Genital Tract and Circulating CD8+ T Cell Phenotypes Vary Across the Menstrual Cycle

The menstrual cycle consists of two main phases: the follicular phase, characterized by rising estradiol and low progesterone, and the luteal phase, marked by elevated progesterone following ovulation. Changes in sex hormones have profound physiological effects, yet their impact on immunity remains poorly understood. The prevailing theory suggests that reduced immunity during the luteal phase facilitates embryo implantation but also increases susceptibility to infections. Thus, defining the impact of the menstrual cycle on genital and systemic immunity is critical to understanding how immunity at different sites may be affected.

We examined phenotypic differences in T cells from ectocervical and vaginal tissue biopsies and blood samples collected from 58 women in the follicular phase and 20 women in the luteal phase using flow cytometry and measured seventy-one cytokines and chemokines from serum and cervicovaginal secretions.

The proportions of CD8+ memory T cell subsets varied with menstrual phase, with a higher frequency of central memory cells during the luteal phase and more TEMRA cells during the follicular phase. Cervical CD8+ T cells exhibited higher frequencies of CD38 and CD39 during the luteal phase. We found higher CCL15 and IL-2 concentrations in cervicovaginal fluid, and higher CXCL12 in serum, during the follicular phase. During the luteal phase, CXCL13 was higher in cervicovaginal secretions.

Our findings provide insight into how menstrual phase modulates genital CD8+ T cell phenotypes and memory subsets throughout the cycle and may influence immunity in distinct tissue compartments with consequences for local infection vulnerability.