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

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.

Keywords

• NOD mouse
• Pregnancy
• Type 1 diabetes