Islet lymphocyte subsets in male and female NOD mice are qualitatively similar but quantitatively distinct

Abstract

Islet-infiltrating lymphocytes of individual male and female non-obese diabetic (NOD) mice were examined with the purpose of determining the differences that lead to a predominance of diabetes in female versus males NOD mice. When normalized for the amount of islet lymphocytes recovered, the infiltrating lymphocytes of female NOD mice were indistinguishable from those of male NOD mice. The only observed difference was that islet inflammation progressed at an increased rate in female compared to male NOD mice. There was no difference in the composition of islet infiltrates in male and female NOD mice. Unexpectedly, the ratio of CD4⁺:CD8⁺ T cells was tightly controlled in the islets throughout diabetogenesis. The frequency of IL-4⁺ CD4⁺ T cells started high but quickly fell to 3% of the population that was maintained with increasing inflammation. A significant portion of the CD8⁺ T cells were islet-specific glucose-6-phosphatase catalytic subunit-related protein specific in both male and female NOD mice and this population was antigen experienced and increased at high levels of islet inflammation. Surprisingly, a large pool of antigen inexperienced naïve T cells was detected in the islets. We conclude the underlying immunological processes in both male and female NOD mice are similar while the rates differ and the presence of naïve T cell in the islets may contribute to epitope spreading.

Keywords::

• Autoimmunity
• FoxP3
• IGRP
• IL-4
• naïve T-cell

Acknowledgements

The expertise and assistance of Lucinda Hensley, Shaun Steel, Corey Morris and Michael Johnson was invaluable. This research is supported in part by National Institutes of Health Grants AI 0524354, AI052435-03S1, AI058014 and AI54843 and Grant 1-2008-24 from the Juvenile Diabetes Research Foundation. The work described in this article was carried out in accordance with the EC Directive 86/609/EEC for animal experiments and The Uniform Requirements for Manuscripts Submitted to Biomedical Journals.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.