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

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.

Martin S ，van den Engel NK ，Vinke A ，Heidenthal E ，Schulte B ，Kolb H ... -  《JOURNAL OF AUTOIMMUNITY》

Differential expression of ICAM-1 and LFA-1 versus L-selectin and VCAM-1 in autoimmune insulitis of NOD mice and association with both Th1- and Th2-type infiltrates.

Martin S ，Hibino T ，Faust A ，Kleemann R ，Kolb H ... -  《JOURNAL OF AUTOIMMUNITY》

IFN-gamma gene expression in pancreatic islet-infiltrating mononuclear cells correlates with autoimmune diabetes in nonobese diabetic mice.

Rabinovitch A ，Suarez-Pinzon WL ，Sorensen O ，Bleackley RC ，Power RF ... -  《JOURNAL OF IMMUNOLOGY》

Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway.

Moriyama H ，Yokono K ，Amano K ，Nagata M ，Hasegawa Y ，Okamoto N ，Tsukamoto K ，Miki M ，Yoneda R ，Yagi N ，Tominaga Y ，Kikutani H ，Hioki K ，Okumura K ，Yagita H ，Kasuga M ... -  《JOURNAL OF IMMUNOLOGY》

Suppression of cyclophosphamide induced diabetes development and pancreatic Th1 reactivity in NOD mice treated with the interleukin (IL)-12 antagonist IL-12(p40)2.

Rothe H ，O'Hara RM Jr ，Martin S ，Kolb H ... -  《DIABETOLOGIA》