Abstract Background Chlamydia trachomatis remains the most prevalent bacterial sexually transmitted infection worldwide, with adolescent girls and young women (AGYW) disproportionately affected. Vaccine development is hindered by limited understanding of protective immunity, particularly in the context of multiple exposures and immune-mediated pathology. Methods We characterised mucosal inflammation and systemic immune responses to C. trachomatis in South African AGYW (n=145), stratified by exposure history based on nucleic acid amplification testing (NAAT) and anti-C. trachomatis IgG (Ab). Cervicovaginal cytokines were quantified from menstrual cup secretions, and cervical T cell activation assessed by flow cytometry. Peripheral CD4+ T cell responses to C. trachomatis were measured in 46 women who were NAAT-positive and/or seropositive. Results A NAAT+/Ab+ status, signifying untreated/recurrent infection, was associated with increased cervical T cell activation. These women all had detectable C. trachomatis-specific CD4+ T cells in blood; however, the magnitude of the response was 2.4-fold lower than in NAAT-/Ab+ or NAAT+/Ab- women, who were considered to have a cleared or primary infection, respectively. The highest proportions of C. trachomatis-specific multifunctional CD4+ T cells were found in NAAT-/Ab+ women, while those who were NAAT+/Ab+ had almost none. Notably, systemic C. trachomatis-specific Th1 responses were overall inversely correlated with genital tract concentrations of inflammatory cytokines including IL-1β, TNF, and IL-17A. Conclusions These findings demonstrate that both the magnitude and quality of the systemic CD4+ T cell responses are critical components of protective immunity to C. trachomatis, and may limit mucosal immunopathology, which has important implications for vaccine strategies and evaluation in high-risk populations.
Bunjun et al. (Fri,) studied this question.