Molecular biology of oligoclonal ββィイD1+ィエD1 T cells in murine inflammatory bowel disease
| Project/Area Number |
10670302
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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 |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
TAKAHASHI Ichiro Res. Inst. microbial Dis., Osaka University Associate Professor, 微生物病研究所, 講師 (20206791)
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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 |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | ββ T cells / Th2 cytokine / IBD / mucosal T cells / clonality / gut-flora / PCR-SSCP / TCR beta / beta / クロナリティ- / 腸内細菌 |
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| Research Abstract |
A population of CD4ィイD1+ィエD1 T cells with TCR β-chain without TCR α-chain (CD4ィイD1+ィエD1,ββィイD1+ィエD1 T cells) producing Th2-type cytokines increased in the mucosal and peripheral tissues of TCR α-chain deficient mice with inflammatory bowel disease (IBD). Analysis of TCR-β immunoprecipitates by two-dimensional electrophoresis and RT-PCR revealed TCR of the CD4ィイD1+ィエD1 T cells was a homodimer of TCR β-chains. PCR-SSCP analyses of TCR νβ-chain transcripts of the ββィイD1+ィエD1 T cells revealed monoclonal to oligoclonal accumulation of the cells in the colon, suggestingclonal expansion of the mucosal ββィイD1+ィエD1 T cells upon the stimulation with gut-derived antigens. The homodimer of TCR β-chains on the ββィイD1+ィエD1 T cells was a biologically functional receptor which transducedactivation signals provided by MHC-class ll-associated peptidic antigens and superantigens. The importance of the Th2-biased ββィイD1+ィエD1 T cells was also supported by the finding that treatments of the mutant mice with mAb against TCR βor lL-4 suppressed the onset of IBD. The Th2-biased cytokine production by the ββィイD1+ィエD1 T cells in IBD mice could be attributed to the high incidence of Bacteroides vulgatus. Rectal administration of non-diseased mice with B. vulgatus resulted in the development of Th2-type ββィイD1+ィエD1 T cell-induced colitis. These findings suggest that the generation of oligoclonal Th2-type ββィイD1+ィエD1 T cells plays a critical role for the development of IBD.
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Report
(3 results)
Research Products
(18 results)
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[Publications] Takahashi, I., H. Iijima, D. Kishi, S. Hamada, R. Katashima, M. Itakura, and H.Kiyono: "Biochemical characterization of CD4ィイD1+ィエD1, αィイD1-ィエD1βィイD1+ィエD1 T cells in TCR-α mutant mice with inflammatory bowel disease. In : Induction and modulation of gastrointestinal nflammation. M. Zeitz (eds.)"Kluwer academic publishers, Lancaster, UK. 142-146 (1998)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Publications] Boyaka, P. N., M. Marinaro, J. L. VanCott, I. Takahashi, K. Eujihashi, M. Yamamoto, F. Van Ginkel, R. J. Jackson, H. Kiyono, and J. R. McGhee: "Strategies for mucosal vaccine development"Am. J. Tropp. Med. Hyg. 60. 35-45 (1999)
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Publications] Takahashi,T.,Iijima,H.,et al.: "Induction and modulationm of gastrointestinal inflammation" Stallmach,A.,Zeitz,M.,Strober,W.,MacDonald,TT.,and Lochs,H., 142-146 (1999)
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