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¹ Department of Immunology, University of Washington, Seattle, WA 98195
² Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195
³ Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, MD 20892

CORRESPONDENCE Alexander Y. Rudensky: aruden{at}u.washington.edu

Transforming growth factor (TGF)-ß1 is a major pluripotential cytokine with a pronounced immunosuppressive effect and its deficiency results in lethal autoimmunity in mice. However, mechanisms of its immunosuppressive action are not completely understood. Here, we report that TGF-ß1 supports the maintenance of Foxp3 expression, regulatory function, and homeostasis in peripheral CD4⁺CD25⁺ regulatory T (T reg) cells, but is not required for their thymic development. We found that in 8–10-d-old TGF-ß1–deficient mice, peripheral, but not thymic, T reg cells are significantly reduced in numbers. Moreover, our experiments suggest that a defect in TGF-ß–mediated signaling in T reg cells is associated with a decrease in Foxp3 expression and suppressor activity. Thus, our results establish an essential link between TGF-ß1 signaling in peripheral T reg cells and T reg cell maintenance in vivo.

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• Maggio-Price, L., Treuting, P., Zeng, W., Tsang, M., Bielefeldt-Ohmann, H., Iritani, B. M. (2006). Helicobacter Infection Is Required for Inflammation and Colon Cancer in Smad3-Deficient Mice. Cancer Res. 66: 828-838 [Abstract] [Full Text]  
• Duplan, V., Beriou, G., Heslan, J.-M., Bruand, C., Dutartre, P., Mars, L. T., Liblau, R. S., Cuturi, M.-C., Saoudi, A. (2006). LF 15-0195 Treatment Protects against Central Nervous System Autoimmunity by Favoring the Development of Foxp3-Expressing Regulatory CD4 T Cells. J. Immunol. 176: 839-847 [Abstract] [Full Text]  
• Huang, X., Zhu, J., Yang, Y. (2005). Protection against Autoimmunity in Nonlymphopenic Hosts by CD4+CD25+ Regulatory T Cells Is Antigen-Specific and Requires IL-10 and TGF-{beta}. J. Immunol. 175: 4283-4291 [Abstract] [Full Text]  
• Nishikawa, H., Kato, T., Tawara, I., Ikeda, H., Kuribayashi, K., Allen, P. M., Schreiber, R. D., Old, L. J., Shiku, H. (2005). IFN-{gamma} Controls the Generation/Activation of CD4+CD25+ Regulatory T Cells in Antitumor Immune Response. J. Immunol. 175: 4433-4440 [Abstract] [Full Text]  

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