SOCS-1 protects from virally-induced CD8 T cell mediated type 1 diabetes

J Autoimmun. 2006 Nov;27(3):166-73. doi: 10.1016/j.jaut.2006.08.002. Epub 2006 Oct 10.


CD8(+) cytotoxic T lymphocytes (CTL) can rapidly kill beta-cells and therefore contribute to the development of type 1 diabetes (T1D). CTL-mediated beta-cell killing can occur via perforin-mediated lysis, Fas-Fas-L interaction, and the secretion of TNF-alpha or IFN-gamma. The secretion of IFN-gamma can contribute to beta-cell death directly by eliciting nitric oxide production, and indirectly by upregulating MHC class I and 'unmasking' beta-cells for recognition by CTL. Earlier studies in the RIP-LCMV mouse model of diabetes showed that disruption of beta-cell IFN-gamma signaling alone abolished the direct detrimental effects of IFN-gamma, but not MHC class I upregulation. Suppressor of cytokine signaling-1 (SOCS-1) represses several crucial cytokine signaling pathways simultaneously, among them IFN-gamma and IL-1-beta. We therefore evaluated the protective capacity of islet cell SOCS-1 expression in the CD8(+) mediated RIP-LCMV diabetes model. Clinical disease was prevented in over 90% of the mice. Not only absence of MHC-I and Fas upregulation, but also resistance to cytokine-induced killing of beta-cells and a complete lack of CXCL-10 (IP10) production in islets led to a lack of islet infiltration and impaired activation of autoaggressive CD4(+) and CD8(+) T-cells in these mice. Thus, SOCS expression renders beta-cells resistant to CTL attack in a mouse model of T1D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytotoxicity, Immunologic
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / virology
  • Disease Models, Animal
  • Flow Cytometry
  • Histocompatibility Antigens Class I / biosynthesis
  • Immunohistochemistry
  • Insulin-Secreting Cells / metabolism*
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology
  • Lymphocytic choriomeningitis virus
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics
  • Receptors, Cytokine / biosynthesis
  • Signal Transduction / physiology
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / biosynthesis*
  • fas Receptor / biosynthesis


  • Histocompatibility Antigens Class I
  • IP10-Mig receptor
  • Interleukin-1beta
  • Receptors, Cytokine
  • Socs1 protein, mouse
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • fas Receptor
  • Interferon-gamma
  • Receptor-Interacting Protein Serine-Threonine Kinases