Journal Article
. 2018 Apr; 48(4):716-729.e8.
doi: 10.1016/j.immuni.2018.03.015.

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

Dietmar Herndler-Brandstetter 1 Harumichi Ishigame 2 Ryo Shinnakasu 3 Valerie Plajer 1 Carmen Stecher 1 Jun Zhao 4 Melanie Lietzenmayer 1 Lina Kroehling 1 Akiko Takumi 5 Kohei Kometani 6 Takeshi Inoue 7 Yuval Kluger 8 Susan M Kaech 1 Tomohiro Kurosaki 3 Takaharu Okada 9 Richard A Flavell 10 
  • PMID: 29625895
  •     60 References
  •     118 citations


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.

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J Immunol, 2020 Jul 03; 205(4). PMID: 32611727    Free PMC article.
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Markus Flosbach, Susanne G Oberle, +11 authors, Dietmar Zehn.
Cell Rep, 2020 Jul 30; 32(4). PMID: 32726622    Free PMC article.
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Front Bioeng Biotechnol, 2020 Aug 28; 8. PMID: 32850698    Free PMC article.
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J Immunol, 2020 Jul 17; 205(4). PMID: 32669309    Free PMC article.
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Cells, 2020 Nov 15; 9(11). PMID: 33187162    Free PMC article.
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Front Immunol, 2020 Dec 03; 11. PMID: 33262762    Free PMC article.
MEK inhibition reprograms CD8+ T lymphocytes into memory stem cells with potent antitumor effects.
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Nat Immunol, 2020 Nov 25; 22(1). PMID: 33230330
The JAK1 Selective Inhibitor ABT 317 Blocks Signaling Through Interferon-γ and Common γ Chain Cytokine Receptors to Reverse Autoimmune Diabetes in NOD Mice.
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Front Immunol, 2020 Dec 22; 11. PMID: 33343569    Free PMC article.
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A Combination of Anti-PD-L1 Treatment and Therapeutic Vaccination Facilitates Improved Retroviral Clearance via Reactivation of Highly Exhausted T Cells.
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Nat Immunol, 2020 May 20; 21(7). PMID: 32424367
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The Extracellular ATP Receptor P2RX7 Imprints a Promemory Transcriptional Signature in Effector CD8+ T Cells.
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