Development of tolerance to donor type and host type H-2 antigens following transplantation of allogeneic bone marrow in mice

The responsiveness in mixed lymphocyte culture (MLC) against donor, host or third party antigens both in the thymus and in the spleen was studied in allogeneic chimeras at different time intervals post-bone marrow transplantation (BMT), and the results were correlated with the development of host and donor-type cells in the thymus. Three significant findings were revealed by this analysis. (1) Low but significant anti-host responses are present in allogeneic chimeras despite the lack of graft-versus-host disease. The anti-host responses in MLC can initially be detected in the thymus during the first 3 weeks post-transplant. A significant anti-host response can subsequently be detected in the spleen during the second month post-BMT. (2) The MLC anti-host responses are always higher than the anti-donor responses, indicating that new bone marrow-derived cells which arrive in the thymus after BMT may have a more important role in tolerance induction than the thymus epithelium, which is of host origin and cannot be involved in clonal deletion of donor anti-donor responses. (3) A substantial number of residual host-type prothymocytes survives 9.0 Gy total body irradiation, as manifested by their progeny in the thymus, and reaches a maximum number of 26.6 x 10⁶ cells on day 15 post-BMT, before being gradually replaced in the thymus by donor-type thymocytes. The host-type thymocytes are tolerant in MLC towards donor-type cells. It is speculated that such host-type cells could cooperate with host-type antigen-presenting cells more effectively than donor-type cells, and could therefore play an important role in maintaining immune functions during the initial and critical post-transplant period.