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2000 Fiscal Year Final Research Report Summary

THE MOLECULAR MECHANISMS OF IMMUNE RESPONSE AND INTERACTION OF THE IMMUNE AND NERVOUS SYSTEMS IN FOOD ALLERGY

Research Project

Project/Area Number 10306008
Research Category

Grant-in-Aid for Scientific Research (A).

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

Principal Investigator

KAMINOGAWA Shuichi  THE UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF AGRICULTURAL AND LIFE SCIENCES, PROFESSOR, 大学院・農学生命科学研究科, 教授 (50011945)

Co-Investigator(Kenkyū-buntansha) HACHIMURA Satoshi  THE UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF AGRICULTURAL AND LIFE SCIENCES, ASSOCIATE PROFESSOR, 大学院・農学生命科学研究科, 助教授 (40238019)
HISATSUNE Tatsuhiro  THE UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF FRONTIER SCIENCES, ASSOCIATE PROFESSOR, 大学院・新領域創成科学研究科, 助教授 (10238298)
TOTSUKA Mamoru  THE UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF AGRICULTURAL AND LIFE SCIENCES, ASSOCIATE PROFESSOR, 大学院・農学生命科学研究科, 客員助教授 (70227601)
Project Period (FY) 1998 – 2000
Keywordsfood allergy / TCR antagonism / altered peptide ligand / intestinal immune system / cytokine / neural cell / nitric oxide / apoptosis
Research Abstract

1. The response of T cells from transgenic(Tg)mice expressing T-cell receptor(TCR)specific for residues 323-339 of ovalbumin(OVA323-339)could be classified into at least four types according to the pattern of cytokine secretion and induction of antibody production, when a panel of 40 amino-acid substituted analogs of OVA323-339 was used as stimulations. The similarly classified response could be elicited by changing the dose of OVA323-339 used for stimulants. We also found peptides with ability to inhibit the T-cell response to OVA323-339 among the panel of analog peptides. Intraperitoneal administration of the inhibitory peptide could suppress food-allergic reaction in an animal model. 2. The response of the intestinal immune system to orally administrated allergen was examined using the OVA-specific TCR-Tg mice. Peyer's patch cells from OVA-fed TCR-Tg mice secreted IFN-gamma and IL-5 in response to antigen stimulation, and intraepithelial lymphocytes secreted IFN-gamma. The response of splenic CD4 T cells was diminished, indicative of oral tolerance. Ca_<2+> mobilization after TCR-ligation was impaired in these tolerant T cells. OVA feeding induced apoptosis of thymocytes and CD4 T cells in lymph nodes, and oral tolerance was partly abrogated in p53-deficient mice. In addition, the differences in antigen presentation functions between splenic cells and Peyer's patch cells were clarified. 3. The effect of inflammatory cytokines on neural cell response was estimated by an in vitro culture system using embryonic mouse brain cells. As a result, both IL-6 family cytokines and TGF-beta family cytokines induced glial differentiation of neural progenitor cells. In addition, nitric oxide produced by inflammatory type NOS triggered apoptosis of neural cells in a p53-dependent manner. These findings clearly demonstrate the interaction between inflammatory system and nervous system.

  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] M.Kohyama, et. al.: "Selective induction of CD8^+ T cell functions by single substituted analogs of an antigenic peptide : distinct signals for IL-10 production."FEBS Letters. 423. 138-142 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Nakajima-Adachi, et.al.: "Determinant analysis of IgE and IgG4 antibodies and T cells specific for bovine α_<S1>-casein from the same patients allegic to cows milk : Existence of α_<S1>-casein-specific B cells and T cells charactenstic in cow's milk allergy."J.Allergy Clin.Immunol.. 101. 660-671 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Yoshida, et.al.: "Induction of oral tolerance in splenocyte-reconstituted SCID mice."Clin.Immunol.Immunopathol.. 87. 282-291 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Takahashi, et.al.: "MHC class-II/T-cell receptor interactions potentiate secretion of IgG but not IgM in response to T-dependent antigens."Immunology Letters. 61. 97-101 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Matsumoto, et.al.: "Intranasal administration of denatured type II collagen and its fragments can delay the onset of collagen-induced arthritis."Clin.Immunol.Immunopathol.. 88. 70-79 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Totsuka, et.al.: "Enhancement of antigen-specific IFN-γ production from CD8^+ T cells by single amino acid-substituted peptide derived from bovine αs1-casein."Clin.Immunol.Immunopathol.. 88. 277-286 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Takahashi, et.al.: "Autocrine B-cell stimulation by interleukin-2 during a cognate interaction with T-cells."Immunol.Lett.. 65. 183-188 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [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(和文)」より
  • [Publications] K.Nakashima, et.al.: "Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300."Science. 284. 479-482 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Yamada, et.al.: "NMDA receptor mediated Ca2+ responses in neurons differentiated from p53-/-immortalized murine neural stem cells."Neurosci.Lett.. 264. 165-167 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Nakashima, et.al.: "Developmental requirement of gp130 signaling in neuronal survival and astrocyte differentiation."J.Neurosci.. 19. 5429-5434 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] C-W.Lien, et.al.: "Role of olfaction in food preference as evaluated in an animal model."Biosci.Biotechnol.Biochem.. 63. 1553-1556 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Katakura, et.al.: "Accelerated secretion of mutant β-lactoglobulin in Saccharomyces cerevisiae resulting from a single amino acid substitution."Biochem.Biophys.Acta. 1432. 302-312 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [Publications] M.Toda, et.al.: "Downregulation of antigen-specific antibody production by T-cell receptor antagonist peptides in vivo."Eur.J.Immunol.. 30. 403-414 (2000)

