Syngeneic bone marrow expressing a single donor class I MHC molecule permits acceptance of a fully allogeneic cardiac allograft
Abstract
Bone marrow cells may be a useful vehicle for pretransplant delivery of alloantigen to induce tolerance in vivo. However, infusion of fully allogeneic bone marrow cells carries the risk of graft-versus-host disease. In order to reduce this risk while retaining the tolerogenic potential of the bone marrow infusion, we have investigated the ability of recipient bone marrow cells expressing a single donor MHC class I antigen to induce specific unresponsiveness in vivo. We show that 5x10(7) and 5x10(6) bone marrow cells from a transgenic strain of CBA mice, CBK, that express a single donor class I MHC gene, H2Kb (H2k + H2Kb), were able to induce long term survival of a fully allogeneic C57BL/10 (H2b) cardiac allograft in 80% and 20% of unmanipulated CBA (H2k) recipients, respectively, when administered intravenousely on the day of transplantation. In contrast, the same doses of fully allogeneic C57BL/10 donor bone marrow were completely ineffective at prolonging graft survival. When the interval between bone marrow infusion and transplantation was increased to 14 days, CBK bone marrow at either dose (5x10(6) and 5x10(7)) induced long term survival of C57BL/10 cardiac allografts in all recipients (MST>100 days) while fully allogenei...Continue Reading
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