Pretransplant conditioning with donor-specific transfusions using heated blood and cyclosporine. Preservation of the transfusion effect in the absence of sensitization.

Abstract

Previous studies from our laboratory showed that pretransplant conditioning with fresh donor-specific blood (DST) combined with cyclosporine (CsA) resulted in long-term prolongation of ACI heterotopic cardiac allografts in LEW recipients treated with subtherapeutic doses of CsA. The concomitant administration of CsA profoundly reduced but did not eliminate the DST-induced sensitization. The purpose of the present study was to investigate in the ACI-to-LEW cardiac allograft model whether heat-treatment of the blood would further reduce the sensitizing potential of DST while maintaining their benefits in our protocol. Fresh heparinized ACI blood was heated at 45 degrees C for 60 min. Then 1.5 ml was administered i.v. to LEW rats on day -8 with respect to grafting (day 0). Controls received heat-treated BUF blood. Donor heat-treated blood (HT-DST), unlike fresh blood, did not induce a humoral cytotoxic response and resulted in the prolongation of cardiac allograft survival (13.2 +/- 2.7 vs. 7.2 +/- 1.0; P less than 0.01). Treatment of HT-DST recipients with postoperative subtherapeutic doses of CsA (2.5 mg/kg/day x 30) extended graft survival (46.6 +/- 22.0 vs. 7.7 +/- 2.0 days; P less than 0.01). The combined pretransplant administration of HT-DST and CsA followed by posttransplant subtherapeutic doses of CsA led to long-term prolongation of cardiac grafts (122.0 +/- 73.0 vs. 31.7 +/- 22.0 days; P less than 0.01). These studies demonstrate that heat-treatment of allogeneic blood eliminates the humoral responses to DST and actually enhances their beneficial effects in terms of graft survival. Such effects can be dramatically increased by CsA. The possible mechanism of these phenomena are discussed.