Phenotype and Functionality of CD4⁺ and CD8⁺ T Cells in the Upper Reproductive Tract of Healthy Premenopausal Women

Abstract

Problem The goal of this study was to investigate the phenotype and functional responsiveness of CD4+ and CD8+ T-cells in the upper reproductive tract of healthy premenopausal women. The lower reproductive tract is frequently studied as a site of sexually transmitted infections; however, the upper tract may also be a portal of entry and dissemination for pathogens, including HIV-1. Method of Study Endometrial biopsy, endocervical curettage, cytobrush and blood were collected during mid-luteal phase from 23 healthy women. T-cells were isolated and analyzed by flow cytometry. Results As compared to their counterparts in blood, endometrial and endocervical T-cells had enhanced CCR5 expression, and were enriched for activated, effector memory cells. Endometrial T-cells were more responsive to polyclonal stimuli, producing a broad range of cytokines and chemokines. Conclusions These findings underscore the responsiveness of endometrial T-cells to stimulation, and reveal their activated phenotype. These findings also suggest susceptibility of the upper reproductive tract to HIV-1 infection.

Immunologic, Virologic, and Pharmacologic Characterization of the Female Upper Genital Tract in HIV-Infected Women

“…Research related to the immunologic effect of HIV on the UGT is limited though the data available shows the endometrium in a chronic inflammatory state in HIV-infected women. 36–38 Enhanced immune activation in endometrial samples of HIV-negative women has previously been reported; 19 this is consistent with our findings that immune activation is high in the endometrium of both HIV-infected and HIV-negative women. These high levels of immune activation imply that there are target cells for HIV transmission, replication and shedding in the endometrium.…”

“…8–18 However, the uterine endometrium [upper genital tract (UGT)] contains activated CCR5+ T-cells, which are a target for HIV transmission. 19 It is plausible that the UGT could serve as site of HIV acquisition, replication, and viral shedding. 20–27 This feasibility study was conducted to better understand the biology of HIV in the UGT.…”

The Role of Sex Hormones and the Tissue Environment in Immune Protection Against HIV in the Female Reproductive Tract

“…Additionally, there is an inverse CD4/CD8 ratio 13, 55, 56 . Using endometrial biopsies, Shanmugasundaram et al 3 demonstrated that CD4 + and CD8 + T cells in the endometrium are mostly of the effector memory phenotype (T EM ) and express higher levels of CD38 and HLA-DR than cells in peripheral blood, indicating a more activated state. NK cells are far more abundant in the endometrium than in blood and are characterized by high expression of CD56 and lack of CD16 57, 58 , which represents an immunomodulatory subset of NK cells 59 .…”

“…The mucosal immune system in the FRT contains a spectrum of immune cells including NK cells, neutrophils, macrophages and T cells that are different from their blood counterparts al 3,4,52, 53 . In addition to their unique phenotypic characteristics, these cells are functionally unique and responsive to changes in hormone balance during the menstrual cycle 5 .…”

Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection

“…59 Other studies have also examined the proportions and localization of T-cell populations in the cervix and vagina of nonpregnant women. Pudney et al 46 performed an extensive immunohistological characterization to show that the T cells were the most prevalent in the cervical transformation zone and surrounding tissue, whereas the vaginal tissue contained few T cells.…”