The development of novel desensitization therapy for transplant patients with donor specific HLA antibody.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Hiroshima University
• Principal Investigator: Ide Kentaro 広島大学, 病院(医), 講師 (50511565)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 臓器移植 / 抗体関連型拒絶反応

Outline of Final Research Achievements

In this study, we investigated the effect of anti-CD20 mAb -mediated B-cell depletion on anti-donor T-cell responses and the inhibitory role of B-cells in a highly sensitized transplant model. The average stimulation index values for CD4+ T-cell responses to donor stimulation were significantly higher in the desensitization group than those in the control group. When co-cultured with various B-cells in the CFSE-MLR assay of the desensitization group, the addition of whole CD19+ B-cells and B1-cells significantly suppressed the anti-donor CD4+ T-cell responses. However, the addition of non B1-cells did not suppress the anti-donor CD4+ T-cell responses. These findings demonstrate that B-cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T-cell responses in a highly sensitized transplant model. It might be possible that the sensitized CD5+ CD19+ B1-cells have an ability to inhibit anti-donor CD4+ T-cell responses.

Free Research Field

臓器移植

Academic Significance and Societal Importance of the Research Achievements

高感作移植患者は抗体関連型拒絶反応のハイリスク群であるため、移植適応が厳しく制限されている。我々はこのような患者に対する脱感作療法を独自に考案し、DSAの産生を制御し移植を可能とさせたが、本脱感作療法施行後には抗ドナーT細胞応答の亢進を来し、細胞性拒絶反応発症の危険性を高めるため、プロトコールの更なる改良が望まれている。本研究により抗ドナーT細胞応答亢進の機序が解明されたため、従来移植困難とされていた患者への適応拡大や移植後の生着率向上に貢献できる