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

Diverse adhesion molecules participate in many important responsesand thus would be implicated in the pathogenesis of variousautoimmune diseases. However, there is little evidence for therole of these molecules in autoimmune insulin-dependent diabetesmellitus. Here we present several lines of evidence suggestingthat leukocyte function-associated antlgen-1 (LFA-1) and itscounter-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 thenon-obese diabetic (NOD) mouse. Immunohlstochemlcal study showedthe hyperexpresslon of ICAM-1 on islet-lnflltratlng mononuclearcells and vascular endothellum in NOD pancreas. In vivo administrationof antl-LFA-1 or antl-ICAM-1 mAb from 5 to 30 (or 12) weeksof age exerted a very strong preventatlve effect on the developmentof spontaneous diabetes with a marked reduction of insulitis,whereas both antibodies, even combined to use simultaneously,could not prevent cyclophosphamide-lnduced diabetes. Adoptivetransfer of insulitis and diabetes to young NOD mice followingthe injection of islet-derived mononuclear cells from diabeticdonors was completely blocked by administration of both antibodiesto recipients. The present study, therefore, provides the firstevidence that immunolnterventlon to LFA-1 - ICAM-1 Interactionhas a strong prophylactic effect on autoimmune diabetes in NODmice.