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2001 Fiscal Year Final Research Report Summary

ELUCIDATION OF THE MOLECULAR MECHANISMS OF THE INTESTINAL IMMUNE RESPONSE TO FOOD PROTEIN ANTIGENS

Research Project

Project/Area Number 12660110
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 食品科学・栄養科学
Research InstitutionTHE UNIVERSITY OF TOKYO

Principal Investigator

HACHIMURA Satoshi  GRADUATE SCHOOL OF AGRICUlTURAL AND LIFE SCIENCES, THE UNIVERSITY OF TOKYO, ASSOCIATE PROFESSOR, 大学院・農学生命科学研究科, 助教授 (40238019)

Co-Investigator(Kenkyū-buntansha) KAMINOGAWA Shuichi  GRADUATE SCHOOL OF AGRICUlTURAL AND LIFE SCIENCES, THE UNIVERSITY OF TOKYO, PROFESSOR, 大学院・農学生命科学研究科, 教授 (50011945)
Project Period (FY) 2000 – 2001
Keywordsintestinal immune response / Peyer's patch / oral tolerance / T cell / signal transduction / dendritic cell / interleukin 5 / interleukin 6
Research Abstract

1. Interlaken (IL) -5 and IL-6 secretion of Peyer's patch cells. (1) It was demonstrated that PP dendritic cells (DCs), particularly CD11b^+ DCs produced higher levels of IL-6 compared to SP DCs. (2) We found that naive CD4 T cells had a high capacity to secrete IL-6. (3) We found that IL-2R^+ CD3^-B220^- non T, non-B cells isolated from PP cells secreted IL-5 in response to IL-2. These IL-2R^+ cells did not belong to previously known IL-5 producing cells, such as T cells, mast cells, NK cells or eosinophils. Deoletion of IL-2R^+CD3^-B220^- cells from PP cells resulted in reduced IL-5 production.
2. Signal transduction pathways in orally tolerant CD4 T cells induced in ovalbumin-specific T cell receptor (TCR) transgenic mice fed with ovalbumin was examined. In these T cells (1) impaired phosphorylation of TCR-ζ, ZAP-70, LAT (2) impaired calcium responses and decreased NFAT nuclear translocation, (3) normal activation of ERK and SAPK (MAPK pathway), and (4) impaired degradation of p27^<kip1> induced by IL-2 stimulation was demonstrated. Thus, hyporesponsiveness in the orally tolerant CD4 T cell appears to be associated with two defects : impaired TCR-induced activation of the calcium pathway, and impaired p27 ^<kip1> degradation induced by stimulation thorough IL-2R.

  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] K.Shida, et al.: "Serum IgE response to orally ingested antigen : A novel IgE response model using allergen-specific T cell receptor transgenic mice"J. Allergy Clin. Immunol.. 105. 788-795 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Hashiguchi, et al.: "Th2 polarization enhanced by oral administration of higher doses of antigen"Cytotechnology. 33. 237-245 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Nagafuchi, et al.: "Dietary nucleotides can up-regulate antigen-specific Th1 immune responses and suppress antigen-specific IgE responses in mice"Int. Arch. Allergy Immunol.. 122. 33-41 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Nagafuchi, et al.: "Dietary nucleotides increase the proportion of a TCRγδ^+ subset of intraepithelial lymphocytes (IEL) and IL-7 production by intestinal epithelial cells (IEC) : Implications for modification of cellular and molecular cross-talk between IEL and IEC by dietary nucleotides"Biosci. Biotechnol. Biochem.. 64. 1459-1465 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 八村敏志: "Oral Toleranceをめぐる問題 (1)Oral Toleranceとその誘導機序 b. 抗原構造面から"臨床消化器内科. 15. 291-298 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐藤あゆ子: "樹状細胞と粘膜免疫"アレルギー・免疫. 7. 1451-1455 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Ueda, et al.: "Apoptosis of antigen-specific T cell induced by oral administration of antigen : comparison of intestinal and non-intestinal immune organs"Biosci. Biotechnol. Biochem. 65. 1170-1174 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Asai, et al.: "Orally tolerant CD4 T cells respond poorly to antigenic stimulation but strongly to direct stimulation of intracellular signaling pathways"Cytotechnology. 36. 145-153 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Asai, et al.: "Characteristics of orally tolerized CD4 T cells"Animal Cell Technology : Basic & Applied Aspects. 12. 331-335 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Sato, et al.: "The role dendritic cells play in the cytokine response in Peyer's patches"Animal Cell Technology : Basic & Applied Aspects. 12. 213-217 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Hamada, et al.: "Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine"J. Immunol.. 168. 57-64 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] W.Ise, et al.: "Naive CD4+ T cells exhibit distinct expression patterns of cytokines and cell surface molecules on their primary responses to varying doses of antigen"J. Immunol.. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Yoshida, et al.: "Antigen presentation by Peyer's patch cells can induce both Th1-and Th2-type responses depending on antigen dosage, but a different cytokine response pattern from that of spleen cells"Biosci. Biotechnol. Biochem. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 植田祥啓: "経口免疫寛容の成立機序"医学のあゆみ. 199. 79-84 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Sato, et al.: "Murine Peyer's patch dendritic cells prime naive T cells to produce IFN-γ"Cytotechnology. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Shida, et al: "Serum IgE response to orally ingested antigen : A novel IgE response model using allergen-specific T dell receptor transgenic mice"J. Allergy Clin. Immunol. 105. 788-795 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Hashiguchi, et al: "Th2 polarization ehnanced by oral administration of higher doses of antigen"Cytotechnology. 33. 237-245 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Nagafuchi, et al: "Dietary nucleotides can up-regulate antigen-specific Th1 immune responses and suppress antigen-specific IgE responses in mice"Int. Arch. Allergy Immunol. 122. 33-41 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Nagafuchi, et al: "Dietary nucleotides increase the proportion of a TCRγδ^+ subset of intraepothelial lymphocytes (IEL) and IL-7 production by intestinal epithelial cells (IEC) : Implications for modification of cellular and molecular cross-talk between IEL and IEC by dietary nucleotides"Biosci. Biotechnol. Biochem. 64. 1459-1465 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Ueda, et al: "Apoptosis of antigen-specific T cell induced by administration of antigen : comparison of intestinal and non-intestinal immune organs"Biosci. Biotechnol. Biochem. 65. 1170-1174 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Asai, et al: "Orally toleran CD4 T cells resond poorly to antigenic stimulation but strongly to direct stimulation of intracellular singaling pathways"Cytotechnology. 36. 145-153 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Asai, et al: "Characteristics of orally tolerized CD4 T cells"Animal Cell Technology : Basic & Applied Aspects. 12. 331-335 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Sato, et al: "The role dendritic cells play in the cytokine response in Peyer's patches"Animall Cell Technology : Basic & Applied Aspects. 12. 213-217 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H. Hamada, et al: "Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine"J. Immunol. 168. 57-64 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] W. Ise, et al: "Naive CD4 + T cells exhibit distinct expression patterns of cytokines and cell surface molecules on their primary responses to varying doses of antigen"J. Immunol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Yoshida, et al: "Antigen presentation by Peyer's patch cells can induce both Th1- and Th2-type responses depending on antigen dosage, but a different cytokine response pattern from that of spleen cells"Biosci. Biotechnol. Biochem. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Sato, et al: "Murine Peyer's patch dendritic cells prime naive T cells to produce IFN-γ"Cytotechnology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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