induction of multi-functional regulatory T cell involved in maintenance of multiple sclerosis : application for vaccination of autoimmune diseases

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461301
• 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): 2013-04-01 – 2016-03-31
• Keywords: 制御性T細胞 / 抗原特異性 / 優位エピトープ / 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 / 再発と寛解

Outline of Final Research Achievements

Targeted monoclonal antibodies improved therapeutic efficacy in some autoimmune diseases, but it is insufficient for complete inhibition.
Focused on experimental autoimmune encephalomyelitis (EAE), we demonstrated that sensitization of superior dominant peptide sustained remission by inducing CD69+CD103+ (DP) subset of regulatory T cells (Treg). DP-subset of Treg was the most potent one, and possessed multiple hybrid signatures corresponding to each phase of EAE, stabilized with retention of the IL6R expression low. DP-subset obtained high antigen-specificity within hybrid signatures and IL6Rlow fraction, which required proper antigen stimulation for their maintenance. By limiting to its own, sensitization of superior dominant peptide could suppress the reactivity to other encephalitogenic peptides tissue-specifically, unlike tolerance-induction that inhibited just peptide-specifically. Such suppression was available even under EAE-undeveloped condition and in EAE-established mice.

Free Research Field

神経免疫学、免疫学