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ESTABLISHMENT OF NOVEL EXPERIMENTAL SYSTEM(S) FOR EVALUATION OF THE IMMUNE FUNCTION OF FOOD COMPONENTS USING CELLS FROM THE INTESTINAL IMMUNE SYSTEM

Research Project

Project/Area Number 11556023
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

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)

Co-Investigator(Kenkyū-buntansha) 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)
HISATSUNE Tatsuhiro  GRADUATE SCHOOL OF FRONTIER SCIENCES, THE UNIVERSITY OF TOKYO, ASSOCIATE PROFESSOR, 大学院・新領域創成科学研究科, 助教授 (10238298)
TOTSUKA Mamoru  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, 客員助教授 (70227601)
WATANABE Hiroko  KANAGAWA PREFECTURAL PUBLIC HEALTH LABORATORY, RESEARCHER, 研究員
NAGAFUCHI Shinya  MEIJI MILK PRODUCTS CO., NUTRITION SCIENCE INSTITUTE, RESEARCHER, 栄養科学研究所, 研究員
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥7,700,000 (Direct Cost: ¥7,700,000)
Keywordsfood / immune function / nucleotide / interleukin 7 / intestional epithelial cell / ATBC / IgA / allergy / 腸管免疫系 / 化学物質 / 経口免疫寛容 / 小腸上皮 / T細胞 / 腸管 / サイトカイン
Research Abstract

1. Analysis of intestinal immune system. (1) Feeding OVA diet to OVA-specific T cell receptor transgenic (TCR-Tg) mice enhanced interleukin (IL)-5 and IL-6 secretion of lamina propria lymphocytes. Feeding of OVA diet to these TCR tg mice also resulted in allergic reactions in the small intestine, suggesting its usefulness as an animal model for gastrointestinal food allergy^* We found that when Peyer's patch dendritic cells were added to cultures containing OVA, TCR-TG T cells and B cells, the secretion of IgA was induced.
2. Examination of the immune function of food components using cells from the intestinal immune system, (1) ,Effect of dietary nucleotides on the response of gut-associated lymphoid tissue was investigated. The proportion of T-cell receptor (TCR) γ0 intraepithelial lymphocytes (IEL) in BALB/c mice fed a diet supplemented with nucleotides (NT(+) diet) was significantly higher than that in mice fed the nucleotide-free control diet. Intestinal epithelial cells (IEC) from NT(+) diet-fed mice produced higher levels of interlocking (IL-) 7 and TGF-β, which are important in the development of TORγδo^+ IEL and in IgA responses, respectively, than those from control diet-fed mice. When nucleotides were added to a primary culture of mouse IEC, secretion of EL-7, but not that of TGF-β, was increased. These results demonstrate that nucleotides can modify directly the secretion of IL-7 from IEC, and; suggest that the mechanisms underlying the increased secretion of IL-7 from IEC in mice fed the NT(+) diet were different from those for the increased secretion of TGF-β. (2) Oral administration of acetyl tributyl citrate (ATBC), which is a plasticizer used in food containers, affected the histamine content of the intestine of OVA-fed TCR-Tg mice, suggesting that ATBC modified allegic reactions in the intestine.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (58 results)

All Other

All Publications (58 results)

