Possible Role of Gingival Epithelial Cells in Host Immune Response of Periodontal Disease Progression

牙龈上皮细胞在牙周病进展的宿主免疫反应中的可能作用

基本信息

批准号：
12672038
负责人：
IZUMI Yuichi
金额：
$ 2.18万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672038/
关键词：
perodontal disease gingival epithelial cells immune response CD 80 CD 86 MHC class II prostaglandin cyclooxygenase-2 免疫応答

项目摘要

The purpose of the present research project was to clarify the possible role of gingival epithelial cells in host immune response of periodontal disease progression. Antigen presented by professional antigen-presenting cells (APC), which express both MHC class II and B7 costimulatory molecules, results in CD4+ T cell activation. In contrast, antigen presentation by MHC class II expressing non-professional APC which lack costimulatory molecules can render CD4+ T cells into a state of nonresponsiveness. In general, B7 costimulatory molecules are expressed by professional APC, such as macrophages or dendritic cells. Expression of MHC class II and B7-1 was detected on periodontal diseased human gingival epithelial tissue in situ by double color exposure confocal microscopy, but not in healthy gingival tissue. Also, two lines of rat gingival epithelial cells (GEC) demonstrated to constitutively expressed B7-1, but not B7-2 as analyzed by flow cytometry. By contrast, expression of MHC class II was only detected on both rat GEC klines after IFN-γ stimulation. Other rat non-professional APC such as endothelial cells or fibroblasts did not express B7-1 even after stimulation with IFN-γ. In order to elucidate the immunological significance of this ectopic B7-1 expression, antigen (Actinobacillus actinomycetemcomitans)-spedfic CD4+ Th1 T cell clones were cocultured with IFN-γ-/antigen-treated rat GEC. Consequently, the T cells became unresponsive to subsequent antigen-stimulation by professional APC as demonstrated by diminished proliferation. The induction of unresponsiveness was inhibited by anti-class II mAb or anti-CD80 mAb in the coculture of T clone cells and IFN-γ/antigen-treated GEC suggesting that GEC apparently present bacterial antigen, which resulted in T cell down regulation. These results suggest that ectopic expression of B7-1 by GEC may play a regulatory T cell to the commensal bacteria in the oral cavity in the context of a local inflammatory response.

本研究项目的目的是阐明牙龈上皮细胞在牙周病进展的宿主免疫反应中的可能作用，该抗原由表达 MHC II 类和 B7 共刺激分子的专业抗原呈递细胞 (APC) 呈递。相反，表达 MHC II 类缺乏共刺激分子的非专业 APC 的抗原呈递可以使 CD4+ T 细胞进入无反应状态。 B7 共刺激分子由专业 APC 表达，例如巨噬细胞或树突状细胞。通过双色曝光共聚焦显微镜在牙周病人类牙龈上皮组织中原位检测到 MHC II 类和 B7-1 的表达，但在健康牙龈组织中未检测到。此外，根据流式分析，大鼠牙龈上皮细胞 (GEC) 的两系显示组成型表达 B7-1，但不表达 B7-2相比之下，仅在 IFN-γ 刺激后在两种大鼠 GEC 细胞系上检测到 MHC II 类表达，而其他大鼠非专业 APC（例如内皮细胞或成纤维细胞）即使在用 IFN-γ 刺激后也不表达 B7-1。为了阐明这种异位 B7-1 表达的免疫学意义，抗原 (Actinobacillus actinomycetemcomitans) 特异性 CD4+ Th1 T 细胞克隆与经 IFN-γ-/抗原处理的大鼠 GEC 共培养，T 细胞对专业 APC 的后续抗原刺激变得无反应，如抗 II 类单克隆抗体或抗-II 类单克隆抗体抑制了无反应的诱导。 T 克隆细胞和 IFN-γ/抗原处理的 GEC 共培养物中的 CD80 mAb 表明 GEC 明显呈递细菌抗原，从而导致 T 细胞下调。 GEC 异位表达 B7-1 可能在局部炎症反应中对口腔共生细菌发挥调节性 T 细胞作用。