INSULIN-TREATMENT PREVENTS DIABETES-MELLITUS BUT NOT THYROIDITIS IN RT6-DEPLETED DIABETES RESISTANT BB WOR RATS

Prophylactic insulin administration is known to prevent hyperglycaemia in diabetes prone BB rats and nonobese diabetic mice. This study investigated the effect of insulin treatment on the development of overt diabetes, clinically inapparent anti-islet autoreactivity, and thyroiditis in RT6-depleted diabetes resistant BB rats. Fewer than 1% of these animals develop spontaneous diabetes, but if depleted of RT6+ T cells > 50% become hyperglycaemic. We treated 30-day-old diabetes resistant rats with anti-RT6.1 monoclonal antibody, exogenous insulin, or both. Up to 60 days of age, 16 of 20 rats given antibody alone became diabetic, compared with 1 of 20 also treated with antibody plus insulin. Up to 110 days of age, only 1 of 10 rats treated with both insulin and antibody between 30 and 60 days became diabetic. Histologic study of non-diabetic insulin plus anti-RT6 antibody treated rats revealed insulitis in 3 of 9 at 60 days old, and insulitis in 3 of 8 and thyroiditis in 6 of 7 at 110 days of age. Non-diabetic animals were also found to harbour autoreactive spleen cells that adoptively transferred diabetes. Splenocytes from 60 or 110-day-old non-diabetic donors that had been treated with insulin and antibody between 30 and 60 days of age induced diabetes in 7 of 13 and 6 of 8 adoptive recipients respectively. We conclude that insulin treatment prevents clinical diabetes in the RT6-depleted diabetes resistant BB rat, but this treatment does not prevent the development of autoreactive cell populations that cause thyroiditis and adoptively transfer diabetes.