Prolonged survival of vascularized limb tissue allografts by donor irradiation

The clinical feasibility of transplantation of a vascularized limb tissue allograft depends upon reducing immunosuppression and its associated toxicity for the graft recipient. Donor or allograft irradiation would eradicate allogeneic marrow and provide a possible alternative or beneficial addition to host immunosuppression. The effect of irradiation on survival of limb tissue allograft was investigated in this study. In a rat model, knee allografts consisting of bone, cartilage, and soft tissues were transplanted across a strong histocompatibility barrier by femoral vascular microanastomoses. The grafts were harvested 1 and 2 weeks postoperatively for histologic and immunologic assays. Gamma irradiation of the graft immediately before transplant decreased graft rejection slightly. However, total body irradiation of the donor followed by a "waiting period" of 2 or more days before transplant significantly delayed rejection. After such a 6-day and a 2-day pretreatment protocol, the host cellular immune responses were not observed 1 and 2 weeks after transplantation and eventual progression toward graft rejection coincided with emergence of host antibody production. Rejection of vascularized limb tissue allografts after donor irradiation thus appeared to be mediated primarily through the humoral pathway. We conclude that donor irradiation is a potentially useful adjunct in prolonging survival of vascularized limb tissue allografts.