1999 Fiscal Year Final Research Report Summary
Analyses of antigen-specific T cells in systemic types of autoimmune disorders.
| Project/Area Number |
10470123
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | The University of Tokyo |
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Principal Investigator |
YAMAMOTO Kazuhiko University of Tokyo, Faculty of Medicine, Professor, 医学部・附属病院, 教授 (80191394)
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| Co-Investigator(Kenkyū-buntansha) |
SHINOHARA Satoshi University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (90282657)
DOHI Makoto University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (60222155)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Autoimmune diseases / antigen-specific T cells / T cell receptor / T cell clone / rheumatoid arthritis / systemic lupus erythematosus |
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| Research Abstract |
The involvement of antigen-specific T cells in the pathogenesis of systemic types of autoimmune disorders is still controversial. Essentially, activated antigen-specific T cells should form accumulating clones among the lymphocyte population. Therefore, it is crucial to detect such T cells in order to know the contribution of antigen -specific immune responses in the diseases. However, the methods available to analyze T cell clonality are still limited. In this respect, we have established a novel method using a combination of reverse transcriptase-polymerase chain reaction of T cell receptor beta chain transcripts and single strand conformation polymorphism (SSCP). Using this method, the dynamic changes of T cell clonal responses during an antigenic stimulation could be monitored. Analyses of several autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus and their animal models, revealed the involvement of antigen specific T cell immune responses. Furthermore, taking advantage of the reproducible mobility of a band in SSCP gel, we are now able to compare identities of the accumulated T cell clones in different samples Without the need for nucleotide sequencing of each clone. Such information can thus elucidate the occurrence of uniform or stable immunological reactions in the patients and also suggests that these reactions play an important role in the pathogenesis. Developing this system, we are also establishing a new strategy to determine the antigen specificities of these in vivo accumulating T cell clones.
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[Publications] Matsui, T., Kurokawa, M., Kobata, T., Oki, S., Azuma, M., Tohma, S., Inoue, T., Yamamoto, K., Nishioka, K., Kato, T.: "Autoantibodies to Tcell co-stimulatory molecules in systemic autoimmune diseases."J. Immunol.. 162. 4328-4335 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Furukawa, H., Murata, S., Yabe, T., Shimbara, N., Keicho, N., Kashiwase, K., Watanabe, K., Ishikawa, Y., Akaza, T., Tadokoro, A., Tohma, S., Inoue, T., Tokunaga K., Yamamoto, K., Tanaka, K., Juji, T.: "Splice acceptor site mutation of transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome"J. Clin. Invest.. 103. 755-758 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Kawahata, K., Misaki, Y., Komagata, Y., Setoguchi, K., Tsunekawa, S., Yoshikawa, Y., Miyazaki, J., Yamamoto, K.: "Altered expression level of a systemic nuclear autoantigen determines the fate of immune response to self."J. Immunol.. 162. 6482-6491 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Takizawa, H., Ohtoshi, T., Kawasaki, S., Kohyama, T., Desaki, M., Kasama, T., Kobayashi, K., Nakahara, K., Yamamoto, K., Matsushima, K., Kudoh S.: "Diesel exhaust particles induce NF-κ B activation in human bronchial epithelial cells in vitro : Importance in cytokine transcription."J. Immunol.. 162. 4705-4711 (1999)
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[Publications] Miyamasu, M., Yamaguchi, M., Nakajima, T., Misaki, Y., Morita, Y., Matsushima, K., Yamamoto, K., Hirai, K.: "Th1-derived cytokine IFN-γ is a potent inhibitor of eotaxin sythesis in vitro."Int. Immunol.. 11. 1001-1004 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Koshino, T., Takano, S., Kitani, S., Ohshima, N., Sano, Y., Takaishi, T., Hirai, K., Yamamoto, K., Morita, Y.: "Novel polymorphism of the 5-lipoxygenase activating protein (FLAP) promoter gene associated with asthma."Mol. Cell. Bio.. 2. 32-35 (1999)
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「研究成果報告書概要(欧文)」より
