Induction of mixed lymphocyte reaction nonresponsiveness after chimeric thymus transplantation

Discussion still continues regarding whether self-tolerance is imparted within the thymus by the thymic epithelial cells (TEC) or by the bone marrow-derived (BMD) dendritic cells and macrophages. Many experiments suggest that BMD cells may be the major cells responsible for inducing tolerance within the thymus. In order to address this question and to see whether thymus chimerism could play a role in establishing transplantation tolerance, we looked in the present experiments at the induction of in vitro tolerance after transplantation of chimeric thymuses. Chimeric thymuses were constructed by injecting T-depleted C3H (H2k) bone marrow into lethally irradiated BALB/c (H2d) mice and were thus composed of TEC of BALB/c and BMD cells of C3H origin, something which was verified with immunoperoxidase staining. Subsequently, chimeric thymuses were transplanted into thymectomized BALB/c mice that were lethally irradiated and reconstituted with T-depleted syngeneic BALB/c bone marrow. In 8 out of 11 BALB/c mice this procedure was successful, and in all chimeric thymus graft-bearing mice, specific tolerance for C3H (H2k) antigens was documented in the mixed lymphocyte reaction (MLR). These experiments thus show that: (1) immunological tolerance can be imparted by BMD cells in the thymus and (2) the presence of chimerism within the thymus could be one of the mechanisms involved in the establishment or maintenance of transplantation tolerance.