title: The CySF-L2 factor from dialysable human leucocyte extract activates natural killer cytotoxicity by induction of interferon gamma.
abstract: The mechanism of natural killer (NK) cytotoxicity activation of human peripheral blood mononuclear cells (PBMC) by CySF-L2 was elucidated. CySF-L2 is a cytotoxicity-stimulating factor isolated from dialysable human leucocyte extract, which activates NK cytotoxicity against NK-sensitive and insensitive tumour cells (K562; Daudi; Raji; MOLT4) when preincubated with effector cells for 72 h. CySF-L2-mediated activation was synergistic to interleukin-2(IL-2)-mediated activation of NK cytotoxicity. Induction of interferon gamma (IFN gamma) release was the crucial step during CySF-L2-mediated NK cytotoxicity activation since enhancement of NK activity was completely blocked when anti-IFN gamma antibodies were present during treatment of PBMC. Anti-IFN alpha, anti-TNF alpha (tumour necrosis factor alpha) anti-IL-1 and anti-IL-2 antibodies showed no blocking effect. Analysis of the supernatant culture medium after 72 h incubation of PBMC and their highly purified subpopulations demonstrated that CySF-L2 induced release of IFN gamma from CD3+T cells and CD56+CD3- NK cells and of TNF alpha and prostaglandin E2 from monocytes. CySF-L2 was also capable of activating NK cytotoxicity of highly purified (98%) CD56+CD3- NK cells as well as of monocytes (94% pure). Cell cooperation studies connected with analysis of cytokine release and enhancement of NK cytotoxicity indicated that CySF-L2 might play an essential role in the up and down regulation of NK cytotoxicity by the cytokine network.
authors.affiliation: Friedrich-Miescher-Laboratorium, Max-Planck-Gesellschaft, Tübingen, Federal Republic of Germany.
authors.forename: I
authors.initials: I
authors.lastname: Doelker
authors.forename: F A
authors.initials: FA
authors.lastname: Anderer
mesh_terms: D000954:Antigens, Surface / Q000276:immunology; D003956:Dialysis; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014020:Tissue Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D007376:Interleukin-2; D014020:Tissue Extracts; D014409:Tumor Necrosis Factor-alpha; C052730:lymphokine-activated cell-associated antigen; D007371:Interferon-gamma; D015232:Dinoprostone