Promotion of incompatible allograft acceptance in rhesus monkeys given posttransplant antithymocyte globulin and donor bone marrow. I. In vivo parameters and immunohistologic evidence suggesting microchimerism

Abstract

This report extends previous studies demonstrating that prolonged acceptance of incompatible kidney allografts 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 immunosuppression. 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.