Cutting edge: identification and characterization of human intrahepatic CD49a+ NK cells

J Immunol. 2015 Mar 15;194(6):2467-71. doi: 10.4049/jimmunol.1402756. Epub 2015 Feb 11.


Although NK cells are considered innate, recent studies in mice revealed the existence of a unique lineage of hepatic CD49a(+)DX5(-) NK cells with adaptive-like features. Development of this NK cell lineage is, in contrast to conventional NK cells, dependent on T-bet but not Eomes. In this study, we describe the identification of a T-bet(+)Eomes(-)CD49a(+) NK cell subset readily detectable in the human liver, but not in afferent or efferent hepatic venous or peripheral blood. Human intrahepatic CD49a(+) NK cells express killer cell Ig-like receptor and NKG2C, indicative of having undergone clonal-like expansion, are CD56(bright), and express low levels of CD16, CD57, and perforin. After stimulation, CD49a(+) NK cells express high levels of inflammatory cytokines but degranulate poorly. CD49a(+) NK cells retain their phenotype after expansion in long-term in vitro cultures. These results demonstrate the presence of a likely human counterpart of mouse intrahepatic NK cells with adaptive-like features.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD56 Antigen / immunology
  • CD56 Antigen / metabolism
  • Cell Proliferation*
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism
  • Flow Cytometry
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Integrin alpha1 / immunology*
  • Integrin alpha1 / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Liver / immunology*
  • Liver / metabolism
  • NK Cell Lectin-Like Receptor Subfamily C / immunology
  • NK Cell Lectin-Like Receptor Subfamily C / metabolism
  • Receptors, IgG / immunology
  • Receptors, IgG / metabolism
  • Receptors, KIR / immunology
  • Receptors, KIR / metabolism


  • CD56 Antigen
  • Cytokines
  • Inflammation Mediators
  • Integrin alpha1
  • KIR2DS1 protein, human
  • KLRC2 protein, human
  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, IgG
  • Receptors, KIR