Tolerance induction in a fully allogeneic combination using anti-T cell receptor-alpha beta monoclonal antibody, low dose irradiation, and donor bone marrow transfusion.

In a murine strain combination disparate in both H-2 antigens and minor histocompatibility antigens consisting of C57BL/6 (B6; H-2b, Mls-1b) mice as recipients and AKR/J (AKR; H-2k, Mls-1a) mice as donors, we reported that the administration of anti-TCR-alpha beta mAb nonspecifically suppresses the ability to reject allografts. However, such an effect was only temporary and all grafts were eventually rejected within 40 days in the anti-TCR-alpha beta mAb-treated mice. In this study, to induce donor-specific tolerance, the transfer of donor bone marrow cells was added to the administration of anti-TCR-alpha beta mAb but donor bone marrow cells were rejected and failed to cause donor-specific unresponsiveness. After donor bone marrow cell transfer in the anti-TCR-alpha beta mAb-treated mice, the B cells of the recipients were observed along with the production of antidonor antibody. To abolish the residual lymphocyte populations, low dose irradiation was also added. A long-lasting skin allograft tolerance can be achieved by the tolerance system, in which low dose irradiation was added to the combined treatment with anti-TCR-alpha beta mAb and transfer of donor bone marrow cells. Such a protocol also established central and peripheral chimerism, which suggests that hematopoietic chimerism is necessary to maintain the tolerance. B cells were completely abolished in recipients given this combined treatment and their antibody production against donor antigens after the transfer of donor bone marrow cells was also completely suppressed. A possible role of B cells in the rejection of donor bone marrow cells before the establishment of chimerism is discussed.