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Originally published in Science Express on 9 January 2003
Science 14 February 2003:
Vol. 299. no. 5609, pp. 1057 - 1061
DOI: 10.1126/science.1079490
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Reports

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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Regulatory T Cells Promote Early Influx of CD8+ T Cells in the Lungs of Respiratory Syncytial Virus-Infected Mice and Diminish Immunodominance Disparities.
T. J. Ruckwardt, K. L. Bonaparte, M. C. Nason, and B. S. Graham (2009)
J. Virol. 83, 3019-3028
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CD4+Foxp3+ T-Regulatory Cells in Noninfectious Uveitis.
S. Yeh, Z. Li, F. Forooghian, F. S. Hwang, M. A. Cunningham, S. Pantanelli, J. C. Lew, K. K. Wroblewski, S. Vitale, and R. B. Nussenblatt (2009)
Arch Ophthalmol 127, 407-413
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Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Inhibits Experimental Autoimmune Thyroiditis by the Expansion of CD4+CD25+ Regulatory T Cells.
S. H. Wang, G.-H. Chen, Y. Fan, M. Van Antwerp, and J. R. Baker Jr. (2009)
Endocrinology 150, 2000-2007
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NY-ESO-1 DNA Vaccine Induces T-Cell Responses That Are Suppressed by Regulatory T Cells.
S. Gnjatic, N. K. Altorki, D. N. Tang, S.-M. Tu, V. Kundra, G. Ritter, L. J. Old, C. J. Logothetis, and P. Sharma (2009)
Clin. Cancer Res. 15, 2130-2139
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Preferential Generation of Follicular B Helper T Cells from Foxp3+ T Cells in Gut Peyer's Patches.
M. Tsuji, N. Komatsu, S. Kawamoto, K. Suzuki, O. Kanagawa, T. Honjo, S. Hori, and S. Fagarasan (2009)
Science 323, 1488-1492
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Development of CD4+CD25+FoxP3+ regulatory T cells from cord blood hematopoietic progenitor cells.
J. F. Hutton, T. Gargett, T. J. Sadlon, S. Bresatz, C. Y. Brown, H. Zola, M. F. Shannon, R. J. D'Andrea, and S. C. Barry (2009)
J. Leukoc. Biol. 85, 445-451
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