Ex vivo analysis of HIV-1 co-receptors at the endocervical mucosa of women using oral contraceptives.
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.
Prakash
Manyu
M
Department of GU/HIV Medicine, Imperial College of Science, Technology and Medicine, Northwick Park Hospital, Harrow, Middlesex, UK.
Patterson
Steve
S
Gotch
Frances
F
Kapembwa
Moses S
MS
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*
D003277:Contraceptives, Oral, Combined; D019713:Receptors, CCR5; D019718:Receptors, CXCR4