CCR5 Expression is elevated on endocervical CD4+ T cells in healthy postmenopausal women

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 with 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: 3176) than premenopausal women (median: 1776; P = 0.02). Age and percent CCR5+CD4+ and CCR5+DR+38+CD4+ cells were linearly related in cervix (r ² = 0.47, P < 0.001 and r ² = 0.25, P = 0.01, respectively) and blood (r ² = 0.20, P = 0.001 and r ² = 0.31, P , 0.001; respectively), 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 omen, and if it is related to hormonal or nonhormonal effects of aging.