PREVENTION OF AUTOIMMUNE INSULIN-DEPENDENT DIABETES IN NONOBESE DIABETIC MICE BY ANTI-LFA-1 AND ANTI-ICAM-1 MAB
PREVENTION OF AUTOIMMUNE INSULIN-DEPENDENT DIABETES IN NONOBESE DIABETIC MICE BY ANTI-LFA-1 AND ANTI-ICAM-1 MAB
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DOI：
10.1093/intimm/6.6.831
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发表时间：
1994-06-01
影响因子：
4.4
通讯作者：
KASUGA, M
中科院分区：
文献类型：
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作者：
HASEGAWA, Y;YOKONO, K;KASUGA, M
多种粘附分子参与许多重要的免疫反应，因此可能与多种自身免疫性疾病的发病机制有关。然而，几乎没有证据表明这些分子在自身免疫性胰岛素依赖型糖尿病中的作用。在这里，我们提出了几条线的证据表明，白细胞功能相关抗原-1（LFA-1）和它的反受体细胞间粘附分子（ICAM-1），这些粘附分子中最重要的一对，参与了自身免疫性糖尿病的发展在非肥胖糖尿病（NOD）小鼠。免疫组化显示NOD胰腺中胰岛浸润的单个核细胞和血管内皮细胞ICAM-1呈高表达。从5至30（或12）周龄体内给予抗LFA-1或抗ICAM-1 mAb对自发性糖尿病的发展具有非常强的预防作用，胰岛炎显著减少，而两种抗体，即使同时联合使用，也不能预防环磷酰胺诱导的糖尿病。胰岛炎和糖尿病的连续转移到年轻的NOD小鼠注射胰岛来源的单核细胞从糖尿病供体被完全阻断了两种抗体给收件人。因此，本研究提供了第一个证据，即免疫干预LFA-1-ICAM-1相互作用对NOD小鼠的自身免疫性糖尿病具有很强的预防作用。
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 antigen-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. Immunohistochemical study showed the hyperexpression of ICAM-1 on islet-infiltrating mononuclear cells and vascular endothelium in NOD pancreas. In vivo administration of anti-LFA-1 or anti-ICAM-1 mAb from 5 to 30 (or 12) weeks of age exerted a very strong preventative 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-induced 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 immunointervention to LFA-1-ICAM-1 interaction has a strong prophylactic effect on autoimmune diabetes in NOD mice.