Effect Of Sex On Cellular Immunity

Females exhibit more robust cellular immune responses to vaccination than males. Studies in rodents have demonstrated that sex differences in immunity arise because of differences in gonadal hormone levels between the sexes. The higher androgen levels in males result in a steeper decline in thymic output postpuberty. In contrast, females have a higher thymic output resulting in a larger pool of naive T cells that can respond to antigenic stimulation. There is also evidence that female and male naive T cells respond differently to vaccination. Female T cells not only proliferate more robustly than male T cells but also secrete higher levels of T-helper 1 (Th1) cytokines. These sex differences are largely due to effects of androgens in limiting T cell responses in males. Androgens dampen Th1 immune responses by promoting IL-10 production by antigen-presenting cells, inhibiting IFN-gamma gene expression in T cells, and shaping the gut microbiota and host hormone environment. There is evidence that low levels of estradiol, associated with the follicular phase of the menstrual cycle in women, may have a stimulatory effect on certain aspects of cellular immunity. This article will review the key evidence from human and rodent studies that support this view.