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 3

CD4 but not CD8 automated gating frequency features differentiate CT+ and CT+CoP participants from uninfected participants.

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CD4 but not CD8 automated gating frequency features differentiate CT+ an...
(A–F) Automated gating by k-means clustering and cluster annotation. (A and B) Expression of phenotypic markers (CD45RA, CCR7, CD95, CCR6, CXCR3, and CCR4) was used to partition CD4+ T cells into 25 k-means clusters. (C) Resulting CD4+ clusters were annotated based on marker expression (see Supplemental Tables 4 and 5). (D and E) CD8+ T cells were partitioned into 25 k-means clusters based on the expression of the same phenotypic markers as for CD4+ T cells and (F) were annotated. (G) Box plots representing frequencies of CD4+ clusters with significant differences in frequency (Wilcoxon P < 0.05). Statistical comparisons between CT+ or CT+CoP and uninfected by Wilcoxon test. Significance symbols are defined as *P < 0.05, **P < 0.01, ***P < 0.001. White triangle represents mean. TSNE, t-distributed stochastic neighbor embedding.