CHANGES TO THE CYTOKINE MICROENVIRONMENT IN THE GENITAL-TRACT MUCOSA OF HIV+ WOMEN

As previous studies have indicated that genital tract mucosal T cell f unction may be impaired in HIV infection, we investigated the T cell c ytokine mRNA in the genital tract mucosa of HIV-infected women to dete rmine if there are alterations in the cytokine profile which may expla in 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 biops ies from 10 HIV+ and 10 HIV- subjects. Cervical intraepithelial neopla sia (GIN) and genital infection had previously been excluded and the d istribution of immunocompetent cells within the cervical mucosa was kn own for each subject. Non-parametric tests were used to compare the op tical density (OD) of cytokine mRNA in the HIV+ and HIV- groups. Compa risons were also made between peripheral CD4 lymphocyte counts, cervic al 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 low er IL-2 mRNA OD in the former group. HIV+ women had lower IFN-gamma mR NA than HIV- women, but the difference was not statistically significa nt. There was no correlation between cytokine mRNA OD and peripheral C D4 count or cervical CD4/CD8 ratio. The predominance of Th2 cytokines, which are immune-inhibitory, in the cervical mucosa of HIV+ women may underlie the impaired cytotoxic potential observed in the CD8(+) T ly mphocytes and may contribute to the susceptibility of HIV-infected wom en to recurrent genital tract infections and cervical neoplasia.