| Project/Area Number |
10306008
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
食品科学・栄養科学
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| Research Institution | THE UNIVERSITY OF TOKYO |
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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)
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| 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)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥37,100,000 (Direct Cost: ¥37,100,000)
Fiscal Year 2000: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1999: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1998: ¥23,800,000 (Direct Cost: ¥23,800,000)
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| Keywords | food allergy / TCR antagonism / altered peptide ligand / intestinal immune system / cytokine / neural cell / nitric oxide / apoptosis / アナログペプチド / 脳細胞 / T細胞 / 細胞死 / p53 / IgE / 神経幹細胞 |
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| 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.
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