Clarification of the mechanisms for connective tissue destruction and alveolar bone resorption in periodontal disease by comprehensive analysis of infiltrating T cells using immunological and molecular biological techniques

利用免疫学和分子生物学技术对浸润性 T 细胞进行综合分析，阐明牙周病中结缔组织破坏和牙槽骨吸收的机制

基本信息

批准号：
16390613
负责人：
YAMAZAKI Kazuhisa
金额：
$ 9.09万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390613/
关键词：
Regulatory T cells FOXP3 T-cell clone Periodontitis 炎症性サイトカイン抗炎症性サイトカイン mRNA

项目摘要

Periodontitis lesion is characterized by connective tissue destruction and alveolar bone resorption. The lesion contains large numbers of B lymphocytes and plasma cells together with significant numbers of T lymphocytes. We have previously found that the some of the T-cells in the lesion recognize auto-antigens such as heat-shock protein 60 and the response to such antigens play important roles in the pathogenesis of periodontitis. T-cell population can be classified into several distinct subsets functionally as well as phenotypically. In order to elucidate the role of various T-cell subsets in the pathogenesis of periodontal diseases, we comprehensively analyzed the periodontitis lesion-infiltrating T cells using immunological and molecular biological techniques.The results demonstrated that a fraction of CD4^+ T cells expressed both CTLA-4 and CD25. CD4^+CD25^+CTLA-4^+ T cells are thought to be characteristic of natural regulatory T cells (Tr) and the percentage of CD4^+CD25^+ Tr cel … More ls increased with increasing proportions of B-cells relative to T-cells in periodontitis. Gene expression analysis showed that FOXP3, a characteristic marker for CD4^+CD25^+ Tr cells, TGF-β1 and IL-10 were expressed higher in periodontitis than gingivitis. Furthermore, it is demonstrated that another regulatory T cells called NKT cells which has been implicated in periodontitis are activated by CD Id-restricted manner and this NKT cell activation may mediate suppression of auto-reactive T cells.In order to further analyze the role of T cells in the lesion, we established T-cell clones from the gingival tissues of periodontitis patients and examined the effecter function and their gene expression. Most but not all the T-cell clones from gingival tissues expressed mRNA for IFN-γ, IL-4, CD25 and CTLA-4. The frequency of T-cell clones expressing FOXP3 was very high. However, expressions of genes for IL-17 and RANKL, both of which are involved in the bone resorption, were variable among the T-cell clones.Clonal analysis of the T cells clearly demonstrated the presence of T-cell populations reactive to human HSP60 and P. gingivalis GroEL in the peripheral circulation of atherosclerosis patients. These T-cells had been detected in the gingival tissues of periodontitis patients. Furthermore, these HSP60-reactive T cells seemed to be present in atherosclerotic lesions in some patients.In conclusion, periodontitis lesion-infiltrating T cells may be involved in the pathogenesis of not only periodontal diseases but also atherosclerosis. Less

牙周炎病变的特征是结缔组织破坏和Alloolar骨骼分辨率。病变含有大量的B淋巴细胞和浆细胞以及大量的T淋巴细胞。我们以前已经发现，病变中的某些T细胞识别自动抗原（例如热冲蛋白60），对此类抗原的反应在牙周炎发病机理中起着重要作用。 T细胞种群可以在功能和表型上分类为几个不同的子集。为了阐明各种T细胞亚群在牙周疾病的发病机理中的作用，我们使用免疫学和分子生物学技术彻底分析了牙周炎病变渗透的T细胞。结果表明，CD4^+ T细胞的一部分表达了CTLA-4和CD25。 CD4^+CD25^+CTLA-4^+T细胞被认为是天然调节T细胞（TR）的特征，并且CD4^+CD25^+Tr cel的百分比相对于牙周炎中的T细胞而增加。基因表达分析表明，FOXP3是CD4^+ CD25^+ TR细胞，TGF-β1和IL-10的特征标记，在牙周炎中比牙龈炎高。 Furthermore, it is demonstrated that another regulatory T cells called NKT cells which has been implemented in periodontitis are activated by CD Id-restricted manner and this NKT cell activation may mediate suppression of auto-reactive T cells.In order to further analyze the role of T cells in the lesion, we established T-cell clones from the gingival tissues of periodontitis patients and examined the effecter function and their gene expression.大多数但不是所有来自牙龈组织的T细胞克隆都表达了IFN-γ，IL-4，CD25和CTLA-4的mRNA。表达FOXP3的T细胞克隆的频率很高。然而，IL-17和RANKL的基因表达在骨骼分辨率中都涉及骨骼。在T细胞克隆中，T细胞的循环分析清楚地表明，在动脉粥样硬化患者的外围循环中，T细胞对人HSP60和人类HSP60和牙龈疟原虫的反应。这些T细胞在牙周炎患者的牙龈组织中检测到。此外，在某些患者的动脉粥样硬化病变中，这些HSP60反应性T细胞似乎存在于动脉粥样硬化病变中。总而言，牙周炎病变浸润的T细胞可能不仅参与牙周疾病的发病机理，而且还参与动脉粥样硬化的发病机理。较少的