  • [Publications] M.Kohyama, et al.: "Cytolytic and IFN-y-producing activities of γδ T cells in the mouse intestinal epithelium are T cell receptor-β-chain dependent"Proc. Natl. Acad. Aci. USA. 96. 7451-7455 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] W.Ise, et al.: "Primary response of naive CD4+ T cells to amino-acid-substituted analogs of an antigenic peptide can show distinct activation patterns in terms of cytokine secretion and helper activity for antibody production"FEBS letters. 465. 28-33 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Oida, et al.: "Role of gut cryptopatches in early extrathymic maturation of intestinal intraepithelial T cells"J. Immunol. 164. 3616-3626 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Suzuki. et al.: "Gut Cryptopatches : direct evidence of extrathymic anatomical sites for intestinal T lymphopoiesis"Immunity. 13. 691-702 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 足立はるよ, 上野川修一: "食物アレルゲンと腸管免疫システム"アレルギー科. 9. 89-6 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 上野川修一: "食品の機能性1-免疫系に対する作用を中心として-"遣伝. 54. 22-26 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 八村敏志, 上野川修一: "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
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 上野川修一: "食品アレルギーの誘導・抑制に関与する腸管免疫の特性に関する研究"日本農芸化学会誌. 75. 1-20 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Kohyama, et al: "Cytolytic and IFN-γ-producting activities of γδT cells in the mouse intestinal epithelium are T cell receptor-γ-chain dependent"Proc. Natl. Acad. Aci. USA. 96. 7451-7455 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] W. Ise, et al: "Primary response of native CD4^+ T cells to amino-acid-substituted analogs of an antigenic peptide can show distinct activation patterns in terms of cytokine secretion and helper activity for antibody production"FEBS letters. 465. 28-33 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Shida, et al: "Serum IgE response to orally ingestd antigen : A novel IgE response model using allergen-specific T cell erceptor transgenic mice"J. Allergy Chin. Immunol.. 105. 788-795 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T. Oida, et al: "Role of gut cyptopatches in early extrathymic maturation of intestinal intraepithelial T cells"J. Immunol.. 164. 3616-3626 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Nagafuchi, et al: "ietary 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
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S. Nagafuchi, et al: "Dietary nucleotides increase the proportion of a TCR_<γδ>^+ 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(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K. Suzuki, et al: "Gut Cryptopatches : direct evidence of extathymic anatomical sites for intestinal T lymphopoiesis"Immunity. 13. 691-702 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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. iotechnol. Biochem. 65. 1170-1174 (2001)

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

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

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [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 doese of antigen"J. Immunol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A. Sato, et al: "Murine Peyer's patch dendritic cells prime native T cells to produce IFN-γ"Cytotechnology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2001 Annual Research Report
  • [Publications] A.Sato, et al.: "Murine Peyer's patch dendritic cells prime naive T cells to produce IFN-γ"Cytotechnology. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [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)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Hashiguchi, et.al.: "Th2 polarization enhanced by oral administration of higher doses of antigen."Cytotechnology. 33. 237-245 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Oida, et.al.: "Role of gut cryptopatches in early extrathymic maturation of intestinal intrapithelial T cells."J.Immunol. 164. 3616-3626 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] K.Suzuki, et.al.: "Gut Cryptopatches : direct evidence of Extrathymic anatomical sites for intestinal T lymphopoiesis."Immunity. 13. 691-702 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Nagafuchi, et.al.: "Dietary nucleotides can up-regulate antigen-specfic Th1 immune responses and suppress antigen-specific IgE responses in mice."Int.Arch.Allergy Immunol.. 122. 33-41 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Nagafuchi, et.al.: "Dietary nucleotides increase the proportion of a TCRγδ^+ subset of intraepithelial lymphocytes (IEL) and IL-7 prodution 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)

    • Related Report
      2000 Annual Research Report
  • [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. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] 足立はるよ,上野川修一: "食物アレルゲンと腸管免疫システム"アレルギー科. 9. 89-96 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 上野川修一: "食品の機能性I-免疫系に対する作用を中心として-"遺伝. 54. 22-26 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 八村敏志,上野川修一: "Oral Toleranceをめぐる問題(1)Oral Tolernace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)

    • Related Report
      2000 Annual Research Report
  • [Publications] 上野川修一: "食品アレルギーの誘導・抑制に関する腸管免疫の特性に関する研究"日本農芸化学会誌. 75. 1-20 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kohyama,M. ら: "Cytolytic and IFN-γ-Producting activeties of γδT cells in the mouse intestinal epithelium are T cell receptor β chain dependennt"Proc.Natl.Acad.Aci.USA. 96. 7451-7455 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ise,W. ら: "Primary response of naive CD4+T cells to amino-acid-substituted analogs of an antigenic peptide can show destinct activation patterns in terms of cytokine secretion and helper activity for antibody production"FEBS letters. 465. 28-33 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Oida,T. ら: "Role of gut cryptopatches in early extrathymic maturation of intestinal intrapithelial T cells"J.Immunol. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Shida,K. ら: "Serum IgE resuponse to orally ingested antigen : a novel IgE response model using allergen-specific T cell receptor transgenic mice"J.Allergy Clin.Immunol.. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagafuchi,S. ら: "Dietary nucleotides up-regulate antigen-specific Th1 immune responses and suppress antigen-specific IgE responses in mice"Int.Arch.Allergy Immunol.. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Hashiguchi,M ら: "Th2 polarization enhanced by oral administration of higher doses of antigen"Cytotechnology. (印刷中).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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