Inverse vaccination for autoimmune diseases and therapy for their chronic progression by multi-functional antigen-specific regulatory cell governing multiple sclerosis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09706
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Lin Youwei 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 免疫研究部, 併任研究員 (80392439)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 制御性Ｔ細胞 / 抗原特異性 / 脳炎惹起性ペプチド / 実験的自己免疫性脳脊髄炎 / 多発性硬化症 / 自己免疫ワクチン / 再発寛解維持 / 慢性進行抑制

Outline of Final Research Achievements

Targeted monoclonal antibodies improved therapeutic efficacy in some autoimmune diseases, but it is insufficient for complete inhibition.
We can induce different clinical course of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice with different encephalitogenic peptide, through different ability to induce CD69+CD103+ (DP) subset of regulatory T cells (Treg). DP-subset of Treg obtained high antigen-specificity within hybrid signatures, which was induced corresponding to multiple pathogenic T cells emerging at each phase of EAE and stabilized with proper antigen stimulation, and also exerted tissue repair capacity, resulting in complete inhibition of acute, relapse and progression of EAE.
The ability to induce DP-subset of Treg was correlated with the functional avidity of the sensitizing peptide, which was determined by the presence of its N- and C-terminal residues, and may contribute to the therapy for autoimmune diseases and also to optimization of anti-tumor immunity.

Free Research Field

神経免疫学、免疫学

Academic Significance and Societal Importance of the Research Achievements

免疫とは自己と非自己を区別し自己を防衛するシステムだが、その乱れで自己組織が障害される自己免疫疾患が生じる。病態解明の進歩により特定の分子を標的とした様々な薬剤が開発され画期的な効果を発揮しているものの、まだ完全に再発や進行を抑制できるものはなく、同じ標的をもつ他の疾患に応用できるとは限らない。
今回我々は脳炎惹起性ペプチドを感作して多発性硬化症と類似の病態を惹起する実験的自己免疫性脳脊髄炎(EAE)という動物モデルを利用し、ペプチドの長さを変更するだけで抗原特異的な制御性T細胞が誘導・維持され、EAEの再発・進行を完全に抑制できることを見いだし、上記の欠点を補うことができるのではないと考えた。