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Immunological Microenvironments in the Human Vagina and Cervix: Mediators of Cellular Immunity Are Concentrated in the Cervical Transformation Zone¹

From the Fearing Research Laboratory, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

ABSTRACT

Cell-mediated immunity (CMI) is key to defense against intracellular pathogens such as Chlamydia trachomatis and viruses that infect the lower female genital tract, but little is known about CMI at this site. Recent studies indicate that there are immunological microenvironments within the female genital tract, and that immune functions are affected by hormones as well as infections and inflammatory processes. To determine the distribution of mediators of CMI within the lower female genital tract, we have enumerated and characterized T-lymphocyte subsets and natural killer and antigen presenting cells (APCs; macrophages and dendritic cells) in the introitus, vagina, ectocervix, endocervix and cervical transformation zone (TZ) from healthy women, and have examined the effects of the menstrual cycle, menopause and inflammation on these parameters. In women without inflammation, T cells and APCs were most prevalent in the cervical TZ and surrounding tissue. Intraepithelial lymphocytes were predominantly CD8+ T cell+; most CD8+ cells in the TZ and endocervix, and a proportion of cells in the ectocervix, expressed T-cell internal antigen-1, a marker of cytotoxic potential. In contrast, the normal vaginal mucosa contained few T cells and APCs. Cervicitis and vaginitis cases had increased numbers of intraepithelial CD8+ and CD4+ lymphocytes and APCs. The menstrual cycle and menopause had no apparent effect on cellular localization or abundance in any of the lower genital tract tissues. These data indicate that the cervix, especially the TZ, is the major inductive and effector site for CMI in the lower female genital tract. Because CD4+ T cells and APCs are primary host cells for human immunodeficiency virus type 1 (HIV-1), these data also provide further evidence that the cervix is a primary infection site of HIV-1, and that inflammation increases the risk of HIV transmission.

cervix, female reproductive tract, menstrual cycle, vagina

¹ Supported in part by NIH grant R01HD33205 and by contract CSA-88–020 from the Contraceptive Research and Development Program (CONRAD) under a cooperative agreement with the United States Agency for International Development (USAID), which in turn receives funds for AIDS research from an interagency agreement with the National Institutes of Child Health and Human Development. The views expressed by the authors do not necessarily reflect the views of USAID or CONRAD.

² Correspondence. FAX: 617 414 8481; jeffrey.pudney{at}bmc.org

³ Current address: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Boston University School of Medicine, 715 Albany St.-Evans 230, Boston, MA 02118.

⁴ Current address: Department of Microbiology, Immunology, and Parasitology, LSU Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112-1393.

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