Hamster cardiac xenografts are protected against antibody mediated damage,early after transplantation to Lewis rats

Antibodies play a crucial role in the rejection of xenografts. We tested th e hypothesis that xenografts are protected against antibody-mediated attack early after transplantation in a concordant model. We investigated the rol e of xenoreactive antibodies as a stimulus for protection and the effects o f a total blockade of the antibody response by the leflunomide analog malon onitrilamide 279. Hamster cardiac xenografts were transplanted to Lewis rat recipients. Second transplants and retransplants of xenografts were perfor med to untreated rats that had a xenograft in place for 3 d. Untreated rats rejected hamster cardiac xenografts after 4.0 +/- 0.0 d. Significant level s of anti-donor IgM, as measured by flowcytometry, were present on day 3 af ter transplantation (11.2% +/- 2.8 vs. 1.2% +/- 0.0 on day 0, P <0.001). 'F resh' second xenografts transplanted to rats that had a first xenograft in place for 3 d and had anti-hamster antibodies, underwent hyperacute rejecti on. The first xenografts remained functioning. Xenografts that were removed on day 3 from untreated rats and then retransplanted remained functioning. Xenografts that were removed on d 3 from rats that had been treated with m alononitrilamide 279, 15 mg/kg/d and were retransplanted underwent hyperacu te rejection. IgM levels at the time of removal were 1.1% +/- 0.5 in these rats and not different from baseline (P=0.96). We conclude that xenografts are protected against antibody-mediated damage early after transplantation. The presence of anti-donor antibodies might be an essential stimulus for t he induction of protection. There seems to be a delicate balance between th e injurious and protective effects of antibodies. Treatment strategies that are designed to block antibody formation completely might prevent the indu ction of protection.