PROLONGED SURVIVAL OF VASCULARIZED LIMB TISSUE ALLOGRAFTS BY DONOR IRRADIATION

The clinical feasibility of transplantation of a vascularized limb tis sue allograft depends upon reducing immunosuppression and its associat ed toxicity for the graft recipient. Donor or allograft irradiation wo uld eradicate allogeneic marrow and provide a possible alternative or beneficial addition to host immunosuppression. The effect of irradiati on on survival of limb tissue allograft was investigated in this study . In a rat model, knee allografts consisting of bone, cartilage, and s oft tissues were transplanted across a strong histocompatibility barri er by femoral vascular microanastomoses. The grafts were harvested 1 a nd 2 weeks postoperatively for histologic and immunologic assays. Gamm a irradiation of the graft immediately before transplant decreased gra ft rejection slightly. However, total body irradiation of the donor fo llowed by a ''waiting period'' of 2 or more days before transplant sig nificantly delayed rejection. After such a 6-day and a 2-day pretreatm ent protocol, the host cellular immune responses were not observed 1 a nd 2 weeks after transplantation and eventual progression toward graft rejection coincided with emergence of host antibody production. Rejec tion of vascularized limb tissue allografts after donor irradiation th us appeared to be mediated primarily through the humoral pathway. We c onclude that donor irradiation is a potentially useful adjunct in prol onging survival of vascularized limb tissue allografts. (C) 1995 Acade mic Press, Inc.