Dominant role of intercellular adhesion molecule-1 in the pathogenesis of autoimmune diabetes in non-obese diabetic mice

J Autoimmun. 2001 Sep;17(2):109-17. doi: 10.1006/jaut.2001.0526.


Intercellular adhesion molecule (ICAM)-1 is involved in forming the immunological synapse. The contribution of ICAM-1 to immune responses is not critical because mice with a disrupted ICAM-1 gene do not have grossly abnormal immune reactivity. Here we report on the surprising finding that diabetes-prone NOD mice with a disrupted ICAM-1 gene (ICAM-1(-/-)) are completely protected from disease development. While 64% of ICAM-1(+/+) and 44% of ICAM-1(+/-) female NOD mice developed overt diabetes until 310 days old, no ICAM-1(-/-) NOD mice became hyperglycaemic. Histological examinations revealed minor infiltration around pancreatic islets of ICAM1(-/-) NOD mice. Administration of cyclophosphamide caused a progression to severe islet destruction in ICAM-1(+/+) NOD mice within 10 days. In contrast, ICAM-1(-/-) mice showed only mild insulitis. Furthermore, ICAM-1(+/+) NOD mice showed an increase of IFN-gamma, interleukin (IL)-12p40 and IL-12p35 pancreatic mRNA levels, leading to an increased ratio of IFN-gamma: IL-4 and IL-12p40: IL-12p35 expression. In contrast, ICAM-1(-/-) NOD mice did not upregulate IFN-gamma or IL-12p40 gene expression but maintained IL-4 and increased IL-12p35 gene expression. These results identify a dominant and non-redundant role of ICAM-1 in the development of autoimmune diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Crosses, Genetic
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / prevention & control
  • Female
  • Inflammation / immunology
  • Inflammation / prevention & control
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / physiology*
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • T-Lymphocyte Subsets / immunology
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Intercellular Adhesion Molecule-1