T cell signatures associated with reduced Chlamydia trachomatis reinfection in a highly exposed cohort
Kacy S. Yount, Chi-Jane Chen, Avinash Kollipara, Chuwen Liu, Neha V. Mokashi, Xiaojing Zheng, C. Bruce Bagwell, Taylor B. Poston, Harold C. Wiesenfeld, Sharon L. Hillier, Catherine M. O’Connell, Natalie Stanley, Toni Darville
Kacy S. Yount, Chi-Jane Chen, Avinash Kollipara, Chuwen Liu, Neha V. Mokashi, Xiaojing Zheng, C. Bruce Bagwell, Taylor B. Poston, Harold C. Wiesenfeld, Sharon L. Hillier, Catherine M. O’Connell, Natalie Stanley, Toni Darville
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Research Article Immunology Infectious disease

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

Abstract

Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection globally. Understanding natural immunity to CT will inform vaccine design. This study aimed to profile immune cells and associated functional features in CT-infected women and determine immune profiles associated with reduced risk of ascended endometrial CT infection and CT reinfection. PBMCs from CT-exposed women were profiled by mass cytometry, and random forest models identified key features that distinguished outcomes. CT+ participants exhibited higher frequencies of CD4+ Th2, Th17, and Th17 double-negative (Th17 DN) CD4+ T effector memory (TEM) cells than uninfected participants with decreased expression of T cell activation and differentiation markers. Minimal differences were detected between women with or without endometrial CT infection. Participants who remained follow-up negative (FU–) showed higher frequencies of CD4+ T central memory (TCM) Th1, Th17, Th1/17, and Th17 DN but reduced CD4+ TEM Th2 cells than FU+ participants. Expression of markers associated with central memory and Th17 lineage was increased on T cell subsets among FU– participants. These data indicate that peripheral T cells exhibit distinct features associated with resistance to CT reinfection. The highly plastic Th17 lineage appears to contribute to protection. Addressing these immune nuances could promote efficacy of CT vaccines.

Authors

Kacy S. Yount, Chi-Jane Chen, Avinash Kollipara, Chuwen Liu, Neha V. Mokashi, Xiaojing Zheng, C. Bruce Bagwell, Taylor B. Poston, Harold C. Wiesenfeld, Sharon L. Hillier, Catherine M. O’Connell, Natalie Stanley, Toni Darville

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Figure 4

CT+ and CT+CoP participants express reduced T cell activation and differentiation markers on several CD4+ and CD8+ subsets compared with uninfected participants.

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CT+ and CT+CoP participants express reduced T cell activation and differ...
A random forest model trained on (A) CD4+ or (H) CD8+ manually gated subset frequency features and upper quartile expression features was used to discriminate between uninfected, CT+, and CT+CoP outcomes at enrollment (En) or 1 month (1M). Receiver operating characteristic (ROC) curves describe performance of the model. Top informative markers of (B–G) CD4+ or (I–M) CD8+ T cells were identified by feature importance analysis at En (see Supplemental Tables 6 and 7 for additional features and 1M analysis). Features were included on the plot if they were statistically significant (as defined by P < 0.001 by Wilcoxon rank sum test between outcomes) for at least 1 comparison between uninfected versus CT+ or uninfected versus CT+CoP. Box plots represent the overall distribution of marker expression. Individual points represent the upper quartile expression for each participant in the group. AUC, area under the ROC curve.