| Project/Area Number |
10670411
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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 |
内科学一般
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| Research Institution | Okayama University |
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Principal Investigator |
YAMAMURA Masahiro Okayama University Medical School, Assistant Professor, 医学部, 助教授 (80252956)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Seishi Okayama University Medical School, Assistant, 医学部・附属病院, 助手 (70294452)
HASHIMOTO Hiro-o Okayama University Medical School, Lecturer, 医学部・附属病院, 講師 (80304343)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | rheumatoid arthritis / CD4+T cells / Th1 cells / intracellular cytokine staining / interferon-γ / interleukin-4 / interleukin-15 / interleukin-18 / Th・1細胞 / インターフェロン-γ / インターロイキン-18 / インターロイキン-12 / インターロイキン-7 / T細胞増殖因子 / インターフェロン・ガンマ / インターロイキン-10 / RT-PCR法 |
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| Research Abstract |
The inflamed synovium of rheumatoid arthritis (RA) is characterized by massive infiltration of CD4+ T cells. It has recently been indicated that the IFN-γ-dominant Th1-type immune response is involved in the disease process of RA. The cytokine profile of CD4+ T cells infiltrates was compared with that of peripheral blood CD4+ CD45+ T cells in patients with RA by intracellular cytokine staining and flow cytometric analysis. We found that synovial tissue CD4+ T cells contained more Th1-type (IFN-γ) and Th0 type (IFN-γ+IL-4) cells, and that there were unique CD4+ T cells such as those producing both IFN-γ and IL-10/IL-13.
We also found that fibroblast cell lines from RA synovial tissues spontaneously produced the IL-2-like cytokines Il7 and IL-15, which was augmented by stimulation with IL-1 and TNF-α. IL-15 was able to stimulate the proliferation of synovial tissue T cells more potently than IL-2.
Furthermore, the IFN-γ-inducing factor, IL-18, was strongly expressed in the inflammatory joint of RA. Although IL-18 had only minute effect, the level of IFN-γ produced by RA synovial tissues with IL-12 was significantly increased by IL-18, but over 50% reduced by the presence of anti-IL-18.
Taken together, our data support that the immune inflammatory response in RA is mediated predominantly by Th1 cells. Il-15, produced by macrophages and synovial fibroblasts, appears to be the important stimulating factor for T cells. Local IFN-γ production may be regulated primarily by IL-12 and readily augmented by the abundance of IL-18 in RA joints.
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