Martin S, Hibino T, Faust A, Kleemann R, Kolb H
Diabetes Research Institute, Heinrich-Heine-University, Düsseldorf, Germany.
J Autoimmun. 1996 Oct;9(5):637-43. doi: 10.1006/jaut.1996.0083.
The infiltration of pancreatic islets by mononuclear cells is the hallmark of the development of insulin dependent diabetes mellitus (IDDM) in the NOD mouse, an animal model for human IDDM. The aim, of this study was to correlate adhesion molecule expression with the degree of islet infiltration and to compare Th1- and Th2-driven islet inflammation. Cryostat sections of NOD mouse pancreata before and after diabetes development were analysed by semiquantitative immunohistochemistry. NOD mouse islets did not show the expression of ICAM-1, LFA-1, L-selectin and VCAM-1 prior to infiltration by mononuclear cells. Furthermore, islets with early stage insulitis (grade 1, periinsular location of small infiltrates) still were devoid of adhesion molecule expression. ICAM-1 and LFA-1 were first demonstrable in islets with strong periinsular infiltrates (insulitis grade 2) while L-selectin and VCAM-1 were only seen in islets with mild or strong intraislet infiltration (grade 3-4). Adhesion molecules were demonstrable in areas of macrophage and T-lymphocyte infiltrates but not in adjacent endocrine islet tissue. Islets of all infiltration stages contained Th2 lymphocytes (positive for IL-4). Substantial numbers of Th1 cells (positive for IFN-gamma, TNF-alpha, IL-2 and/or IL-2 receptor) were observed only after acceleration of diabetes development by a single injection of cyclophosphamide (250 mg/kg i.p.). Interestingly, the adhesion molecule expression pattern in islets with "Th1' versus "Th2 insulitis' was not different. In conclusion, the expression of adhesion molecules in islets during the development of autoimmune diabetes does not precede mononuclear infiltration but probably occurs in response to the activation of initial small infiltrates. ICAM-1 and LFA-1 expression is seen prior to L-selectin and VCAM-1. However, adhesion molecule expression during Th1 versus Th2 cell infiltration is very similar, suggesting similar adhesion molecule requirements of the two Th subsets.
胰岛被单核细胞浸润是NOD小鼠（一种人类胰岛素依赖型糖尿病（IDDM）的动物模型）发生IDDM的标志。本研究的目的是将黏附分子表达与胰岛浸润程度相关联，并比较Th1和Th2驱动的胰岛炎症。通过半定量免疫组织化学分析糖尿病发生前后NOD小鼠胰腺的冰冻切片。在单核细胞浸润之前，NOD小鼠胰岛未显示ICAM-1、LFA-1、L-选择素和VCAM-1的表达。此外，处于早期胰岛炎（1级，小浸润灶位于胰岛周围）的胰岛仍无黏附分子表达。ICAM-1和LFA-1首先在胰岛周围有强烈浸润（胰岛炎2级）的胰岛中被检测到，而L-选择素和VCAM-1仅在有轻度或强烈胰岛内浸润（3-4级）的胰岛中可见。黏附分子在巨噬细胞和T淋巴细胞浸润区域可检测到，但在相邻的内分泌胰岛组织中未检测到。所有浸润阶段的胰岛均含有Th2淋巴细胞（IL-4阳性）。仅在单次注射环磷酰胺（250 mg/kg腹腔注射）加速糖尿病发展后，才观察到大量Th1细胞（IFN-γ、TNF-α、IL-2和/或IL-2受体阳性）。有趣的是，“Th1”与“Th2胰岛炎”的胰岛中黏附分子表达模式并无差异。总之，自身免疫性糖尿病发展过程中胰岛黏附分子的表达并非先于单核细胞浸润，而是可能在初始小浸润灶激活后发生。ICAM-1和LFA-1的表达先于L-选择素和VCAM-1。然而，Th1与Th2细胞浸润期间黏附分子的表达非常相似，提示这两个Th亚群对黏附分子的需求相似。
