Donor modification leads to prolonged survival of limb allografts

Chronic immunosuppression is essential for maintaining human hand transplan t survival because composite tissue allografts are as susceptible to reject ion as visceral organ allografts. Limb allografts comprise different types of tissues with varying antigenicities, and the immunosuppressive doses req uired for these allografts are as high or higher than those required for so lid organ allotransplantation. In particular, bone marrow is all early targ et of the host immune response. This study reports on donor limb modificati on of the marrow compartment leading to prolonged survival of limb allograf ts. Chimeric limb allografts comprising a Lewis rat vascularized allograft and Brown Norway rat bone marrow were created. These chimeric limbs were transp lanted into three recipients: (1) Buffalo rats (n = 12), where the chimeric limb was allogeneic for both vascular graft and bone marrow; (2) Lewis rat s (n = 12), where the limb was allogeneic for marrow alone; and (3) Brown N orway rats (n = 12), where the limb was allogeneic for graft alone. This study found that Brown Norway recipients elicited significantly reduce d cell-mediated and humoral immune responses in comparison with the Buffalo and Lewis recipients (p < 0.001 and p < 0.01, respectively). The Buffalo a nd Lewis recipients both elicited high cell-mediated and humoral responses. The Brown Norway recipients also had prolonged survival of limb tissue all ograft ill comparison with the other experimental groups.