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Induction of T helper type 1–like regulatory cells that express Foxp3 and protect against airway hyper-reactivity

Nature Immunology volume 5, pages 1149–1156 (2004)Cite this article

Abstract

The range of regulatory T cell (TR cell) types that control immune responses is poorly understood. We describe here a population of TR cells that developed in vivo from naive CD4+CD25− T cells during a T helper type 1 (TH1)–polarized response, distinct from CD25+ TR cells. These antigen-specific TR cells were induced by CD8α+ DCs, produced both interleukin 10 and interferon-γ, and potently inhibited the development of airway hyper-reactivity. These TR cells expressed the transcription factors Foxp3 and T-bet, indicating that these TR cells are related to TH1 cells. Thus, adaptive TR cells are heterogeneous and comprise TH1-like TR cells as well as previously described TH2-like TR cells, which express Foxp3 and are induced during the development of respiratory tolerance by CD8α− DCs.

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Figure 1: CD11c+ CD8α+ DCs protect against AHR.
Figure 2: T cells induced by the regulatory CD8α+ DC express IL-10 and IFN-γ.
Figure 3: IL-10-producing T cells express CD25, ICOS, Foxp3 and T-bet.
Figure 4: TR cells inhibit AHR and airway inflammation.
Figure 5: The regulatory effects of the TR cells depend on IL-10 but not IFN-γ.
Figure 6: TR cells suppress naive and effector T cells.

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Acknowledgements

This work was supported by National Institutes of Health Public Health Service (AI26322 to D.T.U., HL62348 to D.T.U., HL69507 to R.H.D. and CA84500 and AI39671 to G.J.F.), Deutsche Forschungsgemeinschaft (STO 467/2-1 to P.S.) and American Lung Association of California (O.A.)

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Author notes

  1. Omid Akbari, Rosemarie H DeKruyff & Dale T Umetsu

    Present address: Division of Immunology, Children's Hospital Boston, Karp Research Building, Harvard Medical School, Boston, Massachusetts, 02115-5737, USA

  2. Philippe Stock

    Present address: Department of Pediatric Pneumology and Immunology, University Hospital Charité, Augustenburger Platz 1, 13353, Berlin, Germany

Authors and Affiliations

  1. Division of Immunology and Allergy, Department of Pediatrics, Stanford University, Stanford, 94305-5208, California, USA

    Philippe Stock, Omid Akbari, Rosemarie H DeKruyff & Dale T Umetsu

  2. Department of Pathology, Stanford University, Stanford, 94305-5208, California, USA

    Gerald Berry

  3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    Gordon J Freeman

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Correspondence to Dale T Umetsu.

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Supplementary information

Supplementary Fig. 1

CD8α+ DCs from mice immunized with OVA + HKL show a mature phenotype. (PDF 163 kb)

Supplementary Fig. 2

TH1-like Regulatory cells secrete IL-10. (PDF 490 kb)

Supplementary Table 1

The Number of DO11.10 T Cells Producing IL-10 and IFN-γ Recovered from Recipient Mice (PDF 53 kb)

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Stock, P., Akbari, O., Berry, G. et al. Induction of T helper type 1–like regulatory cells that express Foxp3 and protect against airway hyper-reactivity. Nat Immunol 5, 1149–1156 (2004). https://doi.org/10.1038/ni1122

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