| Project/Area Number |
16K11071
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
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| Research Collaborator |
IKEMIYAGI masako
ISHII yasuyuki
ISHII rumi
OKUMI masayoshi
OMOTO kazuya
KATSUMATA Haruki
KAWAGUCHI emi
KANZAWA taichi
SAIGA kan
HASEGAWA junpei
HIRAI toshihito
FUKUDA hironori
MIYAIRI satoshi
YAMAKAWA takafumi
YOKOO takashi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 同種異系キメラ誘導 / 移植 / 免疫寛容 / タクロリムス / エベロリムス / 制御性T細胞 / 心臓移植 / 免疫誘導 / Tacrolimus / Everolimus / 臓器移植 / 調節性T細胞 / 免疫抑制剤 |
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| Outline of Final Research Achievements |
We previously reported a mixed hematopoietic chimerism induction regimen that promotes regulatory T cell (Treg) proliferation by stimulating invariant natural killer T cells under CD40 blockade. Here we evaluated the impact of tacrolimus (TAC) or everolimus (EVL) on this regimen. In the immunosuppressive drug-dosing phase, peripheral blood chimerism was comparably maintained by both TAC and EVL. After dosing was discontinued, TAC-treated mice showed gradual graft rejection, whereas EVL-treated mice sustained long-term robust chimerism. Treg from TAC-treated mice showed lower expression of both Ki67 and cytotoxic T lymphocyte antigen-4, and lower suppressive activity in vitro than those from EVL-treated mice, indicating that TAC negatively impacted the regimen by interfering with Treg proliferation and activation. Our results suggest that the usage of calcineurin inhibitors should be avoided if utilizing the regimen to induce Treg for the establishment of mixed hematopoietic chimerism.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫寛容の確立は臓器移植患者における免疫抑制剤の永続的内服を不要とするだけでなく、自己免疫性疾患の根治治療にも応用可能である。しかし、臨床応用を考慮すると、移植後初期の拒絶反応を抑制するため従来の免疫抑制剤の一時的な併用は必須と考えられる。本研究では我々の報告した免疫寛容誘導モデルを用いて、免疫抑制剤が及ぼす影響を明らかとし、免疫寛容誘導における免疫抑制剤使用の在り方について意義深い提案ができたと考えられる。
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