    • 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 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."Cyotechnology. 33. 237-245 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Yanagisawa, et.al.: "Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gp130, and a transcription factor, STAT3."J.Neurochem.. 74. 1498-1504 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Yoshida, et.al.: "Glutamate triggers elevation of intracellular Ca^<2+> concentration in neural precursor cells."Cytotechnology. 33. 157-165 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Kaji, et.al.: "Immortalized hippocampal neural precursor cell lines."Cytotechnology. 33. 53-61 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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] 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).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 戸塚護、上野川修一: "アレルギー反応抑制の細胞工学的基盤"日本農芸化学会誌. 74. 1008-1011 (2000)

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

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

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [Publications] M.Kohyama, et.al.: "Selective induction of CD8^+ T cell functions by single substituted analogs of an antigenic peptide : distinct signals for IL-10 production."FEBS Letters. 423. 138-142 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Nakajima-Adachi, et.al.: "Determinant analysis of IgE and IgG4 antibodies and T cells specific for bovine αs1-casein from the same patients allergic to cow's milk : Existence of αs1-casein-specific B cells and T cells characteristic in cow's milk allergy."J.Allergy Clin.Immunol.. 101. 660-671 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Yoshida, et.al.: "Induction of oral tolerance in splenocyt-reconstituted SCID mice."Clin.Immunol.Immunopathol.. 87. 282-291 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Takahashi, et.al.: "MHC class II/T-cell receptor interactions potentiate secretion of IgG but not IgM in response to T-dependent antigens."Immunology Letters. 61. 97-101 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Matsumoto, et.al.: "Intranasal administration of denatured type II collagen and its fragments can delay the onset of collagen-induced arthritis."Clin.Immunol.Immunopathol.. 88. 70-79 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Totsuka, et.al.: "Enhancement of antigen-specific IFN-γ production from CD8^+ T cells by single amino acid-substituted peptide derived from bovine αs1-casein."Clin.Immunol.Immunopathol.. 88. 277-286 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Takahashi, et.al.: "Autocrine B-cell stimulation by interleukin-2 during a cognate interaction with T-cells."Immunol.Lett.. 65. 183-188 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Kohyama, et.al.: "Cytolytic and IFN-γ-producting activities of γ δT 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
  • [Publications] K.Nakashima, et.al.: "Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300."Science. 284. 479-482 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Yamada, et.al.: "NMDA receptor mediated Ca2+ responses in neurons differentiated from p53-1-immortalized murine neural stem cells."Neurosci.Lett.. 264. 165-167 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Nakashima, et.al.: "Developmental requirement of gp130 signaling in neuronal survival and astrocyte differentiation."J.Neurosci.. 19. 5429-5434 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] C-W.Lien, et.al.: "Role of olfaction in food preference as evaluated in an animal model."Biosci.Biotechnol.Biochem.. 63. 1553-1556 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Katakura, et.al.: "Accelerated secretion of mutant β-lactoglobulin in Saccharomyces cerevisiae resulting from a single amino acid substitution."Biochim.Biophys.Acta.. 1432. 302-312 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] W.Ise, et.al.: "Primary response of naive CD4^+ 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
  • [Publications] M.Toda, et.al.: "Downregulation of antigen-specific antibody production by T-cell receptor antagonist peptides in vivo."Eur.J.Immunol.. 30. 403-414 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [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(欧文)」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(欧文)」より
  • [Publications] M.Yanagisawa, et.al.: "Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gp130, and a transcription factor, STAT3"J.Neurochem.. 74. 1498-1504 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Yoshida, et.al.: "Glutamate triggers elevation of intracellular Ca^<2+> concentration in neural precursor cells."Cytotechnology. 33. 157-165 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kaji, et.al.: "Immortalized hippocampal neural precursor cell lines."Cytotechnology. 33. 53-61 (2000)

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

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

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Published: 2002-03-26  

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