| Project/Area Number |
17590620
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KAKIMI Kazuhiro The University of Tokyo, Faculty of Medicine, Assistant Professor, 医学部附属病院, 客員助教授 (80273358)
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| Co-Investigator(Kenkyū-buntansha) |
KURACHI Makoto The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (00396722)
MATSUSHIMA Kouji The University of Tokyo, Faculty of Medicine, Professor, 大学院医学系研究科, 教授 (50222427)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | HBV / CTL / memory T cell / vaccine / regulatory T cell / 抑制性T細胞 / DNAワクチン |
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| Research Abstract |
In this study, we demonstrated the new concept for the maintenance of memory T cell response. Memory T cells can persist for a long period of time by rejuvenation of T cell memory. Memory CD8+T cells generated during an immune response are long-lived and self-renewing, offering enhanced host protection against re-infection. However, how an antigen- specific population of memory T cells is maintained throughout repetitive infections over potentially a lifetime is not known. Here we investigated the generation and maintenance of antigen- specific CD8+T cells and revealed the new concept that showing dynamic turnover of an antigen-specific memory T cell population during repeated antigen challenge in vivo. We demonstrated that a primary response potentially occurs upon every recall response and find that the skewed T-cell receptor(TCR) repertoire of pre-existing memory T cells is partly corrected by diversity in a newly formed(primary) population. Importantly, memory T cells generated in a more recent antigen encounter expand more vigorously in a subsequent recall response. A primary response during re-challenge therefore restores both the TCR diversity and proliferative potential of the memory T cell population. These findings indicate that memory T cell populations evolve over multiple challenges, favoring memory T cells generated in more recent encounters, and suggest that these primary populations have essential roles in the perpetuation of antigen-specific T cell populations.
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