Acceptance of cardiac allografts by lethally irradiated rats repopulated with syngeneic bone marrow. Role of class I and class II alloantigens

Abstract

LEW rats (RT1l) that are lethally irradiated and repopulated with syngenic bone marrow accept WF (RT1u) cardiac allografts. If bone marrow repopulation is delayed for two days after irradiation and operation, grafts containing passenger leukocytes (nonperfused grafts) are generally rejected, but perfused grafts, which have fewer passenger leukocytes, are accepted. If bone marrow is given on the same day as irradiation and surgery, then both perfused and nonperfused grafts are accepted. The difference in acceptance of grafts by recipients that are repopulated on day 0 as opposed to day 2 depends on class II alloantigens, because grafts that are similar to LEW for class II antigens are not rejected by day-2-repopulated recipients. Also, the acceptance of totally major histocompatibility complex (MHC)-mismatched cardiac allografts by day-0-repopulated recipients is influenced by a radiation-resistant host cell. Splenectomy of the irradiated and repopulated recipient prevents tolerance induction unless syngeneic irradiated spleen cells are returned to the recipient. Thus class II alloantigen disparities appear to be a major barrier to tolerance induction in the system of total body irradiation and syngeneic bone marrow reconstitution, although proper timing of bone marrow administration can minimize rejection of completely MHC-mismatched grafts.