Characterization of Islet Infiltrating Lymphocytes in NOD mice

Abstract

Nonobese diabetic (NOD) mice are a major animal model for the study of Type 1 diabetes (TID). However, the lymphocytes infiltrating the islets are not well characterized because of low cell numbers. A detailed analysis of the islet infiltrating lymphocytes was carried out using 9 color flow cytometry. Interestingly, up to 30% of the CD4+ T cells and 40% of the CD8+ T cells infiltrating the islets were CD62Lhi and CD44lo indicating a naïve phenotype. In contrast, islet infiltrating CD8+ T cells with specificity for islet‐specific glucose‐6‐phosphatase catalytic subunit‐related protein (IGRP) had an effector phenotype. As the number of CD4+T cells per islet increased the relative number of CD8+ T cells also increased. The percentage of naïve CD4+T cells increased from less than 10% to 30% of the CD4+ T cell population and the percentage of IL‐4+ CD4+ T cells fell, although the number per islet increased linearly with the increase in CD4+ T cells per islet. We concluded that infiltrates with the same number of cells per islet had the same composition regardless of source, i.e. male or female NOD mice. There was a significant difference in the time to reach the same cell number, with females accumulating cells at an earlier age.Research support ‐ NIAID