title: Dual role of TNF-alpha in NK/LAK cell-mediated lysis of chronically HIV-infected U1 cells. Concomitant enhancement of HIV expression and sensitization of cell-mediated lysis.
abstract: The U937-derived chronically HIV-infected U1 cell line and uninfected U937 cell clones were efficiently lysed by both unstimulated (NK) and IL-2-stimulated (lymphokine-activated killer; LAK) peripheral blood mononuclear cells (PBMC) of healthy HIV-seronegative donors. Pretreatment of target cells with IFN-gamma down-modulated killing of both U1 cells and two U937 cell clones, and up-regulated MHC class I expression. In contrast, TNF-alpha enhanced the sensitivity of infected U1 cells, but not of U937 cell clones to NK / LAK cell lysis. Co-cultivation of IL-2-stimulated PBMC with U1 cells triggered expression and replication of HIV by cell-cell contact, and this effect was inhibited by anti-TNF-alpha antibodies (Ab); virus production was partially inhibited by zidovudine. Of interest, anti-TNF-alpha Ab protected U1 cells from LAK cell activity. Thus, TNF-alpha can induce HIV expression from chronically infected U1 cells, but also plays an important role in sensitizing these cells to lysis.
authors.affiliation: Laboratory of Clinical Immunology, Division of Infectious Diseases, Centro San Luigi, San Raffaele Scientific Institute, Milano, Italy. fortis.claudio@hsr.it
authors.forename: C
authors.initials: C
authors.lastname: Fortis
authors.forename: P
authors.initials: P
authors.lastname: Biswas
authors.forename: L
authors.initials: L
authors.lastname: Soldini
authors.forename: F
authors.initials: F
authors.lastname: Veglia
authors.forename: A M
authors.initials: AM
authors.lastname: Careddu
authors.forename: F
authors.initials: F
authors.lastname: Delfanti
authors.forename: B
authors.initials: B
authors.lastname: Mantelli
authors.forename: M
authors.initials: M
authors.lastname: Murone
authors.forename: A
authors.initials: A
authors.lastname: Lazzarin
authors.forename: G
authors.initials: G
authors.lastname: Poli
mesh_terms: D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D054303:HIV Reverse Transcriptase / Q000096:biosynthesis; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D020298:U937 Cells
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D054303:HIV Reverse Transcriptase