| Project/Area Number |
17K18137
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Urology
General surgery
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
ISHII Rumi 東京女子医科大学, 医学部, 助教 (40751178)
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| Research Collaborator |
ISHII Yasuyuki
FUKUDA Emi
ABE Ryo
OKUMI Masayoshi
TANABE Kazunari
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 免疫寛容 / 移植片対宿主病 / ナチュラルキラーT細胞 / 制御性T細胞 / T細胞 / 抗CD40リガンド抗体 / 臓器移植 / 移植医療 / 再生医療 / α-galactosylceramide / MEK/ERK signaling / NKT 細胞 / GVHD / NKT細胞 / 移植・再生医療 / 免疫学 |
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| Outline of Final Research Achievements |
Transplant tolerance induction makes it possible to preserve functional grafts for a lifetime without immunosuppressants. One powerful method is to generate mixed hematopoietic chimeras in recipients by adoptive transfer of donor-derived bone marrow cells (BMCs). In our murine transplantation model, we established a novel method for mixed chimera generation using sublethal irradiation, CD40-CD40L blockade, and invariant natural killer T-cell activation. However, numerous BMCs that are required to achieve stable chimerism makes it difficult to apply this model for human transplantation. Here, we show that donor-derived splenic T cells could contribute to not only the reduction of BMC usage but also the establishment of complete chimerism in model mice. By cotransfer of T cells together even with one-fourth of the BMCs used in our original method, the recipient mice yielded complete chimerism and could acquire donor-specific skin-allograft tolerance.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で確立した移植免疫寛容誘導法は少ない骨髄細胞数で完全キメラを誘導できることから、移植免疫寛容の臨床応用により近づいたと考える。さらに、本研究成果の対象は臓器移植や血液がんのみならず、低侵襲な骨髄移植法の確立による自己免疫疾患患者の骨髄置換による治療や近年進歩の著しい再生医療分野における免疫寛容誘導に展開する可能性もある。本研究の成果は、新しい免疫治療分野を生み出す発展性があると期待できる。
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