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

## TL;DR

This study shows that T cell responses to Chlamydia trachomatis in South African adolescent girls and young women are linked to infection status and inflammation, offering insights for vaccine development.

## Contribution

The study identifies how T cell immunity correlates with infection outcomes and inflammation in a high-risk population.

## Key findings

- C. trachomatis-specific CD4+ T cell responses were lower in untreated/recurrent infections compared to cleared or primary infections.
- Systemic Th1 responses were inversely correlated with genital inflammation, suggesting a protective role.
- Polyfunctional Th1 cells were nearly absent in untreated infections, highlighting their importance in immunity.

## 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.

C. trachomatis-specific Th1 responses were associated with lower mucosal inflammation, while exposure was associated with fewer polyfunctional Th1 cells. Findings suggest that both the magnitude and quality of T cell responses are key requirements for protective immunity and limiting immunopathology.