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Immunity. 2018 Apr 17;48(4):716-729.e8. doi: 10.1016/j.immuni.2018.03.015. Epub 2018 Apr 3.

KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity.

Author information

1
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
2
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan. Electronic address: harumichi.ishigame@riken.jp.
3
Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
4
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Pathology, Yale University School of Medicine, New Haven, CT 06511, USA; Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.
5
Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
6
Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
7
Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
8
Department of Pathology, Yale University School of Medicine, New Haven, CT 06511, USA; Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA; Applied Mathematics Program, Yale University, New Haven, CT 06511, USA.
9
Laboratory for Tissue Dynamics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan; Graduate School of Medical Life Science, Yokohama City University, Yokohama, Kanagawa 230-0045, Japan. Electronic address: takaharu.okada@riken.jp.
10
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: richard.flavell@yale.edu.

Abstract

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.

KEYWORDS:

Bach2; CD8 T cell; CX(3)CR1; cancer; fate mapping; inflammation; influenza; memory; plasticity; tissue-resident

PMID:
29625895
PMCID:
PMC6465538
DOI:
10.1016/j.immuni.2018.03.015
[Indexed for MEDLINE]
Free PMC Article

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