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Molecular biology of extrathymic T cells for the development of mucosal inflammation

Research Project

Project/Area Number 12670303
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionOSAKA UNIVERSITY

Principal Investigator

TAKAHASHI Ichiro  RESEARCH INSTITUTE FOR MICROBIAL DISEASES, OSAKA UNIVERSITY, ASSISTANT PROFESSOR, 微生物病研究所, 講師 (20206791)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsMUCOSAL IMMUNOLOGY / EXTRATHYMIC T CELLS / INFLAMMATION / CROHN'S DISEASE / PUBLIC CDR3 MOTIF / T細胞 / 炎症性腸疾患
Research Abstract

IL-10 is an important regulatory cytokine in the mucosal immune system, as supported by the fact that mice deficient in IL-10 spontaneously develop Crohn's disease-like colitis. An aberrant, Th1-driven CD4^+ T-cell response to enteric bacteria seems to be important in the pathogenesis of this murine colitis. However, no specific bacteria or bacterial products have been identified, whether the colitis is mediated by the activation of CD4^+ T cells that recognize specific peptide-MHC complexes is controversial. In this study, we analyzed the TCRβ chain CDR3 length spectratype of colonic CD4^+ T cells isolated from diseased IL-10-deficient mice by using the Immunoscope technique. Screening of the diseased interleukin-10 deficient mice resulted in a restricted clonotype in TCR Vβ 13 and 14 subfamilies of colonic CD4^+ T cells. In contrast, a Gaussian distribution of clonotype of individual TCR Vβ subsets was observed in CD4^+ T cells from the peripheral lymphoid tissues. Although individua … More l variability in the disease-related response was also noted in other IL-10-deficient mice maintained in La Jolla and Osaka, perhaps because of different stages of the disease, genetic background, or the housing environment, colitis-related public clones seemed to be shared in all the tested diseased mice. To address whether public clones were involved, we determined DNA sequence of the clones. Public motifs were shared in colonic CD4^+ T cells from different background interleukin-10 deficient mice with colitis. The frequently found motifs were SXDWG and SATGNYAEQ. These motifs were not seen in the peripheral lymphoid tissues of diseased mice as well as the colon of nondiseased mice. Thus, the common motif may be related to a public gut-derived antigen, which could be important for the development of pathogenic CD4^+ T cells in this IBD model. The selection of Vβ-Jβ usage is perhaps stochastic in individual mice ; however, the epigenetic generation of SXDWG motif by the recombination machinery and selection for this motif in the gut environment could be : important for triggering IBD. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Takahashi, I., Matsuda, J., et al.: "Colitis-related public T cells are selected in the colonic lamina propria of IL-10 deficient mice"Clinical Immunology. (印刷中). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kweon, M., Takahashi, I., et al.: "Development of antigen-induced enterocolitis in SCID mice reconstituted with spleen-derived memory type CD4CD45RB T cells"Gut. 50巻. 299-306 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kim, J., Takahashi, I., et al.: "Influence of enterotoxin on the mucosal intranet : selective inhibition of extrathymic T cell development in the intestinal IELs by oral exposure to heat-labile toxin"Eur. J. Immunol.. 31巻. 2960-2969 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kunisawa, J., Takahashi, I., et al.: "Sendai virus fusion proten mediates simultaneous induction of MHC class I/II dependent mucosal and systemic immune responses via NALT system"J. Immunol.. 167巻. 1406-1412 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yura, M., Takahashi, I., et al.: "Role of MOG-specific Th1 type GFP+ CD4+ T cells for the development of experimental autoimmune encephalomyelitis"J. Autoimmunity. 17巻. 17-25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 高橋 一郎: "粘膜免疫:消化管の意外な働きと経口ワクチン"清野宏, 石川博通, 名倉宏 編, 中山書店, 東京. 310(224-239) (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kweon M., M. Yamamoto, M. Kajiki, I. Takahashi, and H. Kiyono: "Spleen derived large intestinal CD4+ αβ T cells play a central role for the development of STAT-6-mediated allergic diarrhea"J. Clin. Invest.. 