Changes to the cytokine microenvironment in the genital tract mucosa of HIV+ women.
As previous studies have indicated that genital tract mucosal T cell function may be impaired in HIV infection, we investigated the T cell cytokine mRNA in the genital tract mucosa of HIV-infected women to determine if there are alterations in the cytokine profile which may explain the T cell impairment. The in situ hybridization technique was used to investigate the T helper-1 (Th1: IL-2, interferon-gamma (IFN-gamma)) and Th2 cytokine (IL-4, IL-5, IL-10) mRNA profile in cervical biopsies from 10 HIV+ and 10 HIV- subjects. Cervical intraepithelial neoplasia (CIN) and genital infection had previously been excluded and the distribution of immunocompetent cells within the cervical mucosa was known for each subject. Non-parametric tests were used to compare the optical density (OD) of cytokine mRNA in the HIV+ and HIV- groups. Comparisons were also made between peripheral CD4 lymphocyte counts, cervical CD4/CD8 T lymphocyte ratios and cytokine mRNA OD in HIV+ subjects. The HIV+ women had significantly higher mRNA OD for the Th2 cytokines IL-4, IL-5 and IL-10 than HIV women. There was also significantly lower IL-2 mRNA OD in the former group. HIV+ women had lower IFN-gamma mRNA than HIV- women, but the difference was not statistically significant. There was no correlation between cytokine mRNA OD and peripheral CD4 count or cervical CD4/CD8 ratio. The predominance of Th2 cytokines, which are immuno-inhibitory, in the cervical mucosa of HIV+ women may underlie the impaired cytotoxic potential observed in the CD8+ T lymphocytes and may contribute to the susceptibility of HIV-infected women to recurrent genital tract infections and cervical neoplasia.
Olaitan
A
A
Department of Obstetrics and Gynaecology, The Royal Free Hospital and School of Medicine, London, UK.
Johnson
M A
MA
Reid
W M
WM
Poulter
L W
LW
D000328:Adult; D016207:Cytokines / Q000032:analysis / Q000276:immunology*; D005260:Female; D005836:Genitalia, Female / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D018928:Immunity, Mucosal; D017403:In Situ Hybridization; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D012333:RNA, Messenger