Unique 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 Vivek Mokashi; Xiaojing Zheng; C Bruce Bagwell; Taylor B. Poston; Harold C. Wiesenfeld; Sharon L. Hillier; Catherine M. O'Connell; Natalie Stanley; Toni Darville

doi:10.1172/jci.insight.189388

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

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¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by Chen, C. in: JCI | PubMed | Google Scholar |

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by Kollipara, A. in: JCI | PubMed | Google Scholar

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by Liu, C. in: JCI | PubMed | Google Scholar

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by Mokashi, N. in: JCI | PubMed | Google Scholar

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by Zheng, X. in: JCI | PubMed | Google Scholar |

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by Bagwell, C. in: JCI | PubMed | Google Scholar

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by Poston, T. in: JCI | PubMed | Google Scholar |

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by Wiesenfeld, H. in: JCI | PubMed | Google Scholar |

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by Hillier, S. in: JCI | PubMed | Google Scholar

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by O'Connell, C. in: JCI | PubMed | Google Scholar |

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by Stanley, N. in: JCI | PubMed | Google Scholar

¹Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

²Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

³Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, United States of America

⁴Topsham, United States of America

⁵Magee-Womens Research Institute, The University of Pittsburgh, Pittsburgh, United States of America

Find articles by Darville, T. in: JCI | PubMed | Google Scholar |

JCI Insight. https://doi.org/10.1172/jci.insight.189388.
Copyright © 2025, Yount et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published February 27, 2025 - Version history

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 distinguish outcomes. CT+ participants exhibited higher frequencies of CD4+ Th2, Th17, and 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 were 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.

Version 1 (February 27, 2025): In-Press Preview

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

Kacy S. Yount,¹ Chi-Jane Chen,² Avinash Kollipara,¹ Chuwen Liu,³ Neha Vivek Mokashi,³ Xiaojing Zheng,¹ C Bruce Bagwell,⁴ Taylor B. Poston,¹ Harold C. Wiesenfeld,⁵ Sharon L. Hillier,⁵ Catherine M. O'Connell,¹ Natalie Stanley,² and Toni Darville¹

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

Kacy S. Yount,1 Chi-Jane Chen,2 Avinash Kollipara,1 Chuwen Liu,3 Neha Vivek Mokashi,3 Xiaojing Zheng,1 C Bruce Bagwell,4 Taylor B. Poston,1 Harold C. Wiesenfeld,5 Sharon L. Hillier,5 Catherine M. O'Connell,1 Natalie Stanley,2 and Toni Darville1

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Kacy S. Yount,¹ Chi-Jane Chen,² Avinash Kollipara,¹ Chuwen Liu,³ Neha Vivek Mokashi,³ Xiaojing Zheng,¹ C Bruce Bagwell,⁴ Taylor B. Poston,¹ Harold C. Wiesenfeld,⁵ Sharon L. Hillier,⁵ Catherine M. O'Connell,¹ Natalie Stanley,² and Toni Darville¹