106. 199-206 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kishi, D., I. Takahashi, Y. Kai, H. Tamagawa, H. Iijima, T. Ito, S. Obunai, R. Nezu, H. Matsuda, H. Kiyono: "Alteration of Vβ usage and cytokine production of CD4+ββ T cells by elimination of Bacteroides vulgatus prevents colitis in TCR alpha-chain deficient mice"J. Immunol.. 165. 5891-5899 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto, M., H. Kiyono, M. Kweon, S. Yamamoto, H. Kurazono, K. Imaoka, H. Bluethmann, I. Takahashi, Y. Takeda, M. Azuma, and J. R. McGhee: "Enterotoxin adjuvants induce distinct effects on APCs and T cells and results in either IL-4-dependent or -independent mucocal immune responses"J. Infect. Dis.. 182. 180-190 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kunisawa, J., A. Okudaira, Y. Tsutsumi, I. Takahashi, T. Nakanishi, H. Kiyono, and T. Mayumi: "Characterization of mucoadhesive microspheres for the induction of mucosal and systemic immune responses"Vaccine. 19. 589-594 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yura, M., I. Takahashi, M. Serada, T. Koshio, K. Nakagami, Y. Yuki, and H. Kiyono: "Role of MOG-stimulated Th1 type "light-up" (GFP+) CD4+ T cells for the development of experimental autoimmune encephalomyelitis (EAE)"J. Autoimmunity. 17. 17-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurisawa, J., T. Nakanishi, I. Takahashi, A. Okudaira, Y. Tsutsumi, K. Katayama, S. Nakagawa, H. Kiyono, and T. Malumi: "Sendai virus fusion protein-mediates simultaneous induction of MHC class I/II-dependent mucosal and systemic immune responses via the nasopharyngeal-associated lymphoreticular tissue i immune system"J. Immunol.. 167. 1406-1412 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kim, J., I. Takahashi, Y. Kai, and H. Kiyono: "Influence of enterotoxin on the mucosal intranet : selective inhibition of extrathymic T cell development in the intestinal intraepithelial lymphocytes by oral exposure to heat-labile toxin"Eur. J. Immunol.. 31. 2960-2969 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kweon, M., I. Takahashi, M. Yamamoto, M. Jang, N. Suenobu, and H. Kiyono: "Development of antigen-induced enterocolitis in SCID mice reconstituted with spleen-derived memory type CD4+ CD45RB+ T cells"Gut. 50. 299-306 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahashi, I., J. Matsuda, L. Gapin, H. De Winter, Y. Kai, H. Tamagawa, M. Kronenberg, and H. Kiyono: "Colitis-related public T cells are selected in the colonic lamina propria of IL-10-deficient mice"Clinical Immunology. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] De Winter, H., D. Elewaut, O. Turovskaya, M. Huflejt, C. Shimeld, A. Hagenbaugh, S. Binder, I. Takahashi, M. Kronenberg, and H. Cheroutre: "Modulation of mucosal immune responses through IL-10 produced by intestinal epithelial cells in IL-10 transgenic mice"Gastroenterology. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahashi, I., Matsuda, J., et al.: "Colitis-related public T cells are selected in the colonic lamina propria of IL-10 deficient mice"Clinical Immunology. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kweon, M., Takahashi, I., et al.: "Development of antigen-induced enterocolitis in SCID mice reconstituted with spleen-derived memory type CD4CD45RB T cells"Gut. 50巻. 299-306 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kim, J., Takahash, I., et al.: "Influence of enterotoxin on the mucosal intranet : selective inhibition of extrathymic T cell development in the intestinal IELs by oral exposure to heat-labile toxin"Eur. J. Immunol.. 31巻. 2960-2969 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kweon,M.: "Spleen derived large,intestinal CD4^+αβ T cells play a central role for the development of Stat-b-mediated allergic diarrhea"Journal of Clinical Investigation. 106巻. 199-206 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kishi,D.: "Alteration of Vβ usage and cytokine production of CD4^+ ββ T cells by elimination of B.vulgatus prevents colitis in TCR α^<-1-> mice"Journal of Immunology. 165巻. 5891-5899 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高橋一郎: "炎症性腸疾患:IBDのマウス病態モデルから何を学ぶのか?"感染・炎症・免疫. 30巻. 94-103 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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