THE FAILURE OF INTRATHYMIC TRANSPLANTATION OF NONIMMUNOGENIC ISLET ALLOGRAFTS TO PROMOTE INDUCTION OF DONOR-SPECIFIC UNRESPONSIVENESS

Freshly isolated allogenic pancreatic islets transplanted into the thy mus of transiently immunosuppressed rats are not rejected but survive indefinitely while also inducing a state of specific unresponsiveness that permits survival of secondary donor-strain islets transplanted ex trathymically. Since freshly isolated pancreatic islets contain intrai slet antigen-presenting cells as well as endocrine cells it is unclear which cellular component is primarily responsible for mediating unres ponsiveness. We therefore examined the impact of pretransplant in vitr o culture (a maneuver which selectively depletes intraislet APCs) on t he capacity of islet allografts to induce unresponsiveness after intra thymic implantation. APC-depleted pancreatic islets, which are known t o have reduced immunogenicity, survived indefinitely in the thymus of allogeneic hosts whether or not brief immunosuppression was employed, but failed to promote survival of subsequent donor-strain islets trans planted to an extrathymic site. These findings emphasize the central r ole of APCs in the induction of transplantation tolerance in this mode l, and are consistent with the established role of this population in the development of T cell tolerance in the thymus.