Genetic fate mapping analysis of highly cytotoxic KLRG1+ effector CD8 T cells

• Project/Area Number: 16K19166
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Ishigame Harumichi 国立研究開発法人理化学研究所, 統合生命医科学研究センター, 研究員 (70729227)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: メモリーCD8T細胞 / 免疫記憶 / 分化可塑性 / エフェクターCD8T細胞 / メモリーCD8 T細胞 / 細菌感染 / 細胞運命追跡

Outline of Final Research Achievements

Protective immunity against pathogens depends on the efficient generation of functionally diverse effector and memory T lymphocytes. However, whether plasticity during effector-to-memory CD8+ T cell differentiation affects memory lineage specification and functional versatility remains unclear. Using genetic fate mapping analysis of highly cytotoxic KLRG1+ effector CD8+ T cells, we demonstrated that KLRG1+ cells receiving intermediate amounts of activating and inflammatory signals, downregulated KLRG1 during the contraction phase in a Bach2-dependent manner, and differentiated into all memory T cell linages, ‘ExKLRG1’ memory cells retained high cytotoxic and proliferative capacity distinct from other populations, which contributed to effective anti-influenza and anti-tumor immunity. Our work demonstrates that developmental plasticity of KLRG1+ effector CD8+ T cells is important in promoting functionally versatile memory cells and long-term protective immunity.

Research Products

• [Int'l Joint Research] Yale University School of Medicine(米国)
• [Journal Article] KLRG1+ effector CD8+ T cells lose KLRG1, differentiate into all memory T cell lineages, and convey enhanced protective immunity (2018)
  • Author(s): Dietmar Herndler-Brandstetter, Harumichi Ishigame, Ryo Shinnakasu, Valerie Plajer, Carmen Stecher, Jun Zhao, Melanie Lietzenmayer, Lina Kroehling, Akiko Takumi, Kohei Kometani, Takeshi Inoue, Yuval Kluger, Susan M. Kaech, Tomohiro Kurosaki, Takaharu Okada & Richard A. Flavell
  • Journal Title: Immunity Volume: 48(4) Issue: 4 Pages: 716-729
  • DOI: 10.1016/j.immuni.2018.03.015
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Developmental plasticity of KLRG1+ effector CD8+ T cells promotes protective immunity (2017)
  • Author(s): Harumichi Ishigame, Dietmar Herndler-Brandstetter, Ryo Shinnakasu, Kohei Kometani, Takeshi Inoue, Tomohiro Kurosaki, Takaharu Okada, Richard A. Flavell
  • Organizer: The 46th Annual Meeting of The Japanese Society for Immunology