J. Exp. Med., Volume 188, Number 7, October 5, 1998 1369-1373

The Interleukin 2 Receptor  Chain/CD25 Promoter Is a Target for Nuclear Factor of Activated T Cells

By Kai Schuh,^* Thomas Twardzik,^* Burkhard Kneitz, Jörg Heyer,^* Anneliese Schimpl, and Edgar Serfling^*

From the ^* Institute of Pathology, and the  Institute of Virology and Immunobiology, University of Würzburg, D-97080 Würzburg, Germany

The expression of the murine interleukin (IL)-2 receptor  chain/CD25 is strongly induced at the transcriptional level after T cell activation. We show here that nuclear factor of activated T cell (NF-AT) factors are involved in the control of CD25 promoter induction in T cells. NF-ATp and NF-ATc bind to two sites around positions 585 and 650 located upstream of the proximal CD25 promoter. Immediately 3' from these NF-AT motifs, nonconsensus sites are located for the binding of AP-1-like factors. Mutations of sites that suppress NF-AT binding impair the induction and strong NF-ATp-mediated transactivation of the CD25 promoter in T cells. In T lymphocytes from NF-ATp-deficient mice, the expression of CD25 is severely impaired, leading to a delayed IL-2 receptor expression after T cell receptor (TCR)/CD3 stimulation. Our data indicate an important role for NF-AT in the faithful expression of high affinity IL-2 receptors and a close link between the TCR-mediated induction of IL-2 and IL-2 receptor  chain promoters, both of which are regulated by NF-AT factors.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Sumpter, T. L., Payne, K. K., Wilkes, D. S. (2008). Regulation of the NFAT pathway discriminates CD4+CD25+ regulatory T cells from CD4+CD25- helper T cells. J. Leukoc. Biol. 83: 708-717 [Abstract] [Full Text]  
• Chatzidakis, I., Fousteri, G., Tsoukatou, D., Kollias, G., Mamalaki, C. (2007). An Essential Role for TNF in Modulating Thresholds for Survival, Activation, and Tolerance of CD8+ T Cells. J. Immunol. 178: 6735-6745 [Abstract] [Full Text]  
• Perchonock, C. E., Fernando, M. C., Quinn, W. J. III, Nguyen, C. T., Sun, J., Shapiro, M. J., Shapiro, V. S. (2006). Negative Regulation of Interleukin-2 and p38 Mitogen-Activated Protein Kinase during T-Cell Activation by the Adaptor ALX.. Mol. Cell. Biol. 26: 6005-6015 [Abstract] [Full Text]  
• Falk, M., Ussat, S., Reiling, N., Wesch, D., Kabelitz, D., Adam-Klages, S. (2004). Caspase Inhibition Blocks Human T Cell Proliferation by Suppressing Appropriate Regulation of IL-2, CD25, and Cell Cycle-Associated Proteins. J. Immunol. 173: 5077-5085 [Abstract] [Full Text]  
• O'Sullivan, A., Chang, H.-C., Yu, Q., Kaplan, M. H. (2004). STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus. J. Biol. Chem. 279: 7339-7345 [Abstract] [Full Text]  
• Zeyda, M., Szekeres, A. B., Saemann, M. D., Geyeregger, R., Stockinger, H., Zlabinger, G. J., Waldhausl, W., Stulnig, T. M. (2003). Suppression of T Cell Signaling by Polyunsaturated Fatty Acids: Selectivity in Inhibition of Mitogen-Activated Protein Kinase and Nuclear Factor Activation. J. Immunol. 170: 6033-6039 [Abstract] [Full Text]  
• Neal, J. W., Clipstone, N. A. (2003). A Constitutively Active NFATc1 Mutant Induces a Transformed Phenotype in 3T3-L1 Fibroblasts. J. Biol. Chem. 278: 17246-17254 [Abstract] [Full Text]  
• Chen, J., Amasaki, Y., Kamogawa, Y., Nagoya, M., Arai, N., Arai, K.-i., Miyatake, S. (2003). Role of NFATx (NFAT4/NFATc3) in Expression of Immunoregulatory Genes in Murine Peripheral CD4+ T Cells. J. Immunol. 170: 3109-3117 [Abstract] [Full Text]  
• Hwang, E. S., White, I. A., Ho, I-C. (2002). An IL-4-independent and CD25-mediated function of c-maf in promoting the production of Th2 cytokines. Proc. Natl. Acad. Sci. USA 99: 13026-13030 [Abstract] [Full Text]  
• Porter, C. M., Clipstone, N. A. (2002). Sustained NFAT Signaling Promotes a Th1-Like Pattern of Gene Expression in Primary Murine CD4+ T Cells. J. Immunol. 168: 4936-4945 [Abstract] [Full Text]  
• Buggins, A. G. S., Milojkovic, D., Arno, M. J., Lea, N. C., Mufti, G. J., Thomas, N. S. B., Hirst, W. J. R. (2001). Microenvironment Produced by Acute Myeloid Leukemia Cells Prevents T Cell Activation and Proliferation by Inhibition of NF-{kappa}B, c-Myc, and pRb Pathways. J. Immunol. 167: 6021-6030 [Abstract] [Full Text]  
• Takahashi, I., Kosaka, H., Oritani, K., Heath, W. R., Ishikawa, J., Okajima, Y., Ogawa, M., Kawamoto, S.-i., Yamada, M., Azukizawa, H., Itami, S., Yoshikawa, K., Tomiyama, Y., Matsuzawa, Y. (2001). A New IFN-Like Cytokine, Limitin Modulates the Immune Response Without Influencing Thymocyte Development. J. Immunol. 167: 3156-3163 [Abstract] [Full Text]  
• Liu, J., Arai, K.-i., Arai, N. (2001). Inhibition of NFATx Activation by an Oligopeptide: Disrupting the Interaction of NFATx with Calcineurin. J. Immunol. 167: 2677-2687 [Abstract] [Full Text]  
• Kiani, A., Garcia-Cozar, F. J., Habermann, I., Laforsch, S., Aebischer, T., Ehninger, G., Rao, A. (2001). Regulation of interferon-{gamma} gene expression by nuclear factor of activated T cells. Blood 98: 1480-1488 [Abstract] [Full Text]  
• Pasare, C., Mukherjee, P., Verhoef, A., Bansal, P., Mendiratta, S. K., George, A., Lamb, J. R., Rath, S., Bal, V. (2001). T cells in mice expressing a transgenic human TCR{beta} chain get positively selected but cannot be activated in the periphery by signaling through TCR. Int Immunol 13: 53-62 [Abstract] [Full Text]  
• Cerdan, C., Serfling, E., Olive, D. (2000). The C-class chemokine, lymphotactin, impairs the induction of Th1-type lymphokines in human CD4+ T cells. Blood 96: 420-428 [Abstract] [Full Text]  
• Dengler, T. J., Pober, J. S. (2000). Human Vascular Endothelial Cells Stimulate Memory But Not Naive CD8+ T Cells to Differentiate into CTL Retaining an Early Activation Phenotype. J. Immunol. 164: 5146-5155 [Abstract] [Full Text]  
• Haynes, L., Linton, P.-J., Eaton, S. M., Tonkonogy, S. L., Swain, S. L. (1999). Interleukin 2, but Not Other Common {gamma} Chain–binding Cytokines, Can Reverse the Defect in Generation of CD4 Effector T Cells from Naive T Cells of Aged Mice. J. Exp. Med. 190: 1013-1024 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS