SEARCH:   Advanced

Blood, 1 October 2007, Vol. 110, No. 7, pp. 2528-2536. Prepublished online as a Blood First Edition Paper on July 3, 2007; DOI 10.1182/blood-2006-08-041541. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-08-041541v1 110/7/2528    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Brender, C. Articles by Starr, R. Search for Related Content PubMed PubMed Citation Articles by Brender, C. Articles by Starr, R. Related Collections Signal Transduction Chemokines, Cytokines, and Interleukins Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Suppressor of cytokine signaling 3 regulates CD8 T-cell proliferation by inhibition of interleukins 6 and 27 Christine Brender1, Gillian M. Tannahill1, Brendan J. Jenkins2, Joel Fletcher1, Ruth Columbus3, Christiaan J. M. Saris4, Matthias Ernst5, Nicos A. Nicola3, Douglas J. Hilton6, Warren S. Alexander3, and Robyn Starr1 1 Signal Transduction Laboratory, St Vincent's Institute, Fitzroy, Victoria, Australia; 2 Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia; 3 Division of Cancer and Haemotology, The Walter and Eliza Hall Institute, Parkville, Victoria, Australia; 4 Department of Inflammation Research, Amgen, Thousand Oaks, CA; 5 Colon Molecular and Cell Biology Laboratory, Ludwig Institute for Cancer Research, Parkville, Victoria, Australia; 6 Molecular Medicine Division, The Walter and Eliza Hall Institute, Parkville, Victoria, Australia Suppressor of cytokine signaling (SOCS) proteins regulate the intensity and duration of cytokine responses. SOCS3 is expressed in peripheral T cells, and recent reports have suggested that overexpression of SOCS3 modulates antigen- and/or costimulation-induced T-cell activation. To study the role of SOCS3 in the regulation of T-cell activation, we used a conditional gene-targeting strategy to generate mice that lack SOCS3 in T/natural killer T cells (Socs3Lck/Lck mice). SOCS3-deficient CD8 T cells showed greater proliferation than wild-type cells in response to T-cell receptor (TCR) ligation despite normal activation of signaling pathways downstream from TCR or CD28 receptors. Signaling in response to the gp130 cytokines interleukin (IL)–6 and IL-27 was prolonged in Socs3Lck/Lck T cells, and T cells from gp130Y757F/Y757F mice, in which the SOCS3-binding site on gp130 is ablated, showed a striking similarity to SOCS3-deficient CD8 T cells. Although the proliferative defect of Socs3Lck/Lck T cells was not rescued in the absence of IL-6, suppression of IL-27 signaling was found to substantially reduce anti-CD3–induced proliferation. We conclude that enhanced responses to TCR ligation by SOCS3-deficient CD8 T cells are not caused by aberrant TCR-signaling pathways but, rather, that increased IL-27 signaling drives unregulated proliferation in the absence of SOCS3. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Owaki, M. Asakawa, N. Morishima, I. Mizoguchi, F. Fukai, K. Takeda, J. Mizuguchi, and T. Yoshimoto STAT3 Is Indispensable to IL-27-Mediated Cell Proliferation but Not to IL-27-Induced Th1 Differentiation and Suppression of Proinflammatory Cytokine Production J. Immunol., March 1, 2008; 180(5): 2903 - 2911. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020