The results of islet transplantation in an animal model of spontaneous immune insulitis were studied to see whether this disease process might damage transplanted tissue. Since the insulitis occurs only in “BB” rats (which are not genetically uniform) syngeneic grafts could not be used, therefore allograft rejection was avoided by rendering “BB” rats tolerant of WF transplantation antigens by inoculating them neonatally with WF bone marrow cells. Despite the resultant tolerant state, which permitted successful engraftment of WF skin and islets transplanted to artificially diabetic “BB” rats, tolerant “BB” rats with spontaneous diabetes accepted transplanted WF islets only briefly before they were destroyed by immune insulitis.
“BB” rats were found to have abnormalities in immune response (delayed skin graft rejection and decreased alloreactivity in mixed lymphocyte response). However, the immune response was more normal in “BB” rats that were treated neonatally with WF bone marrow. Moreover, “BB” rats inoculated with WF bone marrow neonatally were found less likely to become diabetic than untreated “BB” controls. It is suggested that the chimeric state (persistence of WF bone marrow cells) may be responsible for the improved immune response and perhaps for the decreased susceptibility to diabetes.
