Methods: C57Bl/6 mice were recipients of Balb/c limb allografts. Experimental groups are as follows: Group 1 – untreated allograft; Group 2 – treatment with MR1, CD4/8 TCD; Group 3 – MR1, CD4/8 TCD, high-dose BMT; Group 4 – MR1, CD4 TCD, high-dose BMT. High-dose BMT consists of 120 million unseparated bone marrow cells given IP on postoperative day 3. MR1 and TCD antibodies are administered at 500 mcg IP on days 0, 2, 4 and 6. Additional groups will be studied based on the findings of these initial groups. Histology and immunohistochemistry will be performed on all specimens. Chimerism will be evaluated in recipients with long-term allograft survival by real-time PCR.

Results (work in progress): Untreated recipients (Group 1) rejected their limb allografts after a mean of 9 days. Recipients treated with MR1 and complete T cell depletion only (Group 2) demonstrate allograft survival to 1 month at this time. Transplant recipients treated with MR1, complete T cell depletion, and high-dose BMT (Group 3) also demonstrate limb allograft survival up to 6 weeks presently. These groups will continue to be monitored until signs of rejection are noted.

Conclusion: Brief antibody-based induction regimens are demonstrating promise for the induction of immune unresponsiveness in the limb allograft model. Because a whole limb allograft includes vascularized bone marrow, components such as TBI and BMT that are required for the survival of organ and non-vascularized skin allografts may not be necessary in limb transplantation. Because anti-CD40L antibody controls the CD4 T cell response but is less effective against CD8 T cells, partial rather than complete TCD when combined with costimulation blockade may be sufficient for allograft survival.