| Project/Area Number |
17390142
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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 |
Immunology
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| Research Institution | Nagoya University |
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Principal Investigator |
SUZUKI Haruhiko Nagoya University, Graduate School of Medicine, Associate Professor (90283431)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Kozue Chubu University, Life Health Sciences, Associate Professor (80345884)
NAKASHIMA Izumi Chubu University, Life Health Sciences, Professor (40022826)
HAYAKAWA Akemi Tokyo University of Science Yamaguchi, Industrial Science and Technology, Associate Professor (70412377)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2006: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2005: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Immune regulation / Regulatory T cells / CD8^+ T cells / EAE / CD122 / CXCR3 / CD8 |
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| Research Abstract |
1. Mechanism of the effect of CD8^+CD122^+ regulatory T cells
We investigated how murine CD8^+CD122^+ regulatory T cells suppress their target cells by using in vitro culture systems. As a result, we found that these regulatory T cells directly recognized activated T cells without intervention of antigen-presenting cells and regulated them. The interactions between MHC class I and T cell receptor and between CD28 and CD80/CD86 were important in the process of regulation. The regulatory T cells that had recognized their target cells became active regulatory cells and regulated them by producing IL-10.
2. Effect of CD8^+CD122^+ regulatory T cells on autoimmune diseases
We investigated on the effect of CD8^+CD122^+ regulatory T cells using murine model of EAE (Experimental Autoimmune Encephalomyelitis). In mice that had been treated with anti-CD122 antibody that depleted CD8^+CD122^+ regulatory T cells, symptoms of EAE continued for more than6 weeks without improvement. On the other hand, tr
… More
ansfer of CD8^+CD122^+ regulatory T cells into those mice that had been treated with anti-CD122 antibody and continued the EAE symptoms at the
peak level dramatically caused the quick reduction of EAE symptoms. Thus, it was clearly proved that CD8^+CD122^+ regulatory T cells play an important role in the recovery from the disease that based on the anomaly of immune system.
3. Search for human regulatory T cells
Because there are no CD8^+CD122^+ cells in human, we needed to search human CD8^+ regulatory T cells using other markers than CD122. We performed DNA micro-array analysis to compare the gene expression profile between CD8^+CD122^+ cells and CD8^+CD122^- cells. We found CXCR3 as a candidate gene, and actually the expression of CD122and that of CXCR3was well correlated in mouse CD8^+cells. There are also human CD8^+ cells that express CXCR3and such CD8^+CXCR3^+ cells showed immune regulating activity such as suppressing the production of IFN_γ from the CD8^+CXCR3 cells. Thus, CD8^+CXCR3^+ cells work as regulatory T cells that correspond to murine CD8^+CD122^+ cells. Less
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