The phytohemagglutinin-induced virus-inhibitor may, however, be produced in white cells in response to a stimulation of cellular RNA synthesis and may be a feedback mechanism for control of RNA synthesis. E. Frederick Wheelock (1965)

Interferons are cytokines that play a complex and central role in the resistance of mammalian hosts to pathogens. Type I interferon (IFN-α and IFN-β) is secreted by virus-infected cells. Immune, type II, or γ-interferon (IFN-γ) 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-γ 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-γ-regulated genes are themselves components of transcription factors. The IFN-γ response is itself regulated by interaction with responses to other cytokines including IFN-α/β, TNF-α, and IL-4. Over 200 genes are now known to be regulated by IFN-γ and they are listed in a World Wide Web document that accompanies this review. However, much of the cellular response to IFN-γ 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-γ response is to extend the analysis of the less understood IFN-γ-regulated genes in terms of molecular programs functional in pathogen resistance.