The impact of menstruation on tissue resident memory t cell durability

The National Institute of Child Health and Human Development awarded Emory University $609,863 in project grant funding (R01HD116985) on June 23, 2026, to investigate how menstruation affects tissue-resident memory T cell durability in response to Chlamydia trachomatis infection. The research examines how menstrual cycle–driven immune and tissue remodeling in the female reproductive tract compromises cellular immunity against genitourinary pathogens, with the goal of informing vaccine development that generates long-lived resident memory T cells in cervicovaginal and uterine mucosa to prevent chlamydial infection, reinfection, and associated complications including infertility, ectopic pregnancy, and pelvic pain. The award falls under the Child Health and Human Development Extramural Research program (CFDA 93.865). Performance runs through March 31, 2031, with place of performance in Atlanta, Georgia.

Abstract

Although the vast majority of women and adolescent girls of reproductive age experience periodic menstruation, how this immune-mediated tissue remodeling process compromises cellular immunity generated against genitourinary pathogens, including chlamydia trachomatis (c. Trachomatis), is poorly understood. C. Trachomatis is the causative agent of one of the most costly and common bacterial sexually transmitted infections (stis), with the highest incidence occurring in women and adolescent girls of reproductive age. Genital chlamydial infections can lead to severe diseases and health complications, including congenital transmissions, ectopic pregnancies, infertility, and chronic pelvic pain. Moreover, chlamydial infections increase the risk of acquiring more severe secondary infections. Taken together, these facts emphasize the critical need for an effective vaccine to support mucosal immunity in the FRT. Memory t cells that become localized in the cervicovaginal and uterine mucosa through a recent infection or from vaccination provide optimal immune protection against chlamydial infections, leading to more rapid bacterial clearance and reducing disease severity. Therefore, generating long-lived resident memory t cells in the reproductive tract mucosa that will recognize and respond against c. Trachomatis is a promising approach to strengthening immunity. Previous scientific research investigations into understanding tissue-resident memory t cell durability demonstrate that local environmental molecular signals can provide critical support that determines tissue-resident memory t cell development, regionalization, and prolonged viability at sites such as the lung, skin, and GUT. Yet, despite the fact that genital chlamydial reinfections in women and adolescent girls of reproductive age are common and there is no available vaccine, we have a very limited understanding of how menstruation alters the reproductive tract environment to drive the depletion of pre-existing t cell immunity. Therefore, a major challenge for developing prophylactic strategies, including vaccines that can prevent genital infections, is determining how to support long-lived and durable tissue-resident memory t cells in the reproductive tract under menstrual cycle regulation. The goals of our proposal are to acquire critical insights into the mechanism(s) by which menstruation regulates memory t cell function and identify strategies that can support optimal memory t cell durability against chlamydial infections in cervicovaginal and uterine tissues throughout this process.