Cellular responses to interferon-gamma.
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.
Boehm
U
U
Institute for Genetics, University of Cologne, Köln, Germany. UBOEHM@GENETIK.UNI-KOELN.DE
Klamp
T
T
Groot
M
M
Howard
J C
JC
D000818:Animals; D017951:Antigen Presentation; D000998:Antiviral Agents / Q000378:metabolism; D017209:Apoptosis; D005786:Gene Expression Regulation; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D016897:Respiratory Burst; D015398:Signal Transduction; D014364:Tryptophan / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000998:Antiviral Agents; D007370:Interferon Type I; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D014364:Tryptophan