Distinct Populations of Antigen-specific Tissue-resident CD8+ T Cells in Human Cervix Mucosa

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2021 Jun 22

PMID 34156975

Citations 19

Authors

Tao Peng

Khamsone Phasouk

Emily Bossard

Alexis Klock

Lei Jin

Kerry J Laing

Christine Johnston

Noel A Williams

Julie L Czartoski

Dana Varon

Annalyssa N Long

Jason H Bielas

Thomas M Snyder

Harlan Robins

David M Koelle

M Juliana McElrath

Anna Wald

Lawrence Corey

Jia Zhu

Affiliations

Soon will be listed here.

Abstract

The ectocervix is part of the lower female reproductive tract (FRT), which is susceptible to sexually transmitted infections (STIs). Comprehensive knowledge of the phenotypes and T cell receptor (TCR) repertoire of tissue-resident memory T cells (TRMs) in the human FRT is lacking. We took single-cell RNA-Seq approaches to simultaneously define gene expression and TCR clonotypes of the human ectocervix. There were significantly more CD8+ than CD4+ T cells. Unsupervised clustering and trajectory analysis identified distinct populations of CD8+ T cells with IFNGhiGZMBloCD69hiCD103lo or IFNGloGZMBhiCD69medCD103hi phenotypes. Little overlap was seen between their TCR repertoires. Immunofluorescence staining showed that CD103+CD8+ TRMs were preferentially localized in the epithelium, whereas CD69+CD8+ TRMs were distributed evenly in the epithelium and stroma. Ex vivo assays indicated that up to 14% of cervical CD8+ TRM clonotypes were HSV-2 reactive in HSV-2-seropositive persons, reflecting physiologically relevant localization. Our studies identified subgroups of CD8+ TRMs in the human ectocervix that exhibited distinct expression of antiviral defense and tissue residency markers, anatomic locations, and TCR repertoires that target anatomically relevant viral antigens. Optimization of the location, number, and function of FRT TRMs is an important approach for improving host defenses to STIs.

Citing Articles

Tissue-Resident Memory CD8+ T Cells: Differentiation, Phenotypic Heterogeneity, Biological Function, Disease, and Therapy.

Xu L, Ye L, Huang Q MedComm (2020). 2025; 6(3):e70132.

PMID: 40066223 PMC: 11892159. DOI: 10.1002/mco2.70132.

Tissue-resident memory T-cell expressions and their prognostic role in head and neck squamous cell carcinoma: a systematic review and meta-analysis.

Ali A, Bari M, Arshad S, Wahid M, Safdar J, Anwar K BMC Cancer. 2025; 25(1):356.

PMID: 40011911 PMC: 11863602. DOI: 10.1186/s12885-025-13764-2.

Tissue-resident memory T cells in diseases and therapeutic strategies.

Xie D, Lu G, Mai G, Guo Q, Xu G MedComm (2020). 2025; 6(1):e70053.

PMID: 39802636 PMC: 11725047. DOI: 10.1002/mco2.70053.

Spatial transcriptomics unveils estrogen-modulated immune responses and structural alterations in the ectocervical mucosa of depot medroxyprogesterone acetate users.

Kaldhusdal V, Boger M, Tjernlund A, Burgener A, Bradley F, Lajoie J Sci Rep. 2025; 15(1):1014.

PMID: 39762272 PMC: 11704007. DOI: 10.1038/s41598-024-83775-9.

Spatial transcriptomics and immune cell profiling of the host ectocervical landscape of HIV infected Kenyan sex working women.

Boger M, Kaldhusdal V, Pascual-Reguant A, Kroh S, Uecker R, Burgener A Front Immunol. 2024; 15:1483346.

PMID: 39687623 PMC: 11646855. DOI: 10.3389/fimmu.2024.1483346.

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