Project/Area Number |
03404056
|
Research Category |
Grant-in-Aid for General Scientific Research (A)
|
Allocation Type | Single-year Grants |
Research Field |
Conservative dentistry
|
Research Institution | Osaka University |
Principal Investigator |
OKADA Hiroshi Osaka University Faculty of Dentistry, Professor, 歯学部, 教授 (40038865)
|
Co-Investigator(Kenkyū-buntansha) |
KUSUMOTO Yutaka Osaka University Faculty of Dentistry, Instructor, 歯学部, 助手 (40252689)
SHIMABUKURO Yoshio Osaka University Faculty of Dentistry, Istructor, 歯学部, 助手 (50231361)
MURAKAMI Shinya Osaka University Faculty of Dentistry, Assistant Professor, 歯学部・附属病院, 講師 (70239490)
SHIMAUCHI Hidetoshi Osaka University Faculty of Dentistry, Assistant Professor, 歯学部・附属病院, 講師 (70187425)
MIKI Yasuo Osaka University Faculty of Dentistry, Associate Professor, 歯学部, 助教授 (80165993)
伊藤 博夫 大阪大学, 歯学部, 助手 (40213079)
原田 泰 大阪大学, 歯学部附属病院, 助手 (10181025)
木村 重信 大阪大学, 歯学部附属病院, 講師 (10177917)
|
Project Period (FY) |
1991 – 1993
|
Project Status |
Completed (Fiscal Year 1993)
|
Budget Amount *help |
¥31,800,000 (Direct Cost: ¥31,800,000)
Fiscal Year 1993: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1992: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1991: ¥22,300,000 (Direct Cost: ¥22,300,000)
|
Keywords | periodontal disease / T cells / Autologous mixed lymphocyte reaction / CD45R / cell adhesion molecule / gingival fibroblast / VLA integrin / CD44 / T細胞クローン / インテグリン / 自己反応性T細胞 / 歯周炎 / 多クロ-ン性B細胞活性化 |
Research Abstract |
Based on the responsiveness of autologous mixed-lymphocyte reactions (AMLR) of peripheral blood lymphocytes (PBL), we categorized periodontitis patients into two groups (low-AMLR patients and normal AMLR patients). Flow cytometric analyzes revealed a lower percentage of CD45RA^+ cells in CD4^+ cells (CD4^+CD45RA^+ T cells) in the low-AMLR patients than those in normal-AMLR patients. However, the percentage of CD4^+ CD45RO^+ T cells was not statistically different between the groups. In contrast, T cells infiltrated into chronically inflamed gingiva demonstrated a higher percentage of CD4^+CD45RO^+ T cells than PBL in those patients, suggesting that activated T cells selectively migrated into periodontal lesions. We then examined molecular basis of the adherence between T cells and human gingival fibroblasts (HGF) to reveal the mechanisms of T cell retention in diseased sites. Blocking experiments utilizing monoclonal antibodies specific for cell adhesion molecules revealed that VLA inte
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grins and CD44 molecules were involved in this heterotypic cell-cell interaction. Furthermore, it was also demonstrated that stimulation with IL-1beta, TNF-alpha or IFNgamma increased the binding abilities of HGF to activated T cells and that LFA-1/ICAM-1 pathway playd central roles in those situations. Furthermore, it was also demonstrated that IFNgamma-treated HGF regulated T-cell proliferative responses. We then examined the responsiveness of PBL from periodontitis patients to periodontopathic bacteria. PBL from periodontitis patients were assessed the proliferative responses to Porphyromonas gingivalis (P.g) fimbriae in vitro and were subjected to the establishment of T cell lines and their clones. PBL from the patients with high level of fimbriae-specific antibodies significantly proliferated to the fimbriae, suggesting that fimbriae-specific T cells were present in the peripheral blood of periodontitis patients. These fimbriae-specific T cells may recruit to the periodontal lesions and play important roles in local immunomodulation. Less
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