Cellular responses to interferon-gamma

Annu Rev Immunol. 1997;15:749-95. doi: 10.1146/annurev.immunol.15.1.749.

Abstract

Interferons are cytokines that play a complex and central role in the resistance of mammalian hosts to pathogens. Type I interferon (IFN-alpha and IFN-beta) is secreted by virus-infected cells. Immune, type II, or gamma-interferon (IFN-gamma) is secreted by thymus-derived (T) cells under certain conditions of activation and by natural killer (NK) cells. Although originally defined as an agent with direct antiviral activity, the properties of IFN-gamma include regulation of several aspects of the immune response, stimulation of bactericidal activity of phagocytes, stimulation of antigen presentation through class I and class II major histocompatibility complex (MHC) molecules, orchestration of leukocyte-endothelium interactions, effects on cell proliferation and apoptosis, as well as the stimulation and repression of a variety of genes whose functional significance remains obscure. The implementation of such a variety of effects by a single cytokine is achieved by complex patterns of cell-specific gene regulation: Several IFN-gamma-regulated genes are themselves components of transcription factors. The IFN-gamma response is itself regulated by interaction with responses to other cytokines including IFN-alpha/beta, TNF-alpha, and IL-4. Over 200 genes are now known to be regulated by IFN-gamma and they are listed in a World Wide Web document that accompanies this review. However, much of the cellular response to IFN-gamma can be described in terms of a set of integrated molecular programs underlying well-defined physiological systems, for example the induction of efficient antigen processing for MHC-mediated antigen presentation, which play clearly defined roles in pathogen resistance. A promising approach to the complexity of the IFN-gamma response is to extend the analysis of the less understood IFN-gamma-regulated genes in terms of molecular programs functional in pathogen resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigen Presentation
  • Antiviral Agents / metabolism
  • Apoptosis
  • Gene Expression Regulation
  • Humans
  • Interferon Type I / metabolism
  • Interferon-gamma / genetics
  • Interferon-gamma / physiology*
  • Models, Biological
  • Respiratory Burst
  • Signal Transduction
  • Tryptophan / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antiviral Agents
  • Interferon Type I
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Tryptophan