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

J Immunol. 1998 Jun 15;160(12):6032-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Cytokines
  • Interferon-alpha
  • Interleukin-18
  • RNA, Messenger
  • Interferon-beta
  • Interferon-gamma