Abstract
Using four core genotypes (FCG) mice, we have previously shown a larger number of CD4(+) and CD8(+) T cells in the spleens of female mice, a sex difference that develops by postnatal day 7 and is retained through adulthood. This difference in splenic T cell number is a consequence of reduced thymic egress and reduced splenic seeding in male mice, caused in part by the male-specific perinatal surge of testosterone, and in part by Sry, which is overexpressed in this model. Here, we used the background strain for FCG mice (C57BL/6J) to ask whether sex influenced actual immunity in the postnatal period. Pups were immunized on postpartum days 1 or 3 with Mycobacterium tuberculosis (Mtb), challenged on day 7 with Mtb purified protein derivative (PPD), and sacrificed on day 8. Subsequent ex vivo challenges of splenocytes showed PPD-stimulated CD8(+) responses (increased CD8(+), increased CD8(+)CD44(hi), decreased CD8(+)CD44(hi)CD127(-/lo)) but no differences between males and females. However, when CD8(+) T cells were analyzed for IFN-γ and IL-2 production, although there was no sex difference in mono-functional IFN-γ(+) (100%) or IL-2(+) (67%), only females (0% of males and 42% of females) produced bi-functional (IFN-γ(+)IL-2(+)) cells. Ex vivo PPD-stimulated responses of other relevant cells from the spleen showed no sex differences in dendritic cells (CD11c(+)CD86(+)IL-6(+)) but females had more (3-fold) IL-6-producing macrophages (F4/80(+)CD86(+)IL-6(+)) and reduced T regulatory cells (CD4(+)CD25(+)Foxp3(+)). We conclude that some sex differences in immunity are evident at one week of age in Mtb immunized mouse pups, with females exhibiting qualitatively superior Mtb-specific immune responses.