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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 14, 2006 Accepted June 20, 2007 SOCS3 regulates CD8 T cell proliferation by inhibition of IL-6 and IL-27 Christine Brender, Gillian M Tannahill, Brendan J Jenkins, Joel Fletcher, Ruth Columbus, Christiaan JM Saris, Matthias Ernst, Nicos A Nicola, Douglas J Hilton, Warren S Alexander, and Robyn Starr* Signal Transduction Laboratory, St Vincent's Institute, Fitzroy, Australia Centre for Functional Genomics and Human Disease, Monash Institute of Medical Research, Monash University, Clayton, Australia Division of Cancer and Haematology, The Walter and Eliza Hall Institute, Parkville, Australia Department of Inflammation Research, Amgen, Thousand Oaks, United States Colon Molecular and Cell Biology Laboratory, Ludwig Institute for Cancer Research, Parkville, Australia Division of Molecular Medicine, The Walter and Eliza Hall Institute, Parkville, Australia * Corresponding author; email: rstarr{at}svi.edu.au. Suppressor of cytokine signalling (SOCS) proteins regulate the intensity and duration of cytokine responses. SOCS3 is expressed in peripheral T cells, and recent reports suggest that overexpression of SOCS3 modulates antigen- and/or co-stimulation-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 lacking SOCS3 in T/NKT cells (Socs3Lck/Lck mice). SOCS3-deficient CD8 T cells showed greater proliferation than wildtype cells in response to TCR ligation, despite normal activation of signalling pathways downstream from TCR or CD28 receptors. Signalling in response to the gp130 cytokines 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 signalling 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 due to aberrant TCR signalling pathways, but rather that increased IL-27 signalling 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]

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