Distinct roles of helper T-cell subsets in a systemic autoimmune disease

Abstract

Abstract Imbalance of T-helper cell (Th) differentiation and subsequent cytokine dysregulation is implicated in inflammatory and autoimmune diseases. In particular, 2 cytokines produced by different Th cell populations, interferon-γ (IFN-γ) and interleukin-17 (IL-17), have been shown to play a critical role in autoimmunity. We have examined the roles of these cytokines in a mouse model of systemic autoimmunity resulting from the deletion of IL-2 in which autoimmune hemolytic anemia (AIHA) is a prominent feature. We demonstrate that, in IL-2–knockout (KO) BALB/c mice, elimination of the Th1 cytokine, IFN-γ, delays the development of AIHA. Further, CD4+ T cells from IL-2/IFN-γ–KO mice produce elevated levels of IL-17 compared with wild-type (WT) and IL-2–KO, and these mice eventually develop intestinal inflammation. In contrast, elimination of the Th17 cytokine, IL-17, from IL-2–KO mice fails to suppress early acute AIHA development. These results suggest that in a systemic autoimmune disease with multiple manifestations, Th1 cells drive the early autoantibody response and IL-17–producing cells may be responsible for the more chronic tissue inflammation.