Department of Morphological Biology, Pathology Section, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka, Japan.
Histol Histopathol. 2011 Jun;26(6):725-33. doi: 10.14670/HH-26.725.
To elucidate the involvement of intercellular adhesion molecule-1 (ICAM-1) in the migration of lymphocytes to the oral mucosal epithelium in a rat model of acute graft-versus-host disease (AGVHD), we investigated (1) ICAM-1 and major histocompatibility complex (MHC) class II expression by keratinocytes (KCs) and their role in the epithelial infiltration of CD8+ cells, (2) the tissue expression of interferon-γ (IFN-γ) mRNA and expression of IFN-γ receptor by KCs, and (3) the ability of KCs to direct CD8+ cells into the epithelial layers. We classified the oral mucosal lesions into three consecutive temporal phases on the basis of increased epithelial ICAM-1 expression: basal- (phase I), parabasal- (phase II), and pan-epithelial except for the cornified cell layer (phase III). Basal ICAM-1 expression by KCs preceded that of MHC class II molecules, infiltration of CD8+ cells and epithelial histological changes. Tissue expression of IFN-γ mRNA and expression of IFN-γ receptor on KCs evidenced by immunohistochemistry were detected in early lesions (phase I), indicating that locally produced IFN-γ induced ICAM-1 expression by KCs. CD8+ cells were bound to KCs in frozen sections of epithelial lesions, whereas no lymphocyte attachment was observed in normal KC. Adherence could be inhibited by pretreating CD8+ cells with lymphocyte function-associated antigen-1 (LFA-1) antibody and/or by pretreating sections with ICAM-1 antibody. Our data suggest that in the early phase of acute oral mucosal GVHD, the induction of ICAM-1 expression on KCs leads to the migration of CD8+ cells into the epithelium and that this is mediated in part by the ICAM-1/LFA-1 pathway.
为了阐明细胞间黏附分子-1（ICAM-1）在大鼠移植物抗宿主病（AGVHD）模型中淋巴细胞向口腔黏膜上皮迁移中的作用，我们研究了（1）角蛋白细胞（KC）中 ICAM-1 和主要组织相容性复合物（MHC）Ⅱ类的表达及其在 CD8+细胞上皮浸润中的作用，（2）干扰素-γ（IFN-γ）mRNA 的组织表达和 KC 中 IFN-γ受体的表达，以及（3）KC 引导 CD8+细胞进入上皮层的能力。我们根据上皮细胞 ICAM-1 表达的增加将口腔黏膜病变分为三个连续的时间阶段：基底（I 期）、副基底（II 期）和除角化细胞层外的全上皮（III 期）。KC 中 ICAM-1 的表达先于 MHC Ⅱ类分子、CD8+细胞浸润和上皮组织学改变。通过免疫组织化学检测到早期病变（I 期）中 KC 上 IFN-γ mRNA 的组织表达和 IFN-γ受体的表达，表明局部产生的 IFN-γ诱导 KC 中 ICAM-1 的表达。在冰冻切片上皮病变中，CD8+细胞与 KC 结合，而在正常 KC 中未观察到淋巴细胞附着。用淋巴细胞功能相关抗原-1（LFA-1）抗体预处理 CD8+细胞和/或用 ICAM-1 抗体预处理切片可抑制粘附。我们的数据表明，在急性口腔黏膜 GVHD 的早期阶段，KC 上 ICAM-1 表达的诱导导致 CD8+细胞向上皮迁移，部分通过 ICAM-1/LFA-1 途径介导。
