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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Mucosal Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1465124

Impact of aging on the frequency, phenotype, and function of CD4+ T cells in the human female reproductive tract

Provisionally accepted
Zheng Shen Zheng Shen 1*Landon G. vom Steeg Landon G. vom Steeg 1Mickey V. Patel Mickey V. Patel 1Marta Rodriguez-Garcia Marta Rodriguez-Garcia 2,3Charles R. Wira Charles R. Wira 1
  • 1 Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire, United States
  • 2 Department of Biochemistry, Microbiology & Immunology, School of Medicine, Wayne State University, Detroit, Michigan, United States
  • 3 C.S. Mott Center for Human Growth and Development, School of Medicine, Wayne State University, Detroit, Michigan, United States

The final, formatted version of the article will be published soon.

    Since CD4+ T cells are essential for regulating adaptive immune responses and for long lasting mucosal protection, changes in CD4+ T cell numbers and function are likely to affect protective immunity. What remains unclear is whether CD4+ T cell composition and function in the female reproductive tract (FRT) changes as women age. Here we investigated the changes in the composition and function of CD4+ T cells in the endometrium (EM), endocervix (CX), and ectocervix (ECX) with aging. We observed a significant decrease in both the total number and percentage of CD4+ T cells in the EM with increasing age, particularly in the years following menopause. CD4+ T cells within the FRT predominantly expressed CD69. The proportion of CD69+CD4+ T cells increased significantly with increasing age in the EM, CX and ECX. The composition of T helper cell subsets within the EM CD4+ T cell population also showed age-related changes. Specifically, there was a significant increase in the proportion of Th1 cells and a significant decrease in Th17 and Treg cells with increasing age. Furthermore, the production of IFNγ by CD4+ T cells in the EM, CX, and ECX significantly decreased with increasing age upon activation. Our findings highlight the complex changes occurring in CD4+ T cell frequency, phenotype, and function within the FRT as women age. Understanding these age-related immune changes in the FRT is crucial for enhancing our knowledge of reproductive health and immune responses in women.

    Keywords: Aging, Menopause, Human female reproductive tract, CD4+ T cells, tissue resident memory phenotypeT cells, cytokine production

    Received: 15 Jul 2024; Accepted: 27 Aug 2024.

    Copyright: © 2024 Shen, vom Steeg, Patel, Rodriguez-Garcia and Wira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zheng Shen, Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Lebanon, 03756, New Hampshire, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.