Prevention of recurrent diabetes in syngenic islet-transplanted NOD mice by transfusion of autoreactive T lymphocytes.

Islet transplantation has been considered to be one of the best methods for the cure of type I diabetes, but transplanted islets are eventually destroyed by the host's cell-mediated autoimmune responses unless immunosuppressive agents are given. This investigation was initiated to develop a method for the prevention of beta cell destruction in transplanted islets without the use of immunosuppressive drugs. We have recently cloned CD4+ autoreactive T cells (NY1.1 and NY4.2) from lymphocytes infiltrating the pancreatic islets of nonobese diabetic (NOD*) mice and have shown that these cells respond to self MHC class II determinants. When the T cell clones (10(7) cells of either NY1.1 or NY4.2) were transfused into acutely diabetic NOD mice 2 to 3 days before transplantation of syngenic islets (400) into the subrenal space, the transplanted islets were not destroyed, and the animals maintained normoglycemia over 100 days without insulin treatment. In contrast, NOD mice that received syngenic islets (400) without the transfusion of an autoreactive T cell clone showed a recurrence of diabetes and massive mononuclear cell infiltration of the grafted islets within 17 days. On the basis of these observations, it is concluded that CD4+ autoreactive T lymphocytes can prevent the recurrence of insulitis and development of diabetes in pancreatic islet-transplanted NOD mice, without treatment with immunosuppressive drugs.