Organ-specific unresponsiveness induced by intrathymic injection of donor bone marrow cells and a short course of immunosuppression in the rat heart transplantation model.

Donor- and organ-specific unresponsiveness to Brown Norway (BN) heart allografts was achieved in Lewis (LEW) rats by giving intrathymic donor bone marrow cells (ITBMC) and immunosuppression at the time of transplantation. Antilymphocyte serum (ALS) (1 ml, days 0, 2, 4) extended graft survival to a median survival time (MST) of 29.5 days (n = 6), while ALS + ITBMC extended survival to over 120 days (n = 6). FK506 (1 mg/kg, days 0, 2, 4, 6, 8) too prolonged survival in the FK + ITBMC (n = 6; MST > 140 days) and FK (n = 5; MST > 140 days) groups. BN skin grafting provoked the rejection of long-surviving BN heart grafts in the FK group (n = 5; MST = 14 days), but did not do so in either the ALS + ITBMC (n = 2; MST > 100 days) or the FK + ITBMC (n = 4; MST > 93 days) groups. In the FK + ITBMC group, two of the rats which rejected BN skin grafts received a second BN heart, resulting in the graft being accepted indefinitely (> 100 days) without causing the rejection of the first BN heart grafts. These facts suggest that ITBMC and concurrent T cell depletion are decisive for induction of unresponsiveness by this protocol. BN and WF (Wistar Furth) skin grafts were eventually rejected in the LEW rats which accepted BN heart grafts. Persistent allogeneic chimerism was demonstrated in the graft and recipient spleen, suggesting that chimerism may be one of the possible mechanisms of unresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)