PROLONGED SURVIVAL OF RAT ISLET AND SKIN XENOGRAFTS IN MICE TREATED WITH DONOR SPLENOCYTES AND ANTI-CD154 MONOCLONAL-ANTIBODY

Treatment of C57BL/6 mice with one transfusion of BALB/c spleen cells and a brief course of anti-CD154 (anti-CD40 ligand) antibody permits B ALB/c islet grafts to survive indefinitely and BALB/c skin grafts to s urvive for similar to 50 days without further intervention. We now rep ort adaptation of this protocol to the transplantation of islet and sk in xenografts. We observed prolonged survival of rat islet xenografts in mice treated with donor-specific spleen cell transfusion and anti-C D154 monoclonal antibody (mAb). Challenge islet xenografts placed on t hese animals indicated that graft acceptance was species-specific but not strain specific. Spleen cells from recipients bearing intact graft s led to rejection of rat islet xenografts in scid mice, suggesting th at graft acceptance was not due to complete clonal deletion of xenorea ctive cells. We also observed prolonged survival of rat skin xenograft s in mice treated with donor-specific transfusion and antiCD154 mAb. P rolonged survival of skin xenografts was also species specific. We con clude that treatment with appropriately timed donor-specific transfusi on and anti-CD154 mAb induces durable survival of both islet and skin xenografts in mice. Because this procedure is targeted directly at CD1 54, a co-activation molecule expressed predominantly by activated CD4( +) T-cells, the results suggest that CD4(+) cells have a major role in the cellular immune response to xenografts.