Anti-interleukin 2 receptor antibody attenuates low-dose streptozotocin-induced diabetes in mice

Recent evidence indicates that activated T cells and macrophages play an important role in the induction of insulitis and diabetes in certain strains of mice treated with multiple subdiabetogenic doses of streptozotocin. In the present study, we treated C57BL/6J mice with five daily doses of 40 mg/ml streptozotocin and examined the prophylactic effect of an anti-interleukin 2 receptor monoclonal antibody (PC61). In mice treated with streptozotocin, interleukin 2 receptor-positive mononuclear cells were shown to infiltrate into the islets and soluble interleukin 2 receptors in the sera were significantly increased compared with control mice. The administration of PC61 to the mice attenuated the insulitis, and diminished interleukin 2 receptor-positive cells from islets and soluble interleukin 2 receptors in the sera. Moreover, the administration of PC61 significantly reduced the development of hyperglycaemia shown in these mice (12.8 +/- 1.1 mmol/l vs 18.5 +/- 0.7 mmol/l, p less than 0.005). As judged by flow cytometric analysis, this antibody did not cause any changes in either spleen cell counts or T cell subsets. Interleukin 2 receptors were expressed on a minor population of spleen cells regardless of treatment with PC61 (STZ + normal rat IgG: 2.1 +/- 0.3%, STZ + PC61: 2.4 +/- 0.3%). Even after stimulation of spleen cells with concanavalin A or alloantigen, interleukin 2 receptor expression was not significantly different between the two groups. Our studies suggest that interleukin 2 receptor-positive activated T cells or macrophages are important in the development of multi-low-dose streptozotocin diabetes and that an anti-interleukin 2 receptor antibody can attenuate this process.