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 invol ved in autoantibody( humoral)-mediated autoimmune diseases. However, this p aradigm has been refuted by recent studies in several induced and spontaneo us mouse models of systemic lupus erythematosus, which showed that IFN-gamm a is a major effector molecule in this disease. These and additional findin gs, reviewed here, suggest that these two cross-talking classes of cytokine s can exert autoimmune disease-promoting or disease-inhibiting effects with out predictability or strict adherence to the Th1-versus-Th2 dualism.