PMID- 2104787 OWN - NLM STAT- MEDLINE DCOM- 19900222 LR - 20190820 IS - 0090-1229 (Print) IS - 0090-1229 (Linking) VI - 54 IP - 2 DP - 1990 Feb TI - Peripheral blood monocytes derived from HIV+ individuals mediate antibody-dependent cellular cytotoxicity (ADCC). PG - 192-9 AB - 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. FAU - Jewett, A AU - Jewett A AD - Department of Microbiology and Immunology, UCLA School of Medicine. FAU - Bonavida, B AU - Bonavida B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Immunol Immunopathol JT - Clinical immunology and immunopathology JID - 0356637 RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Antibody-Dependent Cell Cytotoxicity/*immunology MH - Cells, Cultured MH - HIV/immunology MH - HIV Infections/*immunology MH - Humans MH - *Immunity, Cellular MH - In Vitro Techniques MH - Interferon-gamma/pharmacology MH - Monocytes/*immunology MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 1990/02/01 00:00 MHDA- 1990/02/01 00:01 CRDT- 1990/02/01 00:00 PHST- 1990/02/01 00:00 [pubmed] PHST- 1990/02/01 00:01 [medline] PHST- 1990/02/01 00:00 [entrez] AID - 10.1016/0090-1229(90)90081-z [doi] PST - ppublish SO - Clin Immunol Immunopathol. 1990 Feb;54(2):192-9. doi: 10.1016/0090-1229(90)90081-z.