1999 Fiscal Year Final Research Report Summary
Expression of T cell cytokines in the inflamed synovium from patients with rheumatoid arthritis
| 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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| Keywords | rheumatoid arthritis / CD4+T cells / Th1 cells / intracellular cytokine staining / interferon-γ / interleukin-4 / interleukin-15 / interleukin-18 |
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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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Research Products
(14 results)
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[Publications] Kawashima, M., Yamamura, M., Morita, Y., Tanimoto, T., Kurimoto, M., and Makino, H.: "Highly elevated levels of serum interleukin-18 in adult onset Still's disease"Arthritis Rheum.. 41(9). S39 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Kawanaka, N., Yamamura, M., Morita, Y., Kawashima, M., Aita, T., Okamoto, A., and Makino, H.: "CD16ィイD1+ィエD1 blood monocytes are increased in active patients with rheumatoid arthritis"Arthritis Rheum.. 41(9). S165 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Morita, Y., Yamamura, M., Kawashima, M., Harada, S., Tsuji, K., Shibuya, K., Maruyama, K., and Makino, H.: "Flow cytometric single-cell analysis of cytokine production by CD4ィイD1+ィエD1 T cells in synovial tissue and peripheral blood from patients with rheumatoid arthritis"Arthritis Rheum.. 41(9). 1669-1676 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Sato, A., Tsuji, K., Yamamura, M., Morita, Y., Kanzaki, H., Tada, J., Makino, H., and Arata, J.: "Increased type 2 cytokine expression of both CD4ィイD1+ィエD1CD45ROィイD1+ィエD1T cells and CD8ィイD1+ィエD1CD45ROィイD1+ィエD1T cells in blood circulation is associated with high serum IgE but not with atopic dermatitis"J. Invest. Dermatol.. 111(6). 1079-1084 (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Harada, S., Yamamura, M., Okamoto, H., Morita, Y., Kawashima, M., Aita, T., and Makino, H.: "Production of interleukin-7 and interleukin-15 by fibroblast-like synoviocytes from patients with rheumatoid arthritis"Arthritis Rheum.. 42(7). 1508-1516 (1999)
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「研究成果報告書概要(欧文)」より
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