Distinct roles of helper T-cell subsets in a systemic autoimmune disease.
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-gamma (IFN-gamma) 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-gamma, delays the development of AIHA. Further, CD4(+) T cells from IL-2/IFN-gamma-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.
Hoyer
Katrina K
KK
Department of Pathology, University of California San Francisco, CA 94143, USA.
Kuswanto
Wilson F
WF
Gallo
Eugenio
E
Abbas
Abul K
AK
D000208:Acute Disease; D000744:Anemia, Hemolytic, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007410:Intestinal Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D016207:Cytokines