Increased T regulatory cells lead to development of Th2 immune response in male SJL mice

Abstract

SJL mice represent a mouse model in which young adult females are susceptible to autoimmune disease, while age-matched males are relatively resistant. T cells primed in female SJL mice secrete cytokines associated with a Th1 phenotype. By contrast, T cells primed in males secrete cytokines associated with a Th2 phenotype. Activation of Th2-type T cells in males vs. Th1 cells in females correlates with increased CD4⁺CD25⁺ T regulatory cells (Treg) in males. T cells primed in males depleted of CD4⁺CD25⁺ T cells preferentially secrete IFN-γ and decreased IL-4 and IL-10 compared to CD4⁺CD25⁺ T-cell-sufficient males, suggesting that Treg influence subsequent antigen-specific cytokine secretion. Treg from males and females exhibit equivalent in vitro T-cell suppression. Treg from males express increased CTLA-4 and CD62L and preferentially secrete IL-10. These data suggest that an increased frequency of IL-10 secreting Treg in male SJL mice may contribute resistance to autoimmune disease by favoring the development of Th2 immune responses.

Keywords::

• autoimmunity
• experimental autoimmune encephalomyelitis
• regulatory T cells
• cytokines
• mice

Acknowledgements

The authors thank Ni Feng, Nermina Covic, and Jeffery Tarcy for technical assistance and Jennifer Powers for cell sorting. This work was supported by National Institutes of Health grant NS 53824.

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