NK1.1+ CD8+ T cells escape TGF-β control and contribute to early microbial pathogen response

Nat Commun. 2014 Oct 6;5:5150. doi: 10.1038/ncomms6150.

Abstract

Following microbial pathogen invasion, one of the main challenges for the host is to rapidly control pathogen spreading to avoid vital tissue damage. Here we report that an effector CD8(+) T-cell population that expresses the marker NK1.1 undergoes delayed contraction and sustains early anti-microbial protection. NK1.1(+) CD8(+) T cells are derived from CD8(+) T cells during priming, and their differentiation is inhibited by transforming growth factor-β signalling. After their own contraction phase, they form a distinct pool of KLRG1 CD127 double-positive memory T cells and rapidly produce both interferon-γ and granzyme B, providing significant pathogen protection in an antigen-independent manner within only a few hours. Thus, by prolonging the CD8(+) T-cell response at the effector stage and by expressing exacerbated innate-like features at the memory stage, NK1.1(+) cells represent a distinct subset of CD8(+) T cell that contributes to the early control of microbial pathogen re-infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / metabolism*
  • Bacterial Infections / immunology*
  • Bone Marrow Cells / cytology
  • CD8-Positive T-Lymphocytes / cytology*
  • Cell Differentiation
  • Female
  • Flow Cytometry
  • Granzymes / metabolism
  • Immunity, Innate
  • Immunologic Memory
  • Interferon-gamma / metabolism
  • Interleukin-15 / metabolism
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Listeria monocytogenes
  • Lymphocytic choriomeningitis virus
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NK Cell Lectin-Like Receptor Subfamily B / metabolism*
  • Peptides / chemistry
  • Phenotype
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism*
  • Virus Diseases / immunology*

Substances

  • Antigens, Ly
  • Interleukin-15
  • Interleukin-7 Receptor alpha Subunit
  • Klrb1c protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily B
  • Peptides
  • Transforming Growth Factor beta
  • Interferon-gamma
  • Granzymes