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

2017 Fiscal Year Final Research Report

• 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
• Keywords: メモリーCD8T細胞 / 免疫記憶 / 分化可塑性

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.

Free Research Field

免疫学