[Interferon-gamma, the Th1/Th2 paradigm and autoimmune diseases].
Autoimmune diseases originate from a rupture in physiological immune tolerance towards self antigens. However, the formation of autoantibodies and autoreactive inflammatory cells is also regulated by the cytokine network, in which interferon-gamma (IFN-gamma), produced by NK and T lymphocytes, occupies a central position. IFN-gamma influences the function of all cell types involved in immune-mediated inflammatory reactions: antigen-presenting cells, cytotoxic and regulatory T lymphocytes, antibody-producing B lymphocytes, endothelial cells and mononuclear phagocytes. Experimental manipulations which affect the production or action of IFN-gamma invariably affect the course of experimentally induced autoimmune diseases in animals, but do so in divergent directions. A current explanatory framework for these actions of IFN-gamma invokes the T helper-1/T helper-2 (Th1/Th2) concept. According to this concept, autoimmune diseases, like other immune reactions, fall apart in two categories depending on whether the T helper lymphocytes assume a Th1 or Th2 profile. IFN-gamma is assumed to fulfill the function of a promotor and effector of the Th1 profile and is associated with inflammation and tissue damage typical for cell-mediated hypersensitivity reactions. Accordingly, IFN-gamma should boost autoimmune diseases of the Th1 type. However, experimental testing of this prediction contradicts this implication and necessitates revision of the function assigned to IFN-gamma in the Th1/Th2 concept.
Billiau
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Rega Instituut, Faculteit Geneeskunde-K.U.-Leuven.
D001327:Autoimmune Diseases / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000276:immunology*; D018448:Models, Immunological; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D007371:Interferon-gamma