PROMOTION OF INCOMPATIBLE ALLOGRAFT ACCEPTANCE IN RHESUS MONKEYS GIVEN POSTTRANSPLANT ANTITHYMOCYTE GLOBULIN AND DONOR BONE MARROW

Abstract

This report extends previous studies demonstrating that prolonged acceptance of incompatible kidney allo-grafts in rhesus monkeys can be achieved by a short recipient rabbit antithymocyte globulin (RATG) treatment course followed by donor bone marrow infusion on day 12 without a requirement for chronic immune-suppression. Serial studies of antilymphocyte cyctotoxic antibody in recipients' sera following RATG injections showed pan-lymphocyte-reactive antibody present until day 10 posttransplant. On days 11 and 12, pan-lymphocyte-reactive antibody was no longer detectable, but cytotoxic antibody specific for mature T cells remained in recipients' sera. These findings might explain the critical time relationship between antithymocyte globulin treatment and donor bone marrow infusion, and further suggest that the tolerance-promoting cell in donor bone marrow is not a mature T cell, but rather a pre-T or a non-T cell. Finally, it was found that this treatment protocol resulted in development of lymphoid nodules in the transplanted kidney that express a CD8-positive, FcIgG-receptor-positive phenotype and appear to be of donor origin. The possibility of a veto cell type of mechanism is discussed as an explanation for the promotion of allograft acceptance in this model.