Details

Autor(en) / Beteiligte

• Hasegawa, Yutaka
• Yokono, Koichi
• Taki, Toshiya
• Amano, Kazuhiko
• Tominaga, Yoichi
• Yoneda, Ryoji
• Yagi, Norio
• Maeda, Sakan
• Yagita, Hideo
• Okumura, Ko
• Kasuga, Masato

Titel

Prevention of autoimmune insulin-dependent diabetes in non-obese diabetic mice by anti-LFA-1 and anti-ICAM-1 mAb

Ist Teil von

• International immunology, 1994-06, Vol.6 (6), p.831-838

Ort / Verlag

Oxford: Oxford University Press

Erscheinungsjahr

1994

Quelle

MEDLINE

Beschreibungen/Notizen

• Diverse adhesion molecules participate in many important responses and thus would be implicated in the pathogenesis of various autoimmune diseases. However, there is little evidence for the role of these molecules in autoimmune insulin-dependent diabetes mellitus. Here we present several lines of evidence suggesting that leukocyte function-associated antlgen-1 (LFA-1) and its counter-receptor intercellular adhesion molecules (ICAM-1), one of the most important pairs among these adhesion molecules, are involved in the development of autoimmune diabetes in the non-obese diabetic (NOD) mouse. Immunohlstochemlcal study showed the hyperexpresslon of ICAM-1 on islet-lnflltratlng mononuclear cells and vascular endothellum in NOD pancreas. In vivo administration of antl-LFA-1 or antl-ICAM-1 mAb from 5 to 30 (or 12) weeks of age exerted a very strong preventatlve effect on the development of spontaneous diabetes with a marked reduction of insulitis, whereas both antibodies, even combined to use simultaneously, could not prevent cyclophosphamide-lnduced diabetes. Adoptive transfer of insulitis and diabetes to young NOD mice following the injection of islet-derived mononuclear cells from diabetic donors was completely blocked by administration of both antibodies to recipients. The present study, therefore, provides the first evidence that immunolnterventlon to LFA-1 - ICAM-1 Interaction has a strong prophylactic effect on autoimmune diabetes in NOD mice.