BACKGROUND:The mucosal lymphocyte population is the largest in the body, and the gastrointestinal compartment has been well characterized in HIV infection. Much less is known about the effects of HIV on the genital tract. OBJECTIVE:: To examine the T-lymphocyte phenotype and receptor repertoire as well as total and virus-specific immunoglobulin concentrations in the endocervix of HIV-infected women at different stages of infection as compared with uninfected women. PATIENTS AND METHODS:Participants were 12 seronegative women, 10 HIV-infected "slow progressors" not taking antiretroviral therapy, and 9 HIV-infected women whose antiretroviral therapy was failing. We used multiparameter flow cytometry to enumerate T-cell populations on cytobrush-obtained cervical specimens, the immunoscope technique to determine the T-cell receptor (TCR) repertoire, and quantitative enzyme-linked immunosorbent assays for antibody determinations on cervical secretions absorbed onto ophthalmic sponges. Nonparametric statistical analyses were performed. RESULTS:We found marked depletion of leukocytes and CD4 T lymphocytes in the endocervix of HIV-infected women as compared with uninfected women; this was significant at more advanced disease stages. Naive T cells were rare in the endocervix of all groups. Activation marker expression was higher in endocervical T lymphocytes than in peripheral blood among control and slow-progressing HIV-infected women but not in women failing therapy. Endocervical T lymphocytes showed highly restricted utilization of Vbeta TCR families. Unlike other mucosal sites, the cervix contained IgG as the predominant immunoglobulin isotype. HIV-IgG was detected in the cervix of most HIV-infected women and in blood of all infected women. CONCLUSIONS:HIV infection induces substantial changes in the immune profile of the female genital tract. Further study of the implications of these findings for HIV acquisition and transmission is needed.