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Regulatory T cells: roles of T cell receptor for their development and function

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Abstract

Naturally arising CD4+CD25+ regulatory T cells (Treg cells), which specifically express the forkhead family transcription factor Foxp3, are essential for the maintenance of immunological self-tolerance and immune homeostasis. Stimulation of the T cell antigen receptor (TCR) via recognizing self-peptide/major histocompatibility complex (MHC) is required for their expression of Foxp3 in the course of their development in the thymus. The TCR repertoires displayed by Treg cells and naïve T cells are apparently distinct, suggesting that Treg cells with high reactivity to self-peptide/MHC ligands are somehow driven to Treg cell lineage in the thymus. Treg cells also require stimulation via TCR to exert suppression in the periphery. At the molecular level, assembly of Foxp3, Foxp3-interacting factors, and chromatin-remodeling factors is in part under the control of TCR signaling, and TCR stimulation alters Foxp3-dependent transcriptional regulation, protein–protein interaction, and Foxp3 recruitment to the specific genomic loci. These findings collectively indicate that the TCR signaling is essential for suppressive function of Treg cells and that TCR has a determinant role for driving developing T cells to the Foxp3+CD4+CD25+ Treg cell lineage and differentiation.

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Acknowledgements

The authors have no conflicting financial interests. We thank Atsushi Tanaka for critically reading the manuscript. This work was supported by grants-in-aids from the Ministry of Education, Sports, and Culture and the Ministry of Human Welfare of Japan.

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  1. Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Naganari Ohkura & Shimon Sakaguchi

  2. WPI Immunology Frontier Research Center, Osaka University, Suita, 565-0871, Japan

    Naganari Ohkura & Shimon Sakaguchi

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  1. Naganari Ohkura
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Correspondence to Shimon Sakaguchi.

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Ohkura, N., Sakaguchi, S. Regulatory T cells: roles of T cell receptor for their development and function. Semin Immunopathol 32, 95–106 (2010). https://doi.org/10.1007/s00281-010-0200-5

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