Induction of donor-specific tolerance to allogeneic hepatocytes by allogeneic bone marrow transplantation.

Allogenic hepatocytes are rejected within a few days after transplantation without immunosuppression. We previously showed that the peripheral tolerance did not effectively prolong the survival of allogeneic hepatocytes transplanted in the spleen, because anergic T cells lysed allogeneic hepatocytes through Fas/Fas ligand system. The aim of this study was to address whether or not the central tolerance induced by allogeneic bone marrow transplantation (BMT) allows transplanted hepatocytes to survive in the spleen of the recipient. Bone marrow cells obtained from C57BL/6 (B6) donor mice were injected intravenously into lethally irradiated BALB/c recipients. Ninety percent of the recipient mice were able to survive more than 30 days, although all of the non-BMT controls died within 12 days. Full donor chimerism was observed in the recipient. Then hepatocytes from B6 mice were transplanted into the spleen of BALB/c mice at 30 days post-BMT. The transplanted donor-hepatocytes were able to survive for over 7 days, while those from third-party mice (C3H/He) were rejected within a few days. These findings demonstrate that donor-specific tolerance was induced by allogeneic BMT. Furthermore, the induction of central tolerance, but not peripheral tolerance, may be a useful strategy for prolonging the survival of allogeneic hepatocytes in the spleen.