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Continuous requirement for the TCR in regulatory T cell function

Nature Immunology volume 15, pages 10701078 (2014) | Download Citation

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Abstract

Foxp3+ regulatory T cells (Treg cells) maintain immunological tolerance, and their deficiency results in fatal multiorgan autoimmunity. Although heightened signaling via the T cell antigen receptor (TCR) is critical for the differentiation of Treg cells, the role of TCR signaling in Treg cell function remains largely unknown. Here we demonstrated that inducible ablation of the TCR resulted in Treg cell dysfunction that could not be attributed to impaired expression of the transcription factor Foxp3, decreased expression of Treg cell signature genes or altered ability to sense and consume interleukin 2 (IL-2). Instead, TCR signaling was required for maintaining the expression of a limited subset of genes comprising 25% of the activated Treg cell transcriptional signature. Our results reveal a critical role for the TCR in the suppressor capacity of Treg cells.

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Acknowledgements

We thank M. Schmidt-Supprian (Technical University Munich) and K. Rajewsky (Max Delbrück Center) for TracFL mice. Supported by the US National Institutes of Health (R37AI034206 to A.Y.R.), the Ludwig Cancer Center at Memorial Sloan-Kettering Cancer Center (A.Y.R.) and the Howard Hughes Medical Institute (A.Y.R.).

Author information

Author notes

    • Aaron Arvey
    •  & Wei Jin

    Present addresses: Gilead Sciences, Foster City, California, USA (A.A.) and Tsinghua University School of Medicine, Beijing, China (W.J.).

Affiliations

  1. Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

    • Andrew G Levine
    • , Aaron Arvey
    • , Wei Jin
    •  & Alexander Y Rudensky
  2. Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

    • Andrew G Levine
    • , Aaron Arvey
    • , Wei Jin
    •  & Alexander Y Rudensky
  3. Ludwig Center, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

    • Alexander Y Rudensky

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Contributions

A.G.L. and A.Y.R. designed the experiments; A.G.L. conducted experiments and wrote the manuscript; A.Y.R. supervised the research and edited the manuscript; and W.J. prepared samples for microarray analysis, and A.A. and A.G.L. conducted these analyses.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Alexander Y Rudensky.

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DOI

https://doi.org/10.1038/ni.3004

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