Increase in Endocervical CD4 Lymphocytes among Women with Nonulcerative Sexually Transmitted Diseases

Abstract

To assess associations of nonulcerative sexually transmitted diseases (STDs) with human immunodeficiency virus (HIV)-susceptible leukocytes on female genital mucosa, cervicovaginal specimens from 32 HIV-negative STD clinic patients with gonorrhea, chlamydial infection, or trichomoniasis were compared with specimens from 32 clinic patients without these infections. Twenty-eight patients had single infections (15 gonorrhea, 10 chlamydial infection, 3 trichomoniasis), and 4 had dual infections. A saline vaginal wash and saline suspensions of vaginal wall scrapings, ectocervical scrapings, and endocervical brushings were analyzed by flow cytometry. Specimens from the endocervix had the highest proportions of lymphocytes, monocytes, and Langerhans' cells. The median number of endocervical CD4 lymphocytes/10,000 cells was greater among patients with STDs than among those without (476 vs. 245; P < .001). These data suggest that the endocervix may have a particularly important role in heterosexual HIV transmission and that nonulcerative STDs may facilitate HIV transmission by increasing the presence of CD4 lymphocytes at this site.

HIV‐1 co‐receptor expression and epithelial immune cells of the cervix in asymptomatic women attending a genitourinary medicine clinic

“…The presence of B cells has been taken by some to denote contamination by systemic blood [19]; however, our protocol aimed to disqualify any specimens presenting visible blood. It should be noted that others have found B lymphocytes in similar abundance, or even in excess of HIV-susceptible cells in previous genital tract studies [7].Our findings of parity between CCR5 and CXCR4 expression on all cellular denominations except for CD14 cells are in agreement with the findings of many studies [12,13,20,23] and at odds with others [11]. Discrepancy in the role of chemokine receptor expression in selective HIV transmission can largely be explained by variable anatomical sampling sites, methods of sampling and choice of assays and associated sensitivities in detection.…”

“…Indeed, characterization of the female genital epithelia has detailed HIV susceptibility of all tissue types (vagina, ectocervix, transformation zone and endocervix), by a range of mechanisms (receptor-mediated fusion, transcytosis, endocytosis, and direct breach of damaged epithelia) (reviewed in [5,6]). However, the cervical transformation zone and adjacent endocervical canal have been hypothesized as the focal point for immune cell presence and thus also de novo HIV entry [7,8].Data on chemokine expression on cervical immune cells are limited. Endocervical epithelial T-cell expression of CCR5 has been observed at a higher level than in peripheral blood [9], and others have observed marginally higher still cervical CXCR4 levels [10].…”

Anatomic and Hormonal Changes in the Female Reproductive Tract Immune Environment during the Life Cycle: Implications for HIV/STI Prevention Research

“…32 Other immunologic factors that may facilitate HIV infection, including CD4 positive Thelper cells and the expression of the chemokine receptor CCR5, are also found more frequently with columnar epithelium of the endocervical mucosa compared with the squamous epithelium of the ectocervix and vagina. [33][34][35][36] Increased cervical CCR5 expression in post-menopausal women may increase their risk for HIV-1 acquisition, and further studies are needed to understand whether increased CCR5 expression is related to hormonal effects of aging.…”

Vigorous Response of Human Innate Functioning IgM Memory B Cells upon Infection by Neisseria gonorrhoeae

“…gonorrhoeae has a curious niche, such that the pathogen seems to penetrate and persist within the subepithelial space (9); this site is rich in nutrients but also patrolled by resident sentinel immune cells (16,40) that the bacteria must contend with. Leukocytes, including B cells, accumulate in the endocervical mucosa during both symptomatic and asymptomatic gonococcal infections (16), This prevents T cell and B cell collaboration, abrogating the production of a T cell-dependent memory response.…”

“…In fact, clinical evidence enticingly suggests that gonococcal infection might directly influence the B cell response. There is an increase in both B and T lymphocytes in the endocervix of women with nonulcerative sexually transmitted infections including N. gonorrhoeae (16), suggesting that the bacteria may directly access the B cells. Ig production within the male and female genital tract is distinct from that of other mucosal surfaces in that IgG predominates rather than IgA (17).…”