Skin allograft survival following intrathymic injection of donor bone marrow

Background. Success has been reported using intrathymic injection in the pr econditioning regimen to induce allograft tolerance. Although long-term sta ble tolerance has been achieved in numerous rodent vas cularized solid orga n allograft models, tolerance to skin transplants has only been achieved ac ross minor antigenic or concordant species disparities. This study sought t o induce tolerance across an allogeneic barrier in a rat model with a major genetic disparity. Materials and methods. Lewis rats were injected intrathymically with 1 x 10 (8) Brown-Norway (BN) bone marrow cells and intraperitoneally with 1.0 cc o f rabbit anti-rat anti-lymphocyte serum (ALS). Twenty-one days later, BN sk in grafts were placed on the injected animals. Control groups were included to isolate the effect of technique, thymic manipulation, strain specificit y, and ALS. Results. Animals receiving both intrathymic bone marrow cells and ALS had a skin graft median survival time of 24 days versus 8 days for the control g roup (P = 0.003). Groups receiving anti-lymphocyte serum alone or intrathym ic bone marrow cell injection alone exhibited no skin graft survival prolon gation. Mixed lymphocyte reactions revealed normal responsiveness of tolera nt animal lymphocytes to donor strain lymphocytes. Conclusions. This protocol utilizing the intrathymic injection of donor bon e marrow cells along with shortterm immunosuppression with anti-lymphocyte serum produced markedly prolonged survival of skin allografts transplanted across a major histocompatibility barrier. Although tolerance was incomplet e, significant prolongation has not previously been reported in genetic dis parities of this degree. These results suggest that the application of this technique for central immune modulation may be beneficial for allograft to lerance induction and deserves further study in large animals models. a lee s Academic Press.