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J. Biol. Chem., Vol. 278, Issue 25, 22755-22761, June 20, 2003
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Suppressor of Cytokine Signaling-1 Regulates Signaling in Response to Interleukin-2 and Other 
c-dependent Cytokines in Peripheral T Cells*
From the
The Walter and Eliza Hall Institute of Medical Research and Cooperative Research Centre for Cellular Growth Factors, Post Office, Royal Melbourne Hospital, Victoria 3050, Australia
Suppressor of cytokine signaling-1 (SOCS-1) is an essential regulator of cytokine signaling. SOCS-1-/- mice die before weaning with a complex disease characterized by fatty degeneration and necrosis of the liver. This disease is mediated by interferon (IFN) 
as neonatal mortality fails to occur in SOCS-1-/-IFN-/- mice. However, the immune system of healthy SOCS-1-/-IFN-/- mice is dysregulated with a reduced ratio of CD4:CD8 T cells and increases in some aspects of T cell activation. SOCS-1-/-IFN-/- mice also die before their wild type and IFN-/- counterparts with a range of inflammatory conditions including pneumonia, gut infiltration, and skin ulceration, suggesting that SOCS-1 controls not only IFN signaling, but also other immunoregulatory factors. This study shows that T cells from SOCS-1-deficient mice display hypersensitivity to cytokines that act through the c receptor. SOCS-1 expression is induced by interleukin (IL) 2, IL-4, IL-7, and IL-15, and SOCS-1-deficient T cells show increased proliferation and prolonged survival in response to IL-2 and IL-4. Furthermore, IL-2 induced increased STAT5 phosphorylation and CD44 expression in SOCS-1-deficient T cells compared with controls. Hypersensitivity to c-dependent cytokines may contribute to abnormal T cell function, as well as the pathology observed in mice lacking SOCS-1.
Received for publication, March 24, 2003
* This work was supported by the National Health and Medical Research Council, Canberra, Australia, National Institutes of Health Grant CA-22556, the Australian Federal Government Cooperative Research Centres Program, and National Health and Medical Research Council Program Grant 257500. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
To whom correspondence should be addressed: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3050, Victoria, Australia. Tel.: 61-3-9345-2555; Fax: 61-3-93452616; E-mail: alexandw{at}wehi.edu.au.
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