Long-term survival of rat cardiac allografts by intrathymic plus portal venous injections of donor bone marrow cells and short-term tacrolimus immunosuppression.

ABSTRACT

Intrathymic (IT) or portal venous (PV) injection of donor antigens has been shown to prolong organ acceptance in low responder rat strain combinations. We determined whether a combination of these strategies would prolong cardiac allograft survival in high responder combinations. Wistar Furth rats received 1 x 10(8) ACI rat bone marrow cells (BMCs) via IT, intravenous (IV), PV, IV + PV, IT + IV or IT + PV route at the time of ACI cardiac transplantation. Without tacrolimus (FK), all grafts were acutely rejected. With FK immunosuppression (1.5 mg/kg per day, I. M., days 0-4), single BMC injection did not increase graft survival beyond 93 days, whereas 70% of grafts survived indefinitely ( > 150 days) when IT and PV BMCs were combined. Animals receiving IT and PV BMCs also had less allograft vasculopathy. Thus, IT and PV injections of donor BMCs under a brief course of FK synergistically improve cardiac allograft survival.