POST-THYMECTOMY ORGAN-SPECIFIC AUTOIMMUNITY - ENHANCEMENT BY CYCLOSPORINE-A AND INHIBITION BY IL-2

It has previously been shown that the administration of cyclosporine A to newborn mice results in the development of autoimmunity later in l ife. It has been proposed that the neonatal administration of cyclospo rine A results in altered thymic selection or inhibition of the develo pment of suppressor cells. In the present study, treatment of day 3 th ymectomized C3H/HeN mice with cyclosporine A (20 mg/kg/day) for 9 d po st surgery increased the prevalence of antigastric autoantibodies. In contrast, the administration of IL-2 (300-600 Units/g/day) for 7 days after thymectomy inhibited the development of antigastric antibodies. We hypothesize that CsA may act by causing transient lymphokine abnorm alities in the extrathymic environment during the first few weeks of l ife which lead to the development of antigastric antibodies. In contra st to the inhibition of development of antigastric antibodies, the adm inistration of a similar course of IL-2 produced only a transient supp ression of diabetes in NOD mice. These results and other data suggest that diabetes in NOD mice is probably due to a different immunologic d efect.