| Project/Area Number |
17K11209
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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 | 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) |
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) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 免疫順応 / 免疫寛容 / アロ応答 / PD-1/PD-L1 / CD4 T-cell / 移植免疫 / CD4 T細胞 / PD-L1 / TCR repertoire / alloresponse / direct recognition |
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| Outline of Final Research Achievements |
Here, we explored the role of CD4 T-cell-mediated alloresponses against endothelial HLA-DR in the presence of anti-HLA-class I or anti-A/B antibodies. CD4 T-cells, notably CD45RA-memory CD4 T-cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T-cell proliferative response was enhanced in the presence of anti-HLA-class I, but attenuated in the presence of anti-A/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed death-ligand 1 (PD-L1) increased in response to anti-A/B ligation in endothelial cells. Amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical/compatible transplants. Taken together, our findings identified a possible factors that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、Direct recognition pathwayに関わるCD4 T細胞の挙動とその重要性、DSAの影響について研究を行った。今後さらなる検討知見を得るためには、実際の移植臓器でのメカニズム解明が必要となる。特に実際の腎組織に浸潤しているT細胞の機能解析が必要になる、つまり、ABO不適合/適合腎移植において、腎組織でのPD-L1の高発現がどの程度の患者で確認できるのか、またその際に浸潤T細胞のサブセットに偏りが生じているのか。またそれらクローンは移植前に同定可能なのかどうかの研究を進めることで、免疫順応のメカニズム解明から治療法へとつながるはずである。
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