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Blood, 1 February 2006, Vol. 107, No. 3, pp. 987-993. Prepublished online as a Blood First Edition Paper on October 6, 2005; DOI 10.1182/blood-2005-07-2834. This Article Full Text (PDF) All Versions of this Article: 2005-07-2834v1 107/3/987    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gil, M. P. Articles by Biron, C. A Search for Related Content PubMed PubMed Citation Articles by Gil, M. P. Articles by Biron, C. A Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 18, 2005 Accepted September 11, 2005 Modulation of STAT1 protein levels: A mechanism shaping CD8 t cell responses in vivo M. Pilar Gil, Rachelle Salomon, Jennifer Louten, and Christine A Biron* Department of Molecular Microbiology & Immunology, Division of Biology and Medicine, Brown University, Providence, RI, USA * Corresponding author; email: Christine_Biron{at}brown.edu. Type 1 interferons (IFNs) are induced in vivo, administered therapeutically, and potential targets for amelioration of autoimmune diseases. The cytokines mediate profound anti-proliferative effects. STAT1-dependent signaling pathways are required for inhibition of proliferation, and viral infections can elicit high levels of type 1 IFNs as well as total STAT1 protein expression. Thus, a mechanism must be in place to help antigen-specific T cells overcome IFN-induced inhibition of proliferation. The studies reported here demonstrate that total CD8 T cell proliferation in the presence of IFNs, ex vivo in response to cytokines and in vivo during viral infection, is inhibited through a STAT1-dependent mechanism. In contrast, major proportions of antigen-specific CD8, but not CD4, T cells are rendered less sensitive to this inhibition, express lower endogenous levels of total STAT1, and are selectively proliferating in the presence of type 1 IFN, at key times after viral challenge. Taken together, these novel results show that differential STAT1 expression is used by the immune system to modify cytokine-mediated effects on T cell expansion, and have implications for the consequences of therapeutic intervention in cytokine function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Ignoring type 1 interferons Joan E. Durbin Blood 2006 107: 847-848. [Full Text] [PDF] This article has been cited by other articles: A. Pilz, W. Kratky, S. Stockinger, O. Simma, U. Kalinke, K. Lingnau, A. von Gabain, D. Stoiber, V. Sexl, T. Kolbe, et al. Dendritic Cells Require STAT-1 Phosphorylated at Its Transactivating Domain for the Induction of Peptide-Specific CTL J. Immunol., August 15, 2009; 183(4): 2286 - 2293. [Abstract] [Full Text] [PDF] T. Demoulins, A. Abdallah, N. Kettaf, M.-L. Baron, C. Gerarduzzi, D. Gauchat, S. Gratton, and R.-P. Sekaly Reversible Blockade of Thymic Output: An Inherent Part of TLR Ligand-Mediated Immune Response J. Immunol., November 15, 2008; 181(10): 6757 - 6769. [Abstract] [Full Text] [PDF] M. Quigley, X. Huang, and Y. Yang STAT1 Signaling in CD8 T Cells Is Required for Their Clonal Expansion and Memory Formation Following Viral Infection In Vivo J. Immunol., February 15, 2008; 180(4): 2158 - 2164. 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Jahnsen, and J. Olweus Plasmacytoid DCs regulate recall responses by rapid induction of IL-10 in memory T cells Blood, April 15, 2007; 109(8): 3369 - 3376. [Abstract] [Full Text] [PDF] A. A. Byrnes, D.-Y. Li, K. Park, D. Thompson, C. Mocilnikar, P. Mohan, J. P. Molleston, M. Narkewicz, H. Zhou, S. F. Wolf, et al. Modulation of the IL-12/IFN-{gamma} axis by IFN-{alpha} therapy for hepatitis C J. Leukoc. Biol., March 1, 2007; 81(3): 825 - 834. [Abstract] [Full Text] [PDF] L. S. Berenson, M. Gavrieli, J. D. Farrar, T. L. Murphy, and K. M. Murphy Distinct Characteristics of Murine STAT4 Activation in Response to IL-12 and IFN-{alpha} J. Immunol., October 15, 2006; 177(8): 5195 - 5203. [Abstract] [Full Text] [PDF] H. H. Ho and L. B. Ivashkiv Role of STAT3 in Type I Interferon Responses: NEGATIVE REGULATION OF STAT1-DEPENDENT INFLAMMATORY GENE ACTIVATION J. Biol. Chem., May 19, 2006; 281(20): 14111 - 14118. [Abstract] [Full Text] [PDF] A. Garcia-Sastre and C. A. Biron Type 1 interferons and the virus-host relationship: a lesson in detente . Science, May 12, 2006; 312(5775): 879 - 882. [Abstract] [Full Text] [PDF]

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