The impact of reproductive hormones on T cell immunity; normal and assisted reproductive cycles

During pregnancy, a unique immune milieu is established systemically and locally at the maternal-fetal interface. While preparing for embryonic implantation, endometrial effectors significantly change their proportions and function, which are synchronized with hormonal changes. During assisted reproductive technology cycles, various cytokines, chemokines, and immune factors dynamically change with the altered receptor expressions on the immune effectors. Thus, the hormonal regulation of immune effectors is critical to maintaining the immune milieu. In this review, hormonal effects on T cell subsets are reviewed. Sex hormones affect T cell ontogeny and development, consequently affecting their functions. Like other T cell subsets, CD4+ T helper (Th) cells are modulated by estrogen, where low estrogen concentration promotes Th1-driven cell-mediated immunity in the uterus and in vitro by enhancing IFN-γ production, while a high estrogen level decreases it. The abundance and differentiation of T regulatory (Treg) cells are controlled by estrogen, inducing Treg expansion. Conversely, progesterone maintains immune homeostasis by balancing Th1/Th2 and Th17/Treg immunity, leading to maternal-fetal tolerance. Therefore, the understanding of the hormonal impact on various T cell subsets during the reproductive cycles is critical to improving reproductive outcomes in women with recurrent pregnancy losses, repeated implantation failures, and undergoing assisted reproductive cycles.