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

牙周炎的病变以结缔组织破坏和牙槽骨吸收为特征。病变包含大量的B淋巴细胞和浆细胞以及大量的T淋巴细胞。我们以前发现，病变中的一些T细胞识别自身抗原，如热休克蛋白60，对这些抗原的反应在牙周炎的发病机制中起重要作用。T细胞群可以在功能上以及表型上分为几个不同的亚群。为了阐明不同T细胞亚群在牙周病发病中的作用，我们采用免疫学和分子生物学技术对牙周炎病变浸润的T细胞进行了全面分析，结果表明，一部分CD 4 ^+ T细胞同时表达CTLA-4和CD 25。CD 4 ^+ CD 25 ^+CTLA-4^+ T细胞被认为是天然调节性T细胞（Tr）的特征， ...更多信息 LS随着牙周炎中B细胞相对于T细胞比例的增加而增加。基因表达分析显示，牙周炎组织中FOXP 3（CD 4 ^+ CD 25 ^+ Tr细胞的特征性标志物）、TGF-β1和IL-10的表达高于牙龈炎组织。此外，还发现与牙周炎有关的另一种调节性T细胞NKT细胞通过CD Id限制性方式被激活，这种NKT细胞的激活可能介导了自身反应性T细胞的抑制。为了进一步分析T细胞在牙周炎病变中的作用，我们从牙周炎患者牙龈组织中建立了T细胞克隆，并检测了其效应功能及其基因表达。来自牙龈组织的大多数但不是所有的T细胞克隆表达IFN-γ、IL-4、CD 25和CTLA-4的mRNA。表达FOXP 3的T细胞克隆的频率非常高。然而，IL-17和RANKL的基因表达，这两者都参与骨吸收，是可变的T细胞克隆中的T细胞克隆分析清楚地表明，在动脉粥样硬化患者的外周循环中的T细胞群反应的人HSP 60和牙龈卟啉单胞菌GroEL的存在。在牙周炎患者的牙龈组织中检测到这些T细胞。此外，这些HSP 60反应性T细胞似乎存在于动脉粥样硬化病变的一些患者。总之，牙周炎病变浸润的T细胞可能参与牙周疾病的发病机制，但动脉粥样硬化。少

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