Increased Cervical CD4+CCR5+ T Cells Among Kenyan Sex Working Women Using Depot Medroxyprogesterone Acetate.

Depot medroxyprogesterone acetate (DMPA) is the most common hormonal contraceptive used by women in sub-Saharan Africa, however, it has been epidemiologically associated with HIV infections. To assess whether DMPA has an effect on the number and activation of HIV target cells, this study assessed the levels and phenotype of blood- and mucosal-derived HIV target cells among women using DMPA. Thirty-five HIV uninfected women from the Pumwani Sex Worker cohort from Nairobi, Kenya were enrolled in the study (15 using DMPA and 20 not using hormonal contraception). Blood (plasma and peripheral blood mononuclear cells) and cervicovaginal (lavage, cervical cells, and ectocervical biopsies) samples were collected. Cellular phenotype and activation status were determined by flow cytometry, cytokine levels were assessed by bead array and image analysis assessed cell number and phenotype in situ. In blood, the proportion of HIV target cells and activated T cells was lower in DMPA users versus those not using hormonal contraceptives. However, analysis of cervical mononuclear cells showed that DMPA users had elevated levels of activated T cells (CD4+CD69+) and expressed lower levels of the HIV co-receptor CCR5 on a per cell basis, while tissue samples showed that in the ectocervix, DMPA users had a higher proportion of CD4+CCR5+ T cells. This study demonstrates that DMPA users had higher levels of activated T cells and HIV target cells in the genital tract. The increased pool of mucosal HIV target cells provides new biological information about the potential impact of DMPA on HIV susceptibility.

CD161 identifies polyfunctional Th1/Th17 cells in the genital mucosa that are depleted in HIV-infected female sex workers from Nairobi, Kenya.

CD161 identifies a subset of circulating Th17 cells that are depleted in the blood and gut of HIV-infected individuals. In the female reproductive tract (FRT), the pattern of CD161 expression on CD4+ cells remains unknown. Here, we characterized CD161 expression in the FRT of Kenyan female sex workers (FSW). Compared to the blood, CD161+CD4+ T cells were enriched in the FRT of uninfected FSWs. These cells were depleted in FRT of HIV-infected FSWs. Cervical CD161+ cells harboured an activated phenotype (CD69, CD95, HLA-DR) with elevated expression of tissue-homing markers (CCR6, ß7 integrin) and HIV co-receptor (CCR5). Mitogen-stimulated production of IL-17 confirmed the Th17 commitment of CD161+CD4+ T cells in the FRT with a predominance of polyfunctional Th1/Th17 cells. Here, we showed that the expression of CD161 on CD4+T cells is modulated at the FRT, but still identified a highly activated cellular subset, which differentiates into pro-inflammatory Th1/Th17 cells, expresses multiple HIV susceptibility markers and are depleted in HIV-infected individuals. The use of CD161 as a biomarker of HIV targets in the FRT reduces the need for functional assessment of cells and could have important implications in better understanding HIV pathogenesis and Th17 fate in the FRT of high-risk women.

The Impact of Sex Work Interruption on Blood-Derived T Cells in Sex Workers from Nairobi, Kenya.

BACKGROUND: Unprotected sexual intercourse exposes the female genital tract (FGT) to semen-derived antigens, which leads to a proinflammatory response. Studies have shown that this postcoital inflammatory response can lead to recruitment of activated T cells to the FGT, thereby increasing risk of HIV infection. OBJECTIVE: The purpose of this study was to evaluate the impact of sex work on activation and memory phenotypes of peripheral T cells among female sex workers (FSW) from Nairobi, Kenya. SUBJECTS: Thirty FSW were recruited from the Pumwani Sex Workers Cohort, 10 in each of the following groups: HIV-exposed seronegative (at least 7 years in active sex work), HIV positive, and New Negative (HIV negative, less than 3 years in active sex work). Blood was obtained at three different phases (active sex work, abstinence from sex work-sex break, and following resumption of sex work). Peripheral blood mononuclear cells were isolated and stained for phenotypic markers (CD3, CD4, CD8, and CD161), memory phenotype markers (CD45RA and CCR7), activation markers (CD69, HLA-DR, and CD95), and the HIV coreceptor (CCR5). T-cell populations were compared between groups. RESULTS: In HIV-positive women, CD8+CCR5+ T cells declined at the sex break period, while CD4+CD161+ T cells increased when returning to sex work. All groups showed no significant changes in systemic T-cell activation markers following the interruption of sex work, however, significant reductions in naive CD8+ T cells were noted. For each of the study points, HIV positives had higher effector memory and CD8+CD95+ T cells and lower naive CD8+ T cells than the HIV-uninfected groups. CONCLUSIONS: Interruption of sex work had subtle effects on systemic T-cell memory phenotypes.