Phenotypic and functional alteration of regulatory T cells in the peripheral blood of patients with silicosis
| Project/Area Number |
16590491
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
HYODOH Fuminori Kawasaki Medical School, Medicine, Lecturer, 医学部, 講師 (80069070)
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| Co-Investigator(Kenkyū-buntansha) |
OTSUKI Takemi Kawasaki Medical School, Medicine, Professor, 医学部, 教授 (40160551)
MIURA Yoshie Kawasaki Medical School, Medicine, Assistant, 医学部, 助手 (00388935)
NISHIMURA Yasumitsu Kawasaki Medical School, Medicine, Lecturer, 医学部, 講師 (90360271)
高田 晶子 川崎医科大学, 医学部, 助手 (30278957)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | immunological disorder / silicosis / autoantibody / autoimmune disease / CD4+CD25+ regulatory T cell / CD4+CD25-T cell / FOXP3 / suppressive effect / 自己抗体 / 自己免疫疾患 / 制御性T細胞 / 末梢血単核細胞 |
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| Research Abstract |
To explore the mechanisms involved in immunological disorders associated with silicosis, such as the appearance of autoantibodies and the complications of autoimmune disease, we investigated the quality and quantity of CD4+CD25+ regulatory T cells in silicosis patients and compared them with those of healthy donors. Peripheral blood mononuclear cells (PBMC) from 57 silicosis patients and 50 healthy donors were analyzed for the frequency of Treg. Treg and CD4+CD25-T cells (Tneg) from five healthy donors and five silicosis patients sorted by flow cytometer were used for a functional assay of Treg and to obtain the gene expression pattern for FOXP3, a Treg specific gene, CTLA-4, a regulator gene for the suppressive function of Treg and two activation-related genes, CD122 and CD132. Although actual Treg frequency in the silicosis patients did not differ from that in the healthy donors, Treg frequency in the silicosis patients lost correlation with age and was reduced when compared with age-corrected levels calculated from the data of healthy donors. The suppressive effect of Treg from silicosis patients on Tneg activation by allogenic PBMC was decreased when the Treg : Tneg ratio was 1:1/4 to 1/2. In addition, the Treg dominancy of FOXP3 and CTLA-4 expression and the Tneg dominancy of CD132 expression found in healthy donors were lost in silicosis patients. Furthermore, we demonstrated that pure silica activates the PBMC from healthy donors in vitro, by monitoring CD69 expression. These findings indicated that chronically activated T cells may take the place of the Treg fraction in silicosis patients due to recurrent exposure to silica, and this results in a reduction of Treg frequency and function.
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Report
(3 results)
Research Products
(20 results)
