CCR5 Expression Is Elevated on Endocervical CD4+ T Cells in Healthy Postmenopausal Women

Abstract

Background New HIV-1 infections are increasing in older American women largely through heterosexual transmission. Activated CD4+ T-cells and CCR5 expression are linked to HIV-1 susceptibility, but whether these parameters are altered in the cervix of older women is unknown. Methods Whole blood and in some instances endocervical brush samples were collected from healthy premenopausal (n=22) and postmenopausal women (n=24). Percentages of HLA-DR(DR)+CD38(38)+CD4+ T-cells, and HIV-1 chemokine coreceptor expression were determined by flow cytometry. Results Percentages of DR+38+CD4+ T-cells were 6-times greater in cervix (median, 6.4%) than blood (median, 1.1%; p<0.001), but did not differ within each compartment between premenopausal and postmenopausal women (p=0.2). Postmenopausal women had greater percentages of CCR5+CD4+ and CCR5+DR+38+CD4+ T-cells compared to premenopausal women in cervix (median, 70% vs. 42%, p=0.005; and 80% vs. 57%; p<0.05, respectively) and blood (medians, 22% vs. 13%, and 76% vs. 62%, respectively; p<0.001). Postmenopausal women had more CCR5 molecules on cervical DR+38+CD4+ T-cells (median, 3,176) than premenopausal women (median, 1,776; p=0.02). Age and percent CCR5+CD4+ and CCR5+DR+38+CD4+-cells were linearly related in cervix (r2=0.47, p<0.001 and r2=0.25, p=0.01, respectively) and blood (r2=0.20, p=0.001 and r2=0.31, respectively; p<0.001), but confounding of age with menopause could not be excluded. Cervical CXCR4 expression did not differ substantially between premenopausal and postmenopausal women. Conclusions Elevated cervical CCR5 expression in postmenopausal women may increase their risk for HIV-1 acquisition. Studies are needed to confirm whether elevated CCR5 expression confers increased HIV-1 susceptibility in postmenopausal women, and if it is related to hormonal or nonhormonal effects of aging.

Reduced levels of genital tract immune biomarkers in postmenopausal women: implications for HIV acquisition

“…[34,35]. It is possible that we did not observe this as we focused on the soluble immune mediators rather than the cellular components in the genital tract.…”

Research Gaps in Defining the Biological Link between HIV Risk and Hormonal Contraception

“…42 Increased CCR5 expression on endocervical CD4 + T cells was also reported in healthy post-menopausal women. 43 These data collectively suggest that increased expression of CCR5 may contribute to the epidemiological link between DMPA and HIV, but larger studies are needed to address the impact of HC on the number and function of mucosal and systemic immune cell populations.…”

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

“…Additionally, CCR5 expression may be regulated by the menopausal status, since cells from postmenopausal women expressed more CCR5 than premenopausal women 70 (Rodriguez-Garcia et al, unpublished data). Saba et al 15 found that about 50% of CD4 + T cells expressed HIV-coreceptor CCR5.…”