Treatment With Anti-T-Lymphocyte Antibodies Prevents Induction of Insulitis in Mice Given Multiple Doses of Streptozocin

Abstract

The importance of T-lymphocytes in the induction of insulitis and hyperglycemia in certain strains of mice treated with multiple subdiabetogenic doses of streptozocin has been a matter of controversy. To understand the role of T-lymphocytes, we treated thymectomized BALB/c ByJ mice with five daily doses of streptozocin (45 mg/kg) and determined the effect of treatment with monoclonal antibodies against T-lymphocyte subsets on the development of diabetes and insulitis. Hyperglycemia (mean glucose of 321 ± 29 vs. 167 ± 15 mg/dl in controls) and insulitis were induced in BALB/c ByJ mice given streptozocin. Thy1.2+, L3T4+, and Lyt2+ cells were all identified within the islets of diabetic mice. There was a relative paucity of L3T4+ cells and an overabundance of Lyt2+ cells compared with the frequency of these cells found in lymphatic tissues or peripheral blood. Treatment with anti-L3T4 or anti-Lyt2 monoclonal antibodies caused a reduction in splenic T-lymphocyte subsets and attenuated the hyperglycemia to 212 ± 14 and 197 ± 16 mg/dl (P < .001 and .01), respectively, compared with controls and prevented the insulitis induced by streptozocin. Our studies support the hypothesis that an immune response is important to the development of multi–low-dose streptozocin diabetes and indicate that treatment with monoclonal antibodies against the L3T4+ or Lyt2+ T-lymphocyte subsets can attenuate this process.