Development of Inhibitory method specific for activated T cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K19576
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Pathology, Infection/Immunology, and related fields
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Saito Takashi 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (50205655)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: STING / T細胞 / 増殖抑制 / 活性化シグナル / mTORC1 / IFN-g

Outline of Final Research Achievements

Aberrantly activated T cells induce autoimmune and allergic diseases. So far, all immunosuppressive drugs work on all T cells, and the method to specifically inhibit activated T cells is desired. When T cells were stimulated with STING ligand, cGAMP together with antigen, growth inhibition was induced only on activated T cells. cGAMP stimulation induces inhibition of mTOR activation, leading to growth inhibition of T cells. On the other hand, cGAMP stimulation induces positively type I-IFN from T cells. Direct stimulation of T cells by cGAMP innoculation in vivo augments of anti-tumor immunity

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

特異抗原で活性化されたT細胞を特異的に抑制する方法はこれまでなかったが、少なくともin vitroでは、活性化T細胞を抗原とともにSTINGを共刺激すれば、特異的なT細胞増殖抑制が誘導されることがわかり、自己免疫疾患やアレルギーなど異常に活性化されたT細胞を抑制できる方法開発の端緒についた。一方同時にSTING刺激でT細胞から自然免疫を凌ぐ大量なI型IFNが産生され、in vivo投与によってcGAMPは抗腫瘍活性を亢進できることが判明し、I型IFNによる制御に新しい局面を開いた。