Chlamydia trachomatis-specific T Cell Immunity Reflects Widespread Exposure in South African Adolescents and Young Women.

Abstract

Chlamydia trachomatis remains the most prevalent bacterial sexually transmitted infection worldwide, disproportionately affecting adolescent girls and young women (AGYW). Vaccine development is hindered by a limited understanding of protective immunity, particularly in the context of multiple exposures and immunopathology. We characterized 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 serology (Ab). Specifically, cervicovaginal cytokines, cervical T cell activation, and C. trachomatis-specific CD4+ T cell responses were assessed. 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 + (cleared infection) or NAAT+/Ab- (primary infection) groups. C. trachomatis-specific multifunctional CD4+ T cells were highest in NAAT-/Ab + women, and nearly absent in those who were NAAT+/Ab +. 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. 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, informing vaccine strategies in high-risk populations.