| Project/Area Number |
18K16268
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | St. Marianna University School of Medicine (2021)
Toho University (2018-2020) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 制御性T細胞 / 臓器移植 / 免疫寛容 / 混合キメラ / Foxp3 / Treg / ジフテリアトキシン / 混合キメリズム / 末梢性免疫寛容 / 臓器特異的抗原 |
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| Outline of Final Research Achievements |
We created mixed chimeras between C57BL/6-Foxp3-DTR recipients and F1 donors (C57BL/6-FoxpeDTR x 61620; DBA/2). Both recipient and donor-derived lymphocytes coexisted and chimeras had donor-specific tolerance against transplanted organs (skin or heart). Organ transplant tolerance was broken if regulatory T cells were depleted. We also created C57BL/6-Rag1 KO recipients, lacking both T and B cells, that received both skin and heart from DBA/2 donors, and adoptively transferred splenocytes from mixed chimeras that rejected skin or heart of DBA/2. In Rag1 KO recipients, the organs (skin or heart) that were rejected in mixed chimeras were rejected again after adoptive transfer of splenocytes, although allograft tolerance against the other organ (skin or heart) that were not rejected by mixed chimeras persisted after adoptive transfer. These results suggested that organ allograft tolerance in mixed chimeras was established against organ specific antigens regulated by regulatory T cells.
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| Academic Significance and Societal Importance of the Research Achievements |
混合キメラにおけるドナー特異的免疫寛容は、末梢における制御性T細胞を消去すると破綻することがわかったが、そのメカニズムとして制御性T細胞が臓器特異的抗原を対象として免疫寛容を成立させていることが示唆された。
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