Intrathymic transplantation of allogeneic perinatal islets does not induce donor-specific tolerance

Intrathymic transplantation of adult rat collagenase-isolated islets has been shown to induce tolerance to a subsequent allograft of donor islets to the renal subcapsular site. This suggests that donor-specific tolerance is induced by the presence of foreign antigens in the thymus and the thymus' role in immune "education." Studies have followed demonstrating that tolerance may be achieved by intrathymic transplantation of a diverse array of tissues. The parenchyma of the tissue does not seem to be important, since tolerance is achieved following intrathymic transplantation of spleen cells and hepatocytes, which do not survive at the intrathymic site. Neonatal rat islets isolated using a nonenzymatic, in vitro technique are nonimmunogenic and freely transplantable to nonimmunosuppressed, allogeneic recipients. The nonimmunogenicity of the neonatal islets is suggested to be due to the absence of MHC class II-positive APCs in the islets. The neonatal islet allografts are targeted by a rejection response that is initiated by immunogenic donor tissue, such as spleen cells, isolated dendritic cells, or the cellular "debris" obtained in the in vitro isolation technique. We have reported previously that intrathymic transplantation of the neonatal islets does not induce tolerance to a subsequent renal subcapsular allograft of collagenase-isolated adult rat islets. Since the islets are nonimmunogenic in allogeneic transplantation, they offer the necessary control to determine the effect of antilymphocyte serum (ALS) on development of tolerance. This report includes the results of the effect of ALS on the induction of tolerance by intrathymic transplantation of nonimmunogenic neonatal islets.