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


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.

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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.

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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.

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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.

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Correspondence to David A Hafler.

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The authors declare no competing financial interests.

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Supplementary Figures 1–15, Supplementary Table 1 and Supplementary Methods (PDF 546 kb)

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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).

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