Successful cardiac allografts in syngeneic radiation chimeras

Abstract

Successful cardiac allografts were accomplished across the major histocompatibility complex of rats. LEW and F344 (Ag-B2) rats were lethally irradiated and grafted with WF (Ag-B1) hearts on day 0. Either on day 0 or day 2, the hosts were repopulated with syngeneic hemopoietic cells. The best results were obtained (86%) when a mixture of 3.0 x10(7) non-adherent syngeneic bone marrow and thymus cells were used to repopulate the recipients. In contrast, all of the WF to LEW heart grafts were rejected within 30 days if syngeneic thoracic duct and bone marrow cells were used to repopulate the host. Tolerant rats bearing a functioning WF heart graft were able to mount a normal antibody response to SRBC and a proliferative response to Con A. They accepted a second WF heart or a WF kidney graft but rejected WF skin and bone marrow grafts as well as "third-party" ACl or BN hearts. The lymphocytes of tolerant rats had a reduced response to WF antigens as assayed by local or systemic graft-versus-host reactions in (LEW x WF)F1 recipients. Tolerance to the WF hearts was resistant to a large innoculum of normal spleen and lymph node cells. The unresponsive state could be transferred to unirradiated LEW rats with a mixture of spleen, thymus, lymph node and bone marrow cells.