Influence of islet and bone marrow transplantation on the diabetes and immunodeficiency of BB rats.

The results of islet transplantation in spontaneous autoimmune diabetes of BB rats were studied to determine whether this disease process might damage the transplanted islet tissue. Since BB rats are not genetically uniform, syngenetic grafts could not be used; therefore, allograft rejection was prevented by rendering BB rats immunologically tolerant of WF transplantation antigens by neonatal inoculation with bone marrow cells. Despite the resultant tolerant state, which permitted successful engraftment of WF skin allografts, the transplanted islets ameliorated the spontaneous diabetes of BB rats only briefly before they were destroyed by immune insulitis. BB rats from the diabetic stock were found to suffer from abnormalities in T lymphocytes and their subsets as well as defective immune response patterns. When analyzed with monoclonal antibodies specific for rat lymphocyte markers, BB rats of the diabetic stock were found to be lymphocytopenic. There was a reduction in helper T cells and a more severe deficit in the suppressor/cytotoxic subset. BB rats that were inoculated neonatally with bone marrow from normal donors were found to have a strikingly reduced incidence of diabetes. Moreover, the T cell functional, numerical, and microenvironmental defects that were present in noninoculated BB rats were restored in marrow-inoculated BB rats, findings possibly related to the decreased incidence of diabetes.