Unique T cell signatures are associated with reduced Chlamydia trachomatis reinfection in a highly exposed cohort.

Abstract

Abstract Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection (STI) in the U.S. despite effective antibiotics. Understanding natural immunity to CT is crucial to inform vaccine design. This study aimed to identify immune cell populations and functional features associated with reduced risk of CT reinfection. PBMCs were collected from 82 CT-exposed women tested for CT and other STIs upon enrollment, and repeatedly over 1 year of follow-up. Immune responses were profiled by mass cytometry. Women with CT at enrollment exhibited higher frequencies of CD4+ effector memory T cells (TEM) than uninfected women. Specifically, Th2, Th17, and Th17 DN CD4 TEM were increased. However, functional features indicated diminished expression of T cell activation and differentiation markers, underscoring weaknesses of natural immunity that could be addressed by vaccine design. Comparing responses in women who remained follow-up negative (FU-) to those who were reinfected (FU+), higher frequencies of Th1, Th17, and Th17 DN CD4 T cells were observed in FU- women. Conversely, Th2 CD4 T cells were increased in FU+ women. Furthermore, markers of T cell differentiation, memory, and cytotoxicity were increased in FU- women. These data indicate that peripheral T cells exhibit distinct features associated with natural immunity to CT. Notably, the highly plastic Th17 lineage appears to contribute to protection. Addressing these immune nuances could promote efficacy of CT vaccines.