2023 Fiscal Year Final Research Report
Identification of Indirect Alloreactive T-Cells and Application to Monitoring of anti-Donor Antibody Sensing
| Project/Area Number |
21K09385
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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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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | Aichi Medical University |
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Principal Investigator |
IWASAKI KENTA 愛知医科大学, 医学部, 准教授 (10508881)
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| Co-Investigator(Kenkyū-buntansha) |
石山 宏平 愛知医科大学, 医学部, 准教授 (50437589)
小林 孝彰 愛知医科大学, 医学部, 教授 (70314010)
三輪 祐子 愛知医科大学, 医学部, 助教 (90572941)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 移植免疫 / ヒト免疫 / エピトープ / 樹状細胞 |
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| Outline of Final Research Achievements |
Generation of donor-specific human leukocyte antigen antibody (DSA) via indirect allorecognition is detrimental to long-term survival of transplant organs. The detection of such immune responses would make it possible to define patients with high risk of sensitization. In this study, we established a novel method for evaluating indirect allorecognition to assess sensitization in kidney transplant recipients. CD4 + T cell proliferation was strongly observed in following coculture with allogeneic antigen-pulsed DC leading to interferon-γ and IL-21 production. In de novo DSA-positive patients, IL-21-produced CD45RA - CD4 + T cells were significantly increased after transplantation compared with before transplantation (9.23 ± 9.08 versus 43.9 ± 29.1, P < 0.001). Assessment of indirect pathway CD4 + T cell response could provide new insights into the underlying mechanism of de novo DSA production, leading to the development of effective strategies against antibody-mediated rejection.
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| Free Research Field |
移植免疫
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| Academic Significance and Societal Importance of the Research Achievements |
臓器移植患者では術後にB細胞を活性化する濾胞性T細胞が増加する。T/B細胞は外来抗原ペプチド断片や、その3次元構造を各々の受容体で認識することになり、抗原決定基はエピトープと呼ばれる。その重要性についてはこれまでin silicoで解析したところ、T/Bの推定エピトープ数の多さと抗ドナーHLA抗体産生に相関関係が認められた。また、エピトープレベルで共通推定ペプチドが存在する場合にドナーHLA特異的抗体が生じやすいことを報告した。この仮説立証ため、樹状細胞にドナー抗原を貪食・提示させ、活性化されるT細胞を検出し移植後の感作状態を評価できるin vitro実験系を構築した。
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