Antibody dependent cell-mediated cytotoxicity against HIV-1 gp120 in mucosal secretions

Purpose: Low antibody dependent cell-mediated cytotoxicity (ADCC) titers in serum correlate with rapid progression in HIV+ men in the Multicenter AIDS Cohort Study (MACS). Studies of ADCC activity in women have been limited. Although IgG and sIgA are often abundant in cervical fluid of HIV+ women, functional ADCC titers have not been reported in mucosal secretions. The goal of these studies was to determine whether antibodies in mucosal secretions have ADCC activity. Methods: We evaluated cervical lavage fluids (CVL) and paired sera from participants in the Women's Interagency HIV Study. Normal PBL were incubated with patient's serum and ⁵¹Cr-labeled gp120 coupled CEM.NKR to determine the titer of antibodies with ADCC activity against HIV. Results: 43% had serum ADCC activity 3 standard deviations above the mean of 16 HIV-women. ADCC activity in HIV+ women with a CD4 cell number greater than 500 cells/ul was not as high as previously seen in long term survivors from the MACS. 22% of the HIV+ women had CVL ADCC activity. Most had either serum or CVL activity but not both. 60% of the women evaluated had either CVL or serum ADCC activity against HIV gp120. Conclusions: ADCC antibodies are present in CVL. Since levels do not correlate with serum ADCC, they may be produced locally. Clinical Implications: ADCC activity is present in vaginal secretions of HIV+ women and may also be present in other mucosal secretions including those of the gut or lung.