Cyclosporine-induced tolerance requires antigens capable of initiating an immune response

We studied two example where indefinite graft survival could be obtained in rats. In the first, strain DA hearts were permanently accepted in allogeneic PVG rats if the recipients were treated for at least 7 consecutive days with cyclosporine A (CsA) after transplantation. In the second, DA pancreatic islets were permanently accepted in PVG rats if the islets were cultured in vitro for 14 days in high oxygen. When cultured islet-grafted PVG rats were injected with lymphocytes from other PVG rats previously sensitized to DA alloantigens, the islet grafts were destroyed within 14 days. By contrast, it was difficult to cause the DA heart allografts to cease beating with the same adoptive transfer protocol; approximately two-thirds of the heart-grafted animals maintained their grafts. This difference was not due to the CsA as cultured islets transplanted in the presence of CsA were still susceptible to rejection by sensitized lymphocytes. However, islets that had not been cultured in high oxygen prior to transplantation and that were maintained with CsA were not rejected after the injection of sensitized lymphocytes. These results suggest that CsA can most readily induce a state of tolerance when the graft is capable of initiating an immune response.