HLA / A / B antibodies and endothelial cell responses that generate T cell subpopulation a new innovation in antibody-positive transplantation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11209
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Aichi Medical University
• Principal Investigator: Iwasaki Kenta 愛知医科大学, 医学部, 准教授 (10508881)
• 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)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 免疫順応 / 免疫寛容 / アロ応答 / PD-1/PD-L1

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.

Free Research Field

移植免疫

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。