Development of a cell therapy for autoimmune diseases using monoclonal T cells specific for one target antigen

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02668
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Kyoto University
• Principal Investigator: kawamoto hiroshi 京都大学, ウイルス・再生医科学研究所, 教授 (00343228)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 制御性T細胞 / 自己免疫疾患 / 関節リウマチモデル / sk gマウス / RPL23a

Outline of Final Research Achievements

In this study, we tried to develop a new method by which autoimmune diseases can be cured using a monoclonal T cells with single antigen specificity. It has been reported that the monoclonal helper T cells expressing TCR (R7-39) specific for target antigen originally identified as a causative antigen of arthritis and dermatitis in skg mouse. Therefore, in this study, we produced regulatory T cells (Treg) that monoclonally express TCR (R7-39) and tested whether these cells exert therapeutic effect on the desiase model described above. We found that, although adaptive transfer of these cells were not effective for arthritis, these cells showed efficacy in reducing the severity of dermatitis. This can be said as a first demonstration in the world that showed treatment of disease by using Treg. Some planned experiments were not necessarily completed as originally designed, but we can say that a significant results were obtained during the study period.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患の治療は、免疫抑制剤や抗サイトカイン抗体などで免疫を非特異的に抑制するという方法が現在も主流であり、従って感染症などの副作用が避けられない。このような状況を打開するためには、抗原特異的な治療法で特定の標的抗原に対する免疫反応だけを抑えて病気を治す必要がある。本研究はそのような方法の開発に取り組んだ先進的な取り組みであった。その結果として、単一クローンのヘルパーT細胞で誘導できる皮膚炎が、同じ抗原特異性を持つ単一クローン制御性T細胞の投与により症状を軽減できることが示された。制御性T細胞による発症予防の報告は多くあるが、治療例としては世界初であると考えている。