See accompanying article by Grifka-Walk et al. and commentary by Spath and Becher
T-bet is essential for Th1-mediated, but not Th17-mediated, CNS autoimmune disease
Article first published online: 21 AUG 2013
© 2013 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA Weinheim.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
European Journal of Immunology
Volume 43, Issue 11, pages 2818–2823, November 2013
How to Cite
O'Connor, R. A., Cambrook, H., Huettner, K. and Anderton, S. M. (2013), T-bet is essential for Th1-mediated, but not Th17-mediated, CNS autoimmune disease. Eur. J. Immunol., 43: 2818–2823. doi: 10.1002/eji.201343689
- Issue published online: 20 NOV 2013
- Article first published online: 21 AUG 2013
- Accepted manuscript online: 23 JUL 2013 12:58AM EST
- Manuscript Accepted: 17 JUL 2013
- Manuscript Revised: 14 JUN 2013
- Manuscript Received: 8 MAY 2013
- UK Medical Research Council and the Wellcome Trust to SMA
- T cells;
T cells that produce both IL-17 and IFN-γ, and co-express ROR-γt and T-bet, are often found at sites of autoimmune inflammation. However, it is unknown whether this co-expression of T-bet with ROR-γt is a prerequisite for immunopathology. We show here that T-bet is not required for the development of Th17-driven experimental autoimmune encephalomyelitis (EAE). The disease was not impaired in T-bet−/− mice and was associated with low IFN-γ production and elevated IL-17 production among central nervous system (CNS) infiltrating CD4+ T cells. T-bet−/− Th17 cells generated in the presence of IL-6/TGF-β/IL-1 and IL-23 produced GM-CSF and high levels of IL-17 and induced disease upon transfer to naïve mice. Unlike their WT counterparts, these T-bet−/– Th17 cells did not exhibit an IL-17IFN-γ switch upon reencounter with antigen in the CNS, indicating that this functional change is not critical to disease development. In contrast, T-bet was absolutely required for the pathogenicity of myelin-responsive Th1 cells. T-bet-deficient Th1 cells failed to accumulate in the CNS upon transfer, despite being able to produce GM-CSF. Therefore, T-bet is essential for establishing Th1-mediated inflammation but is not required to drive IL-23-induced GM-CSF production, or Th17-mediated autoimmune inflammation.