title: Ex vivo analysis of HIV-1 co-receptors at the endocervical mucosa of women using oral contraceptives.
abstract: Combined oral contraceptives may alter the microenvironment of the female genital tract and, thus, influence susceptibility of endocervical cells to HIV-1 transmission. The mechanism for this effect is unknown but might involve combined oral contraceptive up-regulation of chemokine receptors on CD4+ endocervical cells. We measured chemokine co-receptor (CCR5 and CXCR4) expression on cervical intraepithelial CD4+ T lymphocytes, macrophages and dendritic cells using flow cytometry in 32 healthy women, 16 of whom were combined oral contraceptive users and 16 non-users. All women tested negative for sexually transmitted infections. Combined oral contraceptive users showed a higher proportion of CCR5+ CD4+ T lymphocytes compared with combined oral contraceptive non-users (P < 0.05). However, expression of both co-receptors on cervical intraepithelial macrophages and dendritic cells was no different between the two groups. Up-regulation of CCR5 on cervical intraepithelial CD4+ T lymphocytes offers a potential explanation by which women receiving combined oral contraceptives may be at increased risk of HIV transmission.
authors.affiliation: Department of GU/HIV Medicine, Imperial College of Science, Technology and Medicine, Northwick Park Hospital, Harrow, Middlesex, UK.
authors.forename: Manyu
authors.initials: M
authors.lastname: Prakash
authors.forename: Steve
authors.initials: S
authors.lastname: Patterson
authors.forename: Frances
authors.initials: F
authors.lastname: Gotch
authors.forename: Moses S
authors.initials: MS
authors.lastname: Kapembwa
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002584:Cervix Uteri / Q000187:drug effects / Q000378:metabolism*; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009092:Mucous Membrane / Q000378:metabolism; D019713:Receptors, CCR5 / Q000187:drug effects / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000187:drug effects / Q000378:metabolism*
chemical_list: D003277:Contraceptives, Oral, Combined; D019713:Receptors, CCR5; D019718:Receptors, CXCR4