title: Peripheral blood monocytes derived from HIV+ individuals mediate antibody-dependent cellular cytotoxicity (ADCC).
abstract: Monocytes/macrophages serve a number of immunologic functions and play a major role in the host defense against infection. Abnormal functions of monocytes have been reported in AIDS and HIV+ individuals. A recent report from our laboratory demonstrated that peripheral blood monocytes (PBM) derived from AIDS patients were de novo "activated" as assessed by direct cell-mediated cytotoxicity (CMC) and secretion of cytotoxic factors and tumor necrosis factor-alpha (TNF alpha). Thus, both the direct cytotoxicity as well as the antibody-dependent cellular cytotoxicity (ADCC) exerted by the monocytes may contribute to the destruction of HIV-infected/coated cells and the immunopathogenesis of AIDS. The present study investigated the ability of HIV+ PBM to mediate ADCC against antibody-coated target cells in an 18-hr 51Cr release assay. Initial studies examined ADCC using a macrophage resistant target Raji and rabbit anti-Raji serum. The results show that the majority of PBM from HIV+ individuals mediate ADCC activity while the majority of PBM from normal healthy controls was not cytotoxic. While activation of PBM with recombinant interferon-gamma (rIFN-gamma) enhances the ADCC activity of normal PBM, treatment of HIV+ PBM with IFN-gamma resulted in significant enhancement of ADCC. Both untreated and treated PBM from HIV+ individuals had significantly higher ADCC than PBM from normal individuals. Of interest, a significant ADCC activity was found by PBM derived from two HIV- high risk individuals whether untreated or treated with rIFN-gamma. The ADCC results with RAJI target cells prompted us to investigate whether ADCC can also be obtained using HIV-infected T4+ cells. We selected a macrophage and TNF resistant T4+ CEM cell line as target for ADCC. The target was coated with inactivated HIV and pooled human anti-HIV serum was used. Studies with a few HIV+ individuals demonstrate that significant ADCC is obtained with PBM from HIV+ individuals but little or no ADCC by normal PBM and the ADCC was specific for HIV. The ADCC was also significantly enhanced by treatment of PBM with rIFN-gamma. The results of this study clearly indicate that PBM from HIV+ individuals are endowed with the capacity to mediate ADCC against HIV-infected/coated cells and thus, we postulate that PBM may play a direct role in vivo in lysis or suppression of HIV-coated/infected cells and in the pathogenesis of AIDS.
authors.affiliation: Department of Microbiology and Immunology, UCLA School of Medicine.
authors.forename: A
authors.initials: A
authors.lastname: Jewett
authors.forename: B
authors.initials: B
authors.lastname: Bonavida
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D002478:Cells, Cultured; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma