Long-term islet allograft function in the absence of chronic immunosuppression: A case report of a nonhuman primate previously made tolerant to a renal allograft from the same donor

Development of mixed chimerism by donor bone marrow transplantation (DBMT) has led to long-term tolerance of solid organ allografts in nonhuman primat es. As an initial attempt to extend this approach to cellular transplant, i slet transplant from the same donor was attempted in the recipient previous ly made tolerant to a kidney allograft. Methods. After the conditioning with ATG, total body irradiation, thymic ir radiation, and splenectomy, DBMT was performed followed by 4 weeks of cyclo sporine. Kidney transplantation and native nephrectomies were subsequently performed on day 89. After 2.8 years of DBMT, diabetes was induced by strep tozocin (STZ) and islets from bone marrow and kidney donor were transplante d without immunosuppression. Results. After DBMT, the recipient developed chimerism and no evidence of k idney rejection for more than 1000 days. STZ induced diabetes was reversed after the islet transplantation. Islet biopsies demonstrated insulin staini ng without rejection. Although the recipient became diabetic 300 days after islet transplantation, viable transplanted islets were found in the liver and under the kidney capsule without any evidence of rejection. Conclusion. Tolerance with a nonmyeloablative conditioning can allow succes sful pancreatic islet transplantation without immunosuppression. Because no histological evidence of rejection was identified, recurrent diabetes is p resumed to be inadequate islet mass.