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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1456652

Differential expression of HIV Target cells CCR5 and a4b7 in Tissue Resident Memory CD4 T cells in endocervix during the menstrual cycle of HIV seronegative women

Provisionally accepted
Sakthivel Govindaraj Sakthivel Govindaraj 1Staple Tyree Staple Tyree 2Gina B. Herring Gina B. Herring 3Sadia J. Rahman Sadia J. Rahman 1Hemalatha Babu Hemalatha Babu 1Chris Ibegbu Chris Ibegbu 1Marisa R. Young Marisa R. Young 2C C. Mehta C C. Mehta 4Lisa Haddad Lisa Haddad 5Alicia K. Smith Alicia K. Smith 2*Vijayakumar Velu Vijayakumar Velu 1*
  • 1 Emory National Primate Research Center, Emory University, Atlanta, Georgia, United States
  • 2 Department of Gynecology and Obstetrics, School of Medicine, Emory University, Atlanta, Georgia, United States
  • 3 Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States
  • 4 Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Colorado, United States
  • 5 Center for Biomedical Research, Population Council, New York, New York, United States

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

    Background: Ovarian hormones are known to modulate the immune system in the female genital tract (FGT). We sought to define the impact of the menstrual cycle on the mucosal HIV target cell levels, and tissue-resident CD4 T cells.Here, we characterized the distribution, phenotype, and function of CD4 T cells with special emphasis on HIV target cells (CCR5+ and α4β7+) as well as tissue-resident memory (TRM; CD69+ and CD103+) CD4 T cells in FGT of cycling women. Peripheral blood and Endocervical cells (EC-collected from cytobrush) were collected from 105 healthy women and performed multicolor flow cytometry to characterize the various subsets of CD4 T cells. Cervical vaginal lavage (CVL) were collected for cytokine analysis and plasma were collected for hormonal analysis. All parameters were compared between follicular and luteal phase of menstrual cycle.Our findings revealed no significant difference in the blood CD4 T cell subsets between the follicular and the luteal phase. However, in EC, the proportion of several cell types was higher in the follicular phase compared to the luteal phase of menstrual cycle, including CCR5+α4β7-cells (p=0.01), CD69+CD103+ TRM (p=0.02), CCR5+CD69+CD103+ TRM (p=0.001) and FoxP3+ CD4 T cells (p=0.0005). In contrast, α4β7+ CCR5-cells were higher in the luteal phase (p=0.0004) compared to the follicular phase. In addition, we also found that hormonal levels (P4/E2 ratio) and Th2 cytokines (IL-5 and IL-6) were with CCR5+ CD4 T cells subsets during the follicular phase of the menstrual cycle Conclusion: Overall, these findings suggest the difference in the expression of CCR5 and α4β7 in TRM CD4 T cell subsets in endocervix of HIV seronegative women between the follicular and luteal phase. Increase in the CCR5+ expression on TRM subsets could increase susceptibility to HIV infection during follicular phase of the menstrual cycle.

    Keywords: HIV target cells, HIV susceptibility, TRM, Menstrual cycle phase, endocervix

    Received: 28 Jun 2024; Accepted: 03 Sep 2024.

    Copyright: © 2024 Govindaraj, Tyree, Herring, Rahman, Babu, Ibegbu, Young, Mehta, Haddad, Smith and Velu. 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:
    Alicia K. Smith, Department of Gynecology and Obstetrics, School of Medicine, Emory University, Atlanta, GA 30322, Georgia, United States
    Vijayakumar Velu, Emory National Primate Research Center, Emory University, Atlanta, GA 30322, Georgia, United States

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