EFFICACY OF COMBINING DONOR-SPECIFIC PRESENSITIZATION WITH A SIMULTANEOUS SINGLE INJECTION OF TACROLIMUS ON PULMONARY ALLOGRAFTS

Background: We investigated the effects of combining donor-specific pr esensitization with a simultaneous injection of tacrolimus by use of a fully allogeneic rat lung allograft model. Methods: Lungs from Brown Norway donor rats were orthotopically transplanted into Lewis recipien t rats. Seven days before transplantation, allograft recipients receiv ed a transfusion of donor splenocytes (1 x 10(8) cells, intravenously) , tacrolimus (3 or 1.5 mg/ kg, intramuscularly), or a combination. No posttransplantation immunosuppression was given. In the transplantatio n study, graft survival was evaluated, and histologic characteristics of acute rejection were graded. In the in vitro studies, mixed lymphoc yte reaction assays were used to investigate the effects of pretreatme nt on immune response. Results: The graft survival evaluation disclose d that untreated rats rejected the allografts at 4.6 +/- 0.2 days. Don or splenocyte transfusion alone accelerated the graft rejection (3.3 /- 0.2 days). Tacrolimus (3 mg/kg) alone moderately improved the graft survival (8.7 +/- 0.6 days). When donor splenocyte transfusion was co mbined with tacrolimus, graft survival was significantly increased to 29.6 +/- 12.0 days. In a mixed lymphocyte reaction assay, peripheral b lood lymphocytes obtained from animals pretreated with donor splenocyt e transfusion alone seemed to be hyperresponsive against the donor lym phocytes. In contrast, donor splenocyte transfusion with tacrolimus si gnificantly suppressed the proliferative response against the donor ly mphocytes but not against third-party lymphocytes obtained from naive Wistar King A rats. Conclusion: These data demonstrate that donor-spec ific presensitization with a simultaneous single injection of tacrolim us prevented both sensitization and graft rejection and induced donor- specific unresponsiveness. J Heart Lung Transplant 1997.