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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}

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C. B. Collins, C. M. Aherne, E. N. McNamee, M. D. P. Lebsack, H. Eltzschig, P. Jedlicka, and J. Rivera-Nieves (2012)
Gut 61, 1154-1162
   Abstract »    Full Text »    PDF »
IL-2/IL-2Ab Complexes Induce Regulatory T Cell Expansion and Protect against Proteinuric CKD.
T. Polhill, G. Y. Zhang, M. Hu, A. Sawyer, J. J. Zhou, M. Saito, K. E. Webster, Y. Wang, Y. Wang, S. T. Grey, et al. (2012)
J. Am. Soc. Nephrol. 23, 1303-1308
   Abstract »    Full Text »    PDF »
Regulatory T cell properties of thymic CD4+CD25+ cells in turkeys.
R. Shanmugasundaram and R. K. Selvaraj (2012)
Poultry Science 91, 1833-1837
   Abstract »    Full Text »    PDF »
The T-cell Receptor Repertoire of Tumor-Infiltrating Regulatory T Lymphocytes Is Skewed Toward Public Sequences.
A. Sainz-Perez, A. Lim, B. Lemercier, and C. Leclerc (2012)
Cancer Res. 72, 3557-3569
   Abstract »    Full Text »    PDF »
Regulatory T-cell Modulation Using Cyclophosphamide in Vaccine Approaches: A Current Perspective.
D. T. Le and E. M. Jaffee (2012)
Cancer Res. 72, 3439-3444
   Abstract »    Full Text »    PDF »
Tim-3 Pathway Controls Regulatory and Effector T Cell Balance during Hepatitis C Virus Infection.
J. P. Moorman, J. M. Wang, Y. Zhang, X. J. Ji, C. J. Ma, X. Y. Wu, Z. S. Jia, K. S. Wang, and Z. Q. Yao (2012)
J. Immunol. 189, 755-766
   Abstract »    Full Text »    PDF »
Notch system in the linkage of innate and adaptive immunity.
T. Ito, J. M. Connett, S. L. Kunkel, and A. Matsukawa (2012)
J. Leukoc. Biol. 92, 59-65
   Abstract »    Full Text »    PDF »

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