Within the human female reproductive tract (FRT), the challenge of protection against sexually transmitted infections (STIs) is coupled with the need to enable successful reproduction. Oestradiol and progesterone, which are secreted during the menstrual cycle, affect epithelial cells, fibroblasts and immune cells in the FRT to modify their functions and hence the individual’s susceptibility to STIs in ways that are unique to specific sites in the FRT. The innate and adaptive immune systems are under hormonal control, and immune protection in the FRT varies with the phase of the menstrual cycle. Immune protection is dampened during the secretory phase of the cycle to optimize conditions for fertilization and pregnancy, which creates a ‘window of vulnerability’ during which potential pathogens can enter and infect the FRT.

No abstract

Prevention of sexual acquisition of HIV in women requires a substantial increase in our knowledge about HIV-target cell availability and regulation in the female reproductive tract (FRT). In this study, we analyzed the phenotype and susceptibility to HIV-infection of CD4+ T cell in the endometrium (EM), endocervix (END) and ectocervix (ECT) of the FRT. We found that Th17 cells represent a major subset in FRT tissues analyzed, and that Th17 cells were the main CD4+ T cell population expressing CCR5 and CD90. In pre-menopausal women, CD4+ T cells and Th17 cells in particular, were significantly lower in EM relative to END and ECT. Th17 cells were elevated in EM from post-menopausal women relative to pre-menopausal tissues, but not changed in END and ECT. Susceptibility of CD4+ T cells to HIV infection measured as intracellular p24 was lowest in the EM and highest in ECT. Additionally, we found that Th17 cells co-expressing CCR5 and CD90 were the most susceptible to HIV-infection. Our results provide valuable information for designing preventive strategies directed at targeting highly susceptible target cells in the FRT.

Pregnancy-associated changes to steady state serum cytokines may have important immunologic consequence.