Pre‐transplant blood transfusion and cyclosporin A induce long‐term hamster cardiac xenograft survival in immunocompetent rats

Abstract

In previous studies we have shown that pre-transplant hamster blood transfusion (HBT) can induce non-responsiveness in the T cell independent immunecompartment and result in tolerance towards hamster cardiac xenografts (Xgs) in T cell deficient athymic nude rats. In this study we test the combination of pre-transplant HBT with cyclosporin A (CSA) in immunocompetent Lewis rats. Before transplantation of a hamster cardiac Xg, 1 ml hamster blood was administered to nude rats or Lewis rats. CSA dissolved in olive oil was given orally at varying doses. Anti-hamster antibodies were measured by flowcytometry. In nude rats HBT 3 days before transplantation resulted in 100% long-term survival >100 days (n=9). In Lewis rats, HBT resulted in hyperacute rejection (HAR) (n=6). Treatment of nude rats with CSA at doses varying from five to 20 mg/kg/day and treatment of Lewis rats with CSA five or 10 mg/kg/day did not effect Xg survival. However, treatment of Lewis rats with CSA 20 mg/kg/day led to long-term survival of five of nine Xgs (p <0.01). Combination of HBT with CSA 10 mg/kg/day in Lewis rats resulted in long-term survival of four of seven Xgs. HBT and CSA 20 mg/kg/day resulted in 100% long-term survival (n=9). Immunoglobulin M (IgM) increased after HBT and CSA in these Lewis rats, but decreased after transplantation and remained low over time. When CSA was discontinued, IgM increased and Xgs were rejected (n=3). This study confirms that pre-transplant HBT results in long-term survival of hamster cardiac Xgs in nude rats. HBT and CSA have strong synergistic effects in immunocompetent Lewis rats. Combination of HBT with CSA treatment leads to long-term Xg survival in Lewis rats, whereas HBT alone results in HAR. The presence of T cells has a dominant influence on Xg survival after pre-transplant blood transfusion.