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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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CD4+CD25+ Foxp3+ Regulatory T Cells Protect against T Cell-Mediated Fulminant Hepatitis in a TGF-{beta}-Dependent Manner in Mice.
H.-X. Wei, Y.-H. Chuang, B. Li, H. Wei, R. Sun, Y. Moritoki, M. E. Gershwin, Z.-X. Lian, and Z. Tian (2008)
J. Immunol. 181, 7221-7229
   Abstract »    Full Text »    PDF »
Dendritic Cells Genetically Engineered to Express IL-10 Induce Long-Lasting Antigen-Specific Tolerance in Experimental Asthma.
E. Henry, C. J. Desmet, V. Garze, L. Fievez, D. Bedoret, C. Heirman, P. Faisca, F. J. Jaspar, P. Gosset, A. P. A. Jacquet, et al. (2008)
J. Immunol. 181, 7230-7242
   Abstract »    Full Text »    PDF »
Recent thymic origin, differentiation, and turnover of regulatory T cells.
N. H. E. Mabarrack, N. L. Turner, and G. Mayrhofer (2008)
J. Leukoc. Biol. 84, 1287-1297
   Abstract »    Full Text »    PDF »
Impact of Protective IL-2 Allelic Variants on CD4+Foxp3+ Regulatory T Cell Function In Situ and Resistance to Autoimmune Diabetes in NOD Mice.
E. Sgouroudis, A. Albanese, and C. A. Piccirillo (2008)
J. Immunol. 181, 6283-6292
   Abstract »    Full Text »    PDF »
Foxp3+ T-Regulatory Cells in Sjogren's Syndrome: Correlation with the Grade of the Autoimmune Lesion and Certain Adverse Prognostic Factors.
M. I. Christodoulou, E. K. Kapsogeorgou, N. M. Moutsopoulos, and H. M. Moutsopoulos (2008)
Am. J. Pathol. 173, 1389-1396
   Abstract »    Full Text »    PDF »
Thymus Exosomes-Like Particles Induce Regulatory T Cells.
G.-J. Wang, Y. Liu, A. Qin, S. V. Shah, Z.-b. Deng, X. Xiang, Z. Cheng, C. Liu, J. Wang, L. Zhang, et al. (2008)
J. Immunol. 181, 5242-5248
   Abstract »    Full Text »    PDF »
Spontaneous Colitis Occurrence in Transgenic Mice with Altered B7-Mediated Costimulation.
G. Kim, O. Turovskaya, M. Levin, F. R. Byrne, J. S. Whoriskey, J. G. McCabe, and M. Kronenberg (2008)
J. Immunol. 181, 5278-5288
   Abstract »    Full Text »    PDF »
Development of regulatory T cells requires IL-7R{alpha} stimulation by IL-7 or TSLP.
R. Mazzucchelli, J. A. Hixon, R. Spolski, X. Chen, W. Q. Li, V. L. Hall, J. Willette-Brown, A. A. Hurwitz, W. J. Leonard, and S. K. Durum (2008)
Blood 112, 3283-3292
   Abstract »    Full Text »    PDF »
CTLA-4 Control over Foxp3+ Regulatory T Cell Function.
K. Wing, Y. Onishi, P. Prieto-Martin, T. Yamaguchi, M. Miyara, Z. Fehervari, T. Nomura, and S. Sakaguchi (2008)
Science 322, 271-275
   Abstract »    Full Text »    PDF »
Update in Endocrine Autoimmunity.
M. S. Anderson (2008)
J. Clin. Endocrinol. Metab. 93, 3663-3670
   Abstract »    Full Text »    PDF »
The influence of IL-2 family cytokines on activation and function of naturally occurring regulatory T cells.
T. Y. Wuest, J. Willette-Brown, S. K. Durum, and A. A. Hurwitz (2008)
J. Leukoc. Biol. 84, 973-980
   Abstract »    Full Text »    PDF »
Regulatory T Cells Prevent Transfer of Type 1 Diabetes in NOD Mice Only When Their Antigen Is Present In Vivo.
D. R. Tonkin, J. He, G. Barbour, and K. Haskins (2008)
J. Immunol. 181, 4516-4522
   Abstract »    Full Text »    PDF »


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