Characterization of CD8⁺ T cell subsets in male and female non-obese diabetic mice

To compare and analyze the differences in CD8⁺ naive, effector, memory, exhausted and regulatory T cells in order to investigate the impact of gender on the differentiation fate of CD8⁺ T cells in the context of type 1 diabetes (T1D) based on female and male non-obese diabetic (NOD) mice and healthy Institute for Cancer Research (ICR) mice.

The frequencies and phenotypes of CD8⁺ T cell differentiation subsets including naive T cells (T_N), central memory T cells (T_CM), effector T cells (T_EFF), effector precursor T cells (T_EP), exhausted T cells (T_EX), precursor exhausted T cells (T_PEX) and regulatory T cells (Tregs) in the spleen, pancreatic draining lymph nodes (pLN) and pancreas infiltrating lymphocytes (PIL) of male and female NOD mice were detected by flow cytometry.

The frequencies of IFN-γ⁺, CD107a⁺ and CCL5⁺ CD8⁺ T_EFF in pLN and PIL of female NOD mice were significantly higher than those of male NOD mice. However, the frequencies of CD8⁺ T_N, CD8⁺ T_CM, CD8⁺ T_EX, CD8⁺ T_PEX and CD122⁺CD8⁺ Tregs subsets in the spleen were significantly decreased. While there were no significant differences in the above CD8⁺ T cell subsets except CD8⁺ Tregs between female and male ICR mice.

Androgen may inhibit the differentiation of memory T cells into effector T cells and promote the exhaustion of effector T cells, leading to the difference in morbidity between the male and female mice.