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Article: Influenza A virus-induced IFN-alpha/beta and IL-18 synergistically enhance IFN-gamma gene expression in human T cells.

Sareneva, T / Matikainen, S / Kurimoto, M / Julkunen, I

Journal of immunology (Baltimore, Md. : 1950)

1998  Volume 160, Issue 12, Page(s) 6032–6038

Abstract: ... synthesis in human T cells. Influenza A virus-infected human peripheral macrophages secreted IFN-alpha/beta ... gene expression and protein production. The data suggest that IFN-alpha/beta and IL-18 produced by macrophages ... in T cells independently of protein synthesis. IL-18 synergized with IFN-alpha to up-regulate IFN-gamma ...

Abstract T cells contribute significantly the to host's early defense against viral and bacterial infections and are essential for clearance of the pathogen. IFN-gamma, a product of activated T and NK cells, has, in addition to its direct antimicrobial activity, a major role in activating cell-mediated immunity. Here we report that cytokines secreted by influenza A virus-infected macrophages are able to induce IFN-gamma synthesis in human T cells. Influenza A virus-infected human peripheral macrophages secreted IFN-alpha/beta, TNF-alpha, IL-1beta, and a recently identified cytokine, IL-18 (or IFN-gamma-inducing factor), whereas the production of IL-12 was not detected. Supernatants collected from virus-infected macrophages induced rapid IFN-gamma mRNA expression and protein production in T cells. This was down-regulated by the addition of neutralizing anti-IFN-alpha/beta Abs, whereas neutralizing anti-IL-12 Abs had no effect on IFN-gamma gene expression. Exogenously added IFN-alpha/beta also rapidly stimulated the synthesis of IFN-gamma mRNA in T cells independently of protein synthesis. IL-18 synergized with IFN-alpha to up-regulate IFN-gamma gene expression and protein production. The data suggest that IFN-alpha/beta and IL-18 produced by macrophages during virus infection may act together to induce IFN-gamma synthesis and, consequently, may play an important role for both of these cytokines in the development of Th1-type immune responses.
MeSH term(s) Cytokines/biosynthesis ; Gene Expression Regulation ; Humans ; Influenza A virus ; Influenza, Human/immunology ; Interferon-alpha/biosynthesis ; Interferon-beta/biosynthesis ; Interferon-gamma/biosynthesis ; Interferon-gamma/genetics ; Interleukin-18 ; Macrophages/immunology ; Macrophages/virology ; RNA, Messenger/metabolism ; T-Lymphocytes/metabolism ; Th1 Cells/immunology ; Th1 Cells/virology
Chemical Substances Cytokines ; Interferon-alpha ; Interleukin-18 ; RNA, Messenger ; Interferon-beta (77238-31-4) ; Interferon-gamma (82115-62-6)
Language English
Publishing date 1998-06-15
Publishing country United States
Document type Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID 3056-9
ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online) 1550-6606
ISSN 0022-1767 ; 1048-3233 ; 1047-7381
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