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The CySF-L2 factor from dialysable human leucocyte extract activates natural killer cytotoxicity by induction of interferon γ

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Summary

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 γ (IFNγ) release was the crucial step during CySF-L2-mediated NK cytotoxicity activation since enhancement of NK activity was completely blocked when anti-IFNγ antibodies were present during treatment of PBMC. Anti-IFNα, anti-TNFα (tumour necrosis factor α) 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 IFNγ from CD3+T cells and CD56+CD3− NK cells and of TNFα 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.

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  1. Friedrich-Miescher-Laboratorium, Max-Planck-Gesellschaft, Spemannstrasse 37/39, D-7400, Tübingen, Germany

    Ingeborg Doelker & F. Alfred Anderer

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  1. Ingeborg Doelker
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  2. F. Alfred Anderer
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Doelker, I., Anderer, F.A. The CySF-L2 factor from dialysable human leucocyte extract activates natural killer cytotoxicity by induction of interferon γ. Cancer Immunol Immunother 34, 299–305 (1992). https://doi.org/10.1007/BF01741550

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  • DOI: https://doi.org/10.1007/BF01741550

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