Combination of anti-CD25 antibody and poly I:C treatment in pregnant NOD mice may be used as ‘pregnancy-related’ type 1 diabetes model

Abstract

Aims/Introduction: Some women develop type 1 diabetes during pregnancy or immediately after delivery. However, the underlying pathophysiology remains largely unknown, probably because of the lack of a suitable animal model. In this study, we administered pregnant NOD mice with an anti-CD25 antibody to reduce regulatory T cells along with poly I:C and examined the onset of diabetes. Materials and Methods: Anti-CD25 antibody and poly I:C were intraperitoneally administered to mated female NOD mice. Mice delivered within 3 weeks after the treatment, and the onset of diabetes during pregnancy or within 6 weeks after delivery was examined. Some mice were killed 1 week after treatment, and their spleen and pancreas were excised to examine the expression levels of cytokines and for histological examination. Results: Half of the mice treated with anti-CD25 antibody plus poly I:C developed diabetes, as compared with none of the poly I:C-injected mice (P < 0.05). The ratios of interleukin-18/forkhead box P3 and granzyme B/forkhead box P3 were higher in the pancreas of anti-CD25 antibody plus poly I:C-treated mice than in the pancreas of control mice. The insulitis score decreased in the pancreas of anti-CD25 antibody plus poly I:C-injected pregnant NOD mice. Conclusions: We describe the use of anti-CD25 antibody to reduce regulatory T cells and poly I:C as a Toll-like receptor 3 stimulator to mimic viral infection in a pregnant NOD mouse, which can be used as a model of ‘pregnancy-related’ type 1 diabetes.