To determine if the rats that received the PLNC were tolerant, the cyclosporine was discontinued after 75 days. In the other cohorts, the cyclosporine was continued until the conclusion of the experiment. Thus, graft failure in the islet alone group could only be due to autoimmunity. In contrast, addition of donor PLNC prevented autoimmune recurrence in every case. Established islet plus PLNC transplants function for 100 days without immunosuppressions.
Recurrent autoimmunity is an important factor in graft failure even in immunosuppressed recipients.
Successful engraftment of a donor regulatory T cell subset led to abrogation of the autoimmune state as well as tolerance to the donor islets, as evidenced by the successful withdrawal of immunosuppression. BB rats are characterized by a global T cell maturation deficit that facilitates donor T cell engraftment. Nevertheless, the routine success of human pancreas transplants and the results of these experiments suggest that clinical islet transplants may be protected from recurrent autoimmunity by techniques which lead to at least temporary engraftment of donor immuno-regulatory cells.