This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gimeno, R. Articles by Levy, D. E. Search for Related Content PubMed PubMed Citation Articles by Gimeno, R. Articles by Levy, D. E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2005, p. 5456-5465, Vol. 25, No. 13
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.13.5456-5465.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Stat1 and Stat2 but Not Stat3 Arbitrate Contradictory Growth Signals Elicited by Alpha/Beta Interferon in T Lymphocytes

Ramon Gimeno,^1, Chien-Kuo Lee,^1, Christian Schindler,² and David E. Levy^1*

Departments of Pathology and Microbiology, New York University School of Medicine, New York, New York 10016,¹ Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032²

Received 26 January 2005/ Returned for modification 17 March 2005/ Accepted 11 April 2005

Alpha/beta interferon (IFN-/ß) triggers antiviral and antiproliferative responses in target cells through modulation of gene expression. The JAK-STAT pathway is the major mediator of these biological effects through the activation of the transcription factors STAT1 and STAT2, and gene ablation studies have demonstrated that both STAT1 and STAT2 are required for most antiviral responses induced by IFN-/ß. However, additional signaling pathways are also activated by IFN. Here, we show that these additional pathways provoke a proliferative response in activated T lymphocytes. While activation of IFN-stimulated gene factor 3 produces a dominant inhibitory signal capable of overriding the mitogenic response, absence of either STAT1 or STAT2 leads to a proliferative response to IFN. Growth stimulation by IFN-/ß is independent of other STAT proteins, particularly of STAT3, since T lymphocytes from STAT1-STAT3 double-knockout mice are growth stimulated by IFN-/ß treatment. IFN-/ß can cooperate with numerous T-cell mitogens, including interleukin-2 (IL-2), IL-4, IL-7, and IL-12, and can contribute to the rapid restoration of the thymus following glucocorticoid-mediated ablation. These results underscore the complexity of the cellular response to IFN and suggest that the ultimate outcome of IFN action results from a balance between growth-inhibitory and -stimulatory effects.

Present address: Department of Cell Biology and Histology, University of Amsterdam, Amsterdam, The Netherlands.

Present address: Institute of Immunology, National Taiwan University College of Medicine, Taipei 100, Taiwan.

This article has been cited by other articles:

• Zhao, W., Lee, C., Piganis, R., Plumlee, C., de Weerd, N., Hertzog, P. J., Schindler, C. (2008). A Conserved IFN-{alpha} Receptor Tyrosine Motif Directs the Biological Response to Type I IFNs. J. Immunol. 180: 5483-5489 [Abstract] [Full Text]  
• Zeng, R., Spolski, R., Casas, E., Zhu, W., Levy, D. E., Leonard, W. J. (2007). The molecular basis of IL-21-mediated proliferation. Blood 109: 4135-4142 [Abstract] [Full Text]  
• Ho, H. H., Ivashkiv, L. B. (2006). Role of STAT3 in Type I Interferon Responses: NEGATIVE REGULATION OF STAT1-DEPENDENT INFLAMMATORY GENE ACTIVATION. J. Biol. Chem. 281: 14111-14118 [Abstract] [Full Text]  
• Garcia-Sastre, A., Biron, C. A. (2006). Type 1 interferons and the virus-host relationship: a lesson in detente .. Science 312: 879-882 [Abstract] [Full Text]  
• Gil, M. P., Salomon, R., Louten, J., Biron, C. A. (2006). Modulation of STAT1 protein levels: a mechanism shaping CD8 T-cell responses in vivo. Blood 107: 987-993 [Abstract] [Full Text]