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

Immunity | 2018

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.

Pubmed ID: 29625895 RIS Download

Antibodies used in this publication

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI074699
  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG008383
  • Agency: NIAID NIH HHS, United States
    Id: R37 AI066232
  • Agency: Howard Hughes Medical Institute, United States

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R Project for Statistical Computing (tool)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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GraphPad Prism (tool)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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Picard (tool)

RRID:SCR_006525

Java toolset for working with next generation sequencing data in the BAM format.

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BACH2 antibody (antibody)

RRID:AB_1861444

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Actin (C-11) (antibody)

RRID:AB_630835

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RFP Antibody Biotin Conjugated Pre-adsorbed (antibody)

RRID:AB_828390

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RFP Antibody Pre-adsorbed (antibody)

RRID:AB_2209751

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APC anti-T-bet (antibody)

RRID:AB_10896913

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FITC anti-mouse NK-1.1 (antibody)

RRID:AB_313392

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Ki-67 (antibody)

RRID:AB_10611874

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APC anti-mouse Ki-67 (antibody)

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PE/Cyanine7 anti-mouse IL-2 (antibody)

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RRID:AB_313369

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APC anti-mouse Ly-6G/Ly-6C (Gr-1) (antibody)

RRID:AB_313377

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RRID:AB_2563147

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Biotin anti-mouse CX3CR1 (antibody)

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PE/Cyanine7 anti-mouse CX3CR1 (antibody)

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FITC anti-mouse CX3CR1 (antibody)

RRID:AB_2565703

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FITC anti-mouse CD103 (antibody)

RRID:AB_10714791

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FITC anti-mouse CD69 (antibody)

RRID:AB_313109

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FITC anti-mouse/human CD44 (antibody)

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Biotin anti-mouse CD11c (antibody)

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CD11b (antibody)

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CD8a (antibody)

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PerCP anti-mouse CD8a (antibody)

RRID:AB_893423

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PE anti-mouse CD8a (antibody)

RRID:AB_312747

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Biotin anti-mouse CD4 (antibody)

RRID:AB_312711

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CD4 (antibody)

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