The role of IFN-gamma in systemic lupus erythematosus: a challenge to the Th1/Th2 paradigm in autoimmunity.
The classification of T helper cells into type 1 (Th1) and type 2 (Th2) led to the hypothesis that Th1 cells and their cytokines (interleukin [IL]-2, interferon [IFN]-gamma) are involved in cell-mediated autoimmune diseases, and that Th2 cells and their cytokines (IL-4, IL-5, IL-10, IL-13) are involved in autoantibody(humoral)-mediated autoimmune diseases. However, this paradigm has been refuted by recent studies in several induced and spontaneous mouse models of systemic lupus erythematosus, which showed that IFN-gamma is a major effector molecule in this disease. These and additional findings, reviewed here, suggest that these two cross-talking classes of cytokines can exert autoimmune disease-promoting or disease-inhibiting effects without predictability or strict adherence to the Th1-versus-Th2 dualism.
Theofilopoulos
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AN
The Scripps Research Institute, Department of Immunology/IMM3, La Jolla, CA 92037, USA. argyrio@scripps.edu
Koundouris
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S
Kono
D H
DH
Lawson
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BR
D000818:Animals; D015551:Autoimmunity / Q000502:physiology*; D018076:DNA, Complementary / Q000627:therapeutic use; D004195:Disease Models, Animal; D015316:Genetic Therapy; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000627:therapeutic use; D007371:Interferon-gamma / Q000502:physiology*; D007378:Interleukins / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D020239:Receptor Cross-Talk; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D018076:DNA, Complementary; D007141:Immunoglobulin Fc Fragments; D007378:Interleukins; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma