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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cell Line, Tumor
  • Cell Lineage / immunology
  • Immunologic Memory / immunology*
  • Influenza A virus / immunology
  • Interleukin-12 Subunit p35 / immunology
  • Listeria monocytogenes / immunology
  • Lymphocyte Activation / immunology*
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Vesicular stomatitis Indiana virus / immunology

Substances

  • Bach2 protein, mouse
  • Basic-Leucine Zipper Transcription Factors
  • Il12a protein, mouse
  • Interleukin-12 Subunit p35
  • Klrg1 protein, mouse
  • Receptors, Immunologic