| Project/Area Number |
14360070
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
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)
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| Co-Investigator(Kenkyū-buntansha) |
KAMINOGAWA Shuichi NIHON UNIVERSITY, COLLEGE OF BIORESOURCE SCIENCES, PROFESSOR, 生物資源科学部, 教授 (50011945)
ISE Wataru THE UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF AGRICULTURAL AND LIFE SCIENCES, ASSISTANT PROFESSOR, 大学院・農学生命科学研究科, 助手 (70323483)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2004: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2002: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | oral tolerance / T cell / intestinal immune system / signal transduction / regulatory T cell / functional food / アポトーシス / IgE / 樹状細胞 / 抗原提示 / 腸内細菌 |
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| Research Abstract |
1.The characteristics of orally tolerized T cells and the molecular mechanisms of their hyporesponsiveness was investigated. We elucidated the following characteristics of orally tolerant T cells. As a consequence of caspase activation, orally tolerant T cells could not form normal TCR signaling complexes associated with GADS-SLP-76. Orally-tolerized T cells showed defects in the translocation of TCR, PKC-θ, and lipid rafts into the interface between T cells and APCs, as well as impairment in vav activation. Thus orally-tolerized T cells were defective in immunological synapse formation. Furthermore, the expression of the protein phosphatase SHP-1 was upregulated in orally tolerized T cells. These observations may account for the hyporesponsive state of orally-tolerized T cells. We also found that T cells from orally tolerant mice could be divided into two populations based on the expression of CD44/CD62L, CD62L^<high>CD44^<low> cells and CD62L^<low>CD44^<high> cells. These cell populations were both hyporesponsive and possessed immunoregulatory functions. Nevertheless, they differed in cytokine secreting capacity and mode of suppression. The results suggested that oral administration of antigen induced two distinct types of hyporesponsive T cells with immunoregulatory function, that could be distinguished by expression of these cell surface molecules.
2.Mice were orally administered with biotinylated antigen and antigen presentation was detected by fluorescence-labeled avidin. The results suggested that B220^+ Peyer's patch dendritic cells presented oral antigen.
3.Germ-free T cell receptor transgenic mice were established and analyzed. It was shown that commensal bacteria affected the T cell cytokine response in the intestinal immune system.
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