Diabetes, Vol 36, Issue 7 796-801, Copyright © 1987 by American Diabetes Association

ARTICLES

Treatment with anti-T-lymphocyte antibodies prevents induction of insulitis in mice given multiple doses of streptozocin

KC Herold, AG Montag and FW Fitch

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 less than .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.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S.-E. Lamhamedi-Cherradi, S. Zheng, B. A. Hilliard, L. Xu, J. Sun, S. Alsheadat, H.-C. Liou, and Y. H. Chen Transcriptional Regulation of Type I Diabetes by NF-{kappa}B J. Immunol., November 1, 2003; 171(9): 4886 - 4892. [Abstract] [Full Text] [PDF]

				S. Kondo, I. Iwata, K. Anzai, T. Akashi, S. Wakana, K. Ohkubo, H. Katsuta, J. Ono, T. Watanabe, Y. Niho, et al. Suppression of insulitis and diabetes in B cell-deficient mice treated with streptozocin: B cells are essential for the TCR clonotype spreading of islet-infiltrating T cells Int. Immunol., July 1, 2000; 12(7): 1075 - 1083. [Abstract] [Full Text] [PDF]

				A. Sinha, M. Lopez, and H. McDevitt Autoimmune diseases: the failure of self tolerance Science, June 15, 1990; 248(4961): 1380 - 1388. [Abstract] [PDF]