New Concept of Antigen Presentation by Gingival Epithelial Cells in Periodontal Disease.

牙周病中牙龈上皮细胞抗原呈递的新概念。

• 批准号: 14370712
• 负责人: IZUMI Yuichi
• 金额: $ 8.64万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370712/
• 关键词: periodontal disease; gingival epithelial cells; CD4^+T cells; MHC class II; CTLA4-Ig; B7-1; RANKL; 破骨細胞分化因子; 破骨細胞; T細胞性免疫反応

The purpose of the present research project was to clarify the new concept of antigen presentation by gingival epithelial cells in periodontal disease. HLA-DR (major histocompatibility complex [MHC] class II) is often expressed by epithelial cells in gingival tissues with periodontal disease but not by cells in healthy gingival tissues. Confocal microscopic analyses revealed that gingival epithelial cells(GEC) from tissue with periodontal disease express both HLA-DR and B7-1(CD80) costimulatory molecules. Rat GEC lines were established to elucidate the possible role of MHC class II and B7-1 expression by GEC. Stimulation of a rat GEC line with gamma interferon (IFN-γ) induced the expression of MHC class II, whereas the cell line constitutively expressed B7-1 costimulatory molecules as determined by reverse transcription-PCR and flow cytometry. Actinobacillus actinomycetemcomitans Omp29-specific CD4^+ Th1 clone cells proliferated in response to pretreatment of GEC with fixed A.actinomycetemcomitans and IFN-γ. However, the Th1 cells did not respond to pretreatment of GEC with the bacteria alone or IFN-γalone. The activation of Th1 clone cells induced by the GEC was inhibited by antibody to MHC class II or by CTLA4 immunoglobulin(CTLA4-Ig). Lymph node T cells did not demonstrate superantigen activity to A.actinomycetemcomitans, although both lymph node T cells and Th1 clone cells were sensitive to superantigen activity of staphylococcal enterotoxin A as cultured in the presence of IFN-γ-treated GEC. These results suggested that GEC can take up bacterial antigen and consequently process and present the bacterial antigen to CD4^+ T cells by MHC class II in conjunction with B7 costimulation. GEC appeared to play a role in the adaptive immune response by stimulating antigen-specific CD4^+ T cells.

本研究旨在阐明牙周病中牙龈上皮细胞抗原提呈的新概念。HLA-DR（major histocompatibility complex [MHC] class II）常在牙周病牙龈组织上皮细胞表达，而在健康牙龈组织中不表达。共聚焦显微镜分析显示，牙龈上皮细胞（GEC）从牙周病组织表达HLA-DR和B7-1（CD 80）共刺激分子。建立大鼠GEC系以阐明GEC表达MHC II类和B7-1的可能作用。用γ-干扰素（IFN-γ）刺激大鼠GEC细胞系可诱导MHC II类分子的表达，而逆转录-PCR和流式细胞术测定细胞系组成型表达B7-1共刺激分子。伴放线放线杆菌Omp 29特异性CD 4 ^+ Th 1克隆细胞对用固定的伴放线放线杆菌和IFN-γ预处理GEC产生增殖反应。然而，Th 1细胞对单独用细菌或单独用IFN-γ预处理GEC没有应答。GEC诱导的Th 1克隆细胞的活化可被抗MHC II类抗体或CTLA 4免疫球蛋白（CTLA 4-IG）抑制。淋巴结T细胞对伴放线杆菌没有表现出超抗原活性，尽管淋巴结T细胞和Th 1克隆细胞在IFN-γ处理的GEC存在下培养时对葡萄球菌肠毒素A的超抗原活性敏感。这些结果表明，GEC可以摄取细菌抗原，并通过MHC Ⅱ类分子和B7共刺激作用，将细菌抗原加工并呈递给CD 4 ^+ T细胞。GEC似乎通过刺激抗原特异性CD 4 ^+ T细胞在获得性免疫应答中发挥作用。

项目成果

Statins reduce inflammation in periodontal diseases.

他汀类药物可减少牙周疾病的炎症。

• 发表时间: 2005
• 期刊: Journal of Clinical and Experimental Medicine 212
• 作者: Tan;J.K.;Yamaguchi;I.;Ishikawa;S.;Naito;T.;Yokota;M.;Matsuo Yamamoto
• 通讯作者: Matsuo Yamamoto

Expression of major histocompatibility complex class II and CD80 by gingival epithelial cells induces activation of CD4+ T cells in response to bacterial challenge

• DOI: 10.1128/iai.73.2.1044-1051.2005
• 发表时间: 2005-02-01
• 期刊: INFECTION AND IMMUNITY
• 影响因子: 3.1
• 作者: Matsuyama, T;Kawai, T;Taubman, MA
• 通讯作者: Taubman, MA

Statins reduce inflammation in periodontal diseases

他汀类药物可减少牙周疾病的炎症

• 发表时间: 2005
• 期刊: Journal of Clinical and Experimental Medicine 212・9
• 作者: Tan;J.K.;Yamaguchi;I.;Ishikawa;S.;Naito;T.;Yokota;M.;Matsuo Yamamoto
• 通讯作者: Matsuo Yamamoto

Changes of α1-protease inhibitor and secretory leukocyte protease inhibitor levels in gingival crevicular fluid before and after non-surgical periodontal treatment

• DOI: 10.1034/j.1601-0825.2003.02884.x
• 发表时间: 2003-09-01
• 期刊: ORAL DISEASES
• 影响因子: 3.8
• 作者: Nakamura-Minami, M;Furuichi, Y;Izumi, Y
• 通讯作者: Izumi, Y

Expression of CD14, CD16 and CD45RA on monocytes from periodontitis patients

• DOI: 10.1111/j.1600-0765.2004.00713.x
• 发表时间: 2004-02-01
• 期刊: JOURNAL OF PERIODONTAL RESEARCH
• 影响因子: 3.5
• 作者: Nagasawa, T;Kobayashi, H;Izumi, Y
• 通讯作者: Izumi, Y