Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease

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

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

Figure 1: Treg cells from individuals with RRMS secrete IFN-γ ex vivo.
Figure 2: Characterization of IL-12–driven, IFN-γ+Foxp3+ Treg cells in vitro from healthy controls.

Similar content being viewed by others

References

  1. McFarland, H.F. & Martin, R. Nat. Immunol. 8, 913–919 (2007).

    Article  CAS  Google Scholar 

  2. Hafler, D.A. et al. N. Engl. J. Med. 312, 1405–1411 (1985).

    Article  CAS  Google Scholar 

  3. Viglietta, V., Baecher-Allan, C., Weiner, H.L. & Hafler, D.A. J. Exp. Med. 199, 971–979 (2004).

    Article  CAS  Google Scholar 

  4. Martinez-Forero, I. et al. Eur. J. Immunol. 38, 576–586 (2008).

    Article  CAS  Google Scholar 

  5. Kumar, M. et al. J. Neuroimmunol. 180, 178–184 (2006).

    Article  CAS  Google Scholar 

  6. Astier, A.L., Meiffren, G., Freeman, S. & Hafler, D.A. J. Clin. Invest. 116, 3252–3257 (2006).

    Article  CAS  Google Scholar 

  7. Beriou, G. et al. Blood 113, 4240–4249 (2009).

    Article  CAS  Google Scholar 

  8. Voo, K.S. et al. Proc. Natl. Acad. Sci. USA 106, 4793–4798 (2009).

    Article  CAS  Google Scholar 

  9. Zhou, X. et al. Nat. Immunol. 10, 1000–1007 (2009).

    Article  CAS  Google Scholar 

  10. Byrnes, A.A., McArthur, J.C. & Karp, C.L. Ann. Neurol. 51, 165–174 (2002).

    Article  CAS  Google Scholar 

  11. Rabinovitch, A., Suarez-Pinzon, W.L. & Sorensen, O. J. Autoimmun. 9, 645–651 (1996).

    Article  CAS  Google Scholar 

  12. Balashov, K.E., Smith, D.R., Khoury, S.J., Hafler, D.A. & Weiner, H.L. Proc. Natl. Acad. Sci. USA 94, 599–603 (1997).

    Article  CAS  Google Scholar 

  13. Koch, M.A. et al. Nat. Immunol. 10, 595–602 (2009).

    Article  CAS  Google Scholar 

  14. Beima, K.M. et al. J. Biol. Chem. 281, 11992–12000 (2006).

    Article  CAS  Google Scholar 

  15. Loetscher, P. et al. Nature 391, 344–345 (1998).

    Article  CAS  Google Scholar 

Download references

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

Authors

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

Correspondence to David A Hafler.

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

Reprints 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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm.2389

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing