Developing a novel therapeutic strategy to infectious disease based on innate immune function of T lymphocytes

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19418
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Tohoku University
• Principal Investigator: Kawabe Takeshi 東北大学, 医学系研究科, 准教授 (50834652)
• Co-Investigator(Kenkyū-buntansha): 石井 直人 東北大学, 医学系研究科, 教授 (60291267)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: T細胞 / 恒常性 / 感染免疫 / 自己免疫疾患

Outline of Final Research Achievements

CD4 T lymphocytes play an essential role in adaptive immunity. Within this population, we reported a novel “memory-phenotype” (MP) cell subpopulation that possesses innate immune function in pathogen infection. Based on this finding, we aimed to identify phenotypic markers of MP cells and reveal their immunological significance in host defense as well as autoimmunity. In this study, we found that CD127, Sca1, and Bcl2 are differentially expressed by MP vs. foreign antigen-specific memory cells and that MP cells themselves can be divided into four subpopulations depending on the marker expression. Furthermore, we defined innate immune function as well as autoimmune activities of the CD127(hi) Sca1(hi) MP subset (Front Immunol 2022). Together these results suggest CD127(hi) Sca1(hi) MP cells as a potential therapeutic target in infectious disease by deliberately activating their innate immune activities.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により、MP細胞がCD127、Sca1発現により4分画に分類されること、うちCD127(hi) Sca1(hi) MP分画が最も強い自然免疫活性ならびに自己免疫活性を有することが明らかになった。今後、同分画の活性化機構や免疫学的機能の全容が明らかになれば、MP細胞を人為的に活性化することによる新たな感染症治療戦略「免疫賦活化治療」（JMA J 2022）の創出、抑制による新たな自己免疫・炎症性疾患治療法の提唱などにつながり得るものと期待される。