Oral contraceptive use induces upregulation of the CCR5 chemokine receptor on CD4(+) T cells in the cervical epithelium of healthy women.

Heterosexual transmission of human immunodeficiency virus type I (HIV-1) is the predominant mode of infection worldwide. Increased risk of HIV-1 transmission has been reported with oral contraceptive use. To elucidate the underlying mechanism of this observation, intraepithelial endocervical T lymphocytes from women using oral contraceptives were analysed for expression of activation and chemokine receptors. T lymphocytes from the cervical epithelium and peripheral blood of women using combined oral contraceptives (COC) and those using no contraceptive method (NONE) were compared. Cervical T lymphocytes were obtained with a cytobrush and in parallel, mononuclear leukocytes were separated from blood by centrifugation over a ficoll-hypaque gradient. Cellular activation markers and HIV-1 chemokine co-receptors, CXCR4 and CCR5, were analysed by flow cytometry. Activation markers (CD69, CD25 and HLA-DR) on T cells were expressed at higher levels in the cervical epithelium than peripheral blood T cells but were no different in those women using COC. CXCR4 was widely expressed on cervical and on blood T cells, but was not influenced by COC use. By contrast, the number of T cells expressing CCR5 increased in women using COC (P<0.05). The level of cervical CCR5 expression per cell was shown to increase on both activated CD4(+) (CD69(+), P<0.05; HLA-DR(+), P<0.01) and CD8(+) (CD69(+), P<0.05; HLA-DR(+), P<0.05) T lymphocytes compared with COC use. These data show that with COC use, the expression of CCR5 on CD4(+) T lymphocytes is increased. Furthermore, the cell surface density of CCR5 is increased on both CD4(+) and CD8(+) T lymphocyte subsets. These findings suggest a mechanism by which oral contraceptive use can increase the risk of HIV-1 transmission.