HIV-1 INDUCES CYTOTOXIC T-LYMPHOCYTES IN THE CERVIX OF INFECTED WOMEN

Although T lymphocytes are present in the genital mucosa, their functi on in sexually transmitted diseases is unproven. To determine if cervi cal T cells mediate HIV-specific cytolysis, mononuclear cells in cytob rush specimens from HIV-1-infected women were stimulated in vitro with antigen. Resultant cell lines lysed autologous targets expressing HIV -1 proteins in 12/19 (63%) subjects, and these responses were detected intermittently on repeated visits. All 8 subjects with blood CD4(+) c ounts greater than or equal to 500 cells/mu l had HIV-1-specific cervi cal CTL, whereas only 4/11 with counts <500 cells/mu l had detectable responses (P=0.008). Class II MHC-restricted CD4(+) CTL clones lysed t argets expressing EnV gp41 or infected with HIV-1. Class I MHC-restric ted CD8(+) clones recognized HIV-1 Gag- or Pol-expressing targets, and the epitopes were mapped to within 9-20 amino acids. Comparisons of i ntra-individual cervical and blood CTL specificities indicate that epi topes recognized by CTL in the cervix were commonly recognized in the blood. These studies provide the first definitive evidence for an MHC- restricted effector function in human cervical lymphocytes.