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

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.