of the mechanisms involved in this model will offer insight into induction of xenotransplant hyporesponsiveness.