[PDF][PDF] KLRG1+ effector CD8+ T cells lose KLRG1, differentiate into all memory T cell lineages, and convey enhanced protective immunity

D Herndler-Brandstetter, H Ishigame, R Shinnakasu… - Immunity, 2018 - cell.com
D Herndler-Brandstetter, H Ishigame, R Shinnakasu, V Plajer, C Stecher, J Zhao
Immunity, 2018cell.com
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 …
Summary
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, including CX3CR1int peripheral memory cells and tissue-resident memory cells. "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.
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