Journal
EXPERIMENTAL NEUROLOGY
Volume 220, Issue 2, Pages 366-373Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2009.09.022
Keywords
T-bet; T helper cells; EAMG; Autoimmunity; Autoantibody; CD4(+)CD25(+) regulatory T cells
Categories
Funding
- Muscular Dystrophy Association
- Barrow Neurological Foundation
- China Scholarship Council [2008620028]
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T-bet, a tissue-specific transcription factor, controls T helper 1 (Th1) cell differentiation and IFN-production. Given the reciprocal relationship between Th1 and other types of helper T cells, we hypothesized that T-bet impacts multiple helper and regulatory T (Treg) cells, thereby influencing the magnitude of autoimmune disease. We tested this hypothesis in an experimental model of autoimmune myasthenia gravis (FAMG) of mice. Myasthenia gravis (MG) and EAMG are T cell-driven, IgG autoantibody-mediated disorders that destroy muscles by attacking the target antigen acetylcholine receptor (AChR) or other antigens of skeletal muscle at neuromuscular junctions. We show that, compared to wild-type mice, AChR-primed T-bet(-/-) mice are less susceptible to EAMG. This phenotype is associated with a reduction of autoreactive Th1 cells and augmentation of Th2 and Th17 cells as well as an upregulation of Foxp3 expression by T-bet(-/-)CD4(+)CD25(+) Treg cells. Thus, in our model, T-bet not only specifies the Th1 lineage but also has a broad influence on autoreactive Th2, Th17 and Treg cells. These coordinated effects reduce the genesis of pathogenic antibodies and protect against B cell-mediated EAMG. (C) 2009 Elsevier Inc. All rights reserved.
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