Abstract
CD4+CD25highCD127low/– forkhead box p3 (Foxp3)+ regulatory T cells (Treg cells) possess functional plasticity. Here we describe a higher frequency of T helper type 1 (TH1)-like, interferon-γ (IFN-γ)-secreting Foxp3+ T cells in untreated subjects with relapsing remitting multiple sclerosis (RRMS) as compared to healthy control individuals. In subjects treated with IFN-β, the frequency of IFN-γ+Foxp3+ T cells is similar to that in healthy control subjects. In vitro, human Treg cells from healthy subjects acquire a TH1-like phenotype when cultured in the presence of interleukin-12 (IL-12). TH1-like Treg cells show reduced suppressive activity in vitro, which can partially be reversed by IFN-γ–specific antibodies or by removal of IL-12.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
McFarland, H.F. & Martin, R. Nat. Immunol. 8, 913–919 (2007).
Hafler, D.A. et al. N. Engl. J. Med. 312, 1405–1411 (1985).
Viglietta, V., Baecher-Allan, C., Weiner, H.L. & Hafler, D.A. J. Exp. Med. 199, 971–979 (2004).
Martinez-Forero, I. et al. Eur. J. Immunol. 38, 576–586 (2008).
Kumar, M. et al. J. Neuroimmunol. 180, 178–184 (2006).
Astier, A.L., Meiffren, G., Freeman, S. & Hafler, D.A. J. Clin. Invest. 116, 3252–3257 (2006).
Beriou, G. et al. Blood 113, 4240–4249 (2009).
Voo, K.S. et al. Proc. Natl. Acad. Sci. USA 106, 4793–4798 (2009).
Zhou, X. et al. Nat. Immunol. 10, 1000–1007 (2009).
Byrnes, A.A., McArthur, J.C. & Karp, C.L. Ann. Neurol. 51, 165–174 (2002).
Rabinovitch, A., Suarez-Pinzon, W.L. & Sorensen, O. J. Autoimmun. 9, 645–651 (1996).
Balashov, K.E., Smith, D.R., Khoury, S.J., Hafler, D.A. & Weiner, H.L. Proc. Natl. Acad. Sci. USA 94, 599–603 (1997).
Koch, M.A. et al. Nat. Immunol. 10, 595–602 (2009).
Beima, K.M. et al. J. Biol. Chem. 281, 11992–12000 (2006).
Loetscher, P. et al. Nature 391, 344–345 (1998).
Acknowledgements
We would like to thank K.C. O'Connor and members of the Hafler lab for valuable discussions and comments and D. Kozoriz for technical assistance. This work was supported by the US National Institutes of Health grants U19AI070352, R01NS024247, P01AI03971 and P01NS038037 (D.A.H.). D.A.H. is a Jacob Javits Scholar of the National Institute of Neurological Disorders and Stroke. C.M.B.-A. is supported by a Dana Scholars Grant from the Dana Foundation.
Author information
Authors and Affiliations
Contributions
M.D.-V. designed and performed the experiments, analyzed data and wrote the manuscript; C.M.B.-A. and D.A.H. supervised the study and wrote the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–15, Supplementary Table 1 and Supplementary Methods (PDF 546 kb)
Rights and permissions
About this article
Cite this article
Dominguez-Villar, M., Baecher-Allan, C. & Hafler, D. Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease. Nat Med 17, 673–675 (2011). https://doi.org/10.1038/nm.2389
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nm.2389
This article is cited by
-
A randomized double-blind placebo-controlled trial of low-dose interleukin-2 in relapsing–remitting multiple sclerosis
Journal of Neurology (2023)
-
Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19
Nature Communications (2022)
-
Direct AKT activation in tumor-infiltrating lymphocytes markedly increases interferon-γ (IFN-γ) for the regression of tumors resistant to PD-1 checkpoint blockade
Scientific Reports (2022)
-
PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration
Nature Communications (2022)
-
The immunology of multiple sclerosis
Nature Reviews Immunology (2022)