Prolonged limb allograft survival with CD40 costimulation blockade, T-cell depletion, and megadose donor bone-marrow transfusion

The purpose of this study was to determine the efficacy of a treatment regimen consisting of CD40 costimulation blockade, T-cell depletion, and megadose donor bone marrow transfusion in the limb allograft model. C57BI/6 mice underwent limb transplantation from Balb/c mice and received MR1 (anti-CD40 ligand monoclonal antibody), and CD4⁺ and CD8⁺ T cell-depleting antibodies with and without 120 × 10⁶ donor bone-marrow transfusion. Recipients treated only with antibodies showed rejection at 51.4 ± 17 (mean ± SEM) days, while those who also received donor bone marrow had allograft survival of 67 ± 16.4 days, with a range up to 91 days. Treated specimens with rejection had less lymphocytic infiltration than untreated controls. Recipients of donor bone marrow also demonstrated early mixed chimerism, which disappeared after 1 month. While allograft survival was prolonged, tolerance was not achieved, and the mechanism of rejection was more consistent with a chronic process.