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Science 299 (5609): 1057-1061

Copyright © 2003 by the American Association for the Advancement of Science

Control of Regulatory T Cell Development by the Transcription Factor Foxp3

Shohei Hori,1 Takashi Nomura,2 Shimon Sakaguchi12*

Regulatory T cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Little is known, however, about the molecular mechanism of their development. Here we show that Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells. Furthermore, retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+ regulatory T cells. Thus, Foxp3 is a key regulatory gene for the development of regulatory T cells.

1 Laboratory of Immunopathology, Research Center for Allergy and Immunology, Institute for Physical and Chemical Research, Yokohama 230-0045, Japan.
2 Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
*   To whom correspondence should be addressed. E-mail: shimon{at}frontier.kyoto-u.ac.jp

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Identification of Human Regulatory T Cells in the Setting of T-Cell Activation and Anti-CTLA-4 Immunotherapy on the Basis of Expression of Latency-Associated Peptide.
J. Sun, D. N. Tang, T. Fu, and P. Sharma (2012)
Cancer Discovery 2, 122-130
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ICOS-Dependent Homeostasis and Function of Foxp3+ Regulatory T Cells in Islets of Nonobese Diabetic Mice.
M. Kornete, E. Sgouroudis, and C. A. Piccirillo (2012)
J. Immunol. 188, 1064-1074
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Scaffold protein Disc large homolog 1 is required for T-cell receptor-induced activation of regulatory T-cell function.
A. Zanin-Zhorov, J. Lin, J. Scher, S. Kumari, D. Blair, K. L. Hippen, B. R. Blazar, S. B. Abramson, J. J. Lafaille, and M. L. Dustin (2012)
PNAS 109, 1625-1630
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Potent Induction of Tumor Immunity by Combining Tumor Cryoablation with Anti-CTLA-4 Therapy.
R. Waitz, S. B. Solomon, E. N. Petre, A. E. Trumble, M. Fasso, L. Norton, and J. P. Allison (2012)
Cancer Res. 72, 430-439
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