CD56brightCD16+ NK cells: a functional intermediate stage of NK cell differentiation

J Immunol. 2011 Jun 15;186(12):6753-61. doi: 10.4049/jimmunol.1100330. Epub 2011 May 9.


Human NK cells comprise two main subsets, CD56(bright) and CD56(dim) cells, which differ in function, phenotype, and tissue localization. To further dissect the differentiation from CD56(bright) to CD56(dim) cells, we performed ex vivo and in vitro experiments demonstrating that the CD56(bright)CD16(+) cells are an intermediate stage of NK cell maturation. We observed that the maximal frequency of the CD56(bright)CD16(+) subset among NK cells, following unrelated cord blood transplantation, occurs later than this of the CD56(bright)CD16(-) subset. We next performed an extensive phenotypic and functional analysis of CD56(bright)CD16(+) cells in healthy donors, which displayed a phenotypic intermediary profile between CD56(bright)CD16(-) and CD56(dim)CD16(+) NK cells. We also demonstrated that CD56(bright)CD16(+) NK cells were fully able to kill target cells, both by Ab-dependent cell cytotoxicity (ADCC) and direct lysis, as compared with CD56(bright)CD16(-) cells. Importantly, in vitro differentiation experiments revealed that autologous T cells specifically encourage the differentiation from CD56(bright)CD16(-) to CD56(bright)CD16(+) cells. Finally, further investigations performed in elderly patients clearly showed that both CD56(bright)CD16(+) and CD56(dim)CD16(+) mature subsets were substantially increased in older individuals, whereas the CD56(bright)CD16(-) precursor subset was decreased. Altogether, these data provide evidence that the CD56(bright)CD16(+) NK cell subset is a functional intermediate between the CD56(bright) and CD56(dim) cells and is generated in the presence of autologous T CD3(+) cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CD3 Complex
  • CD56 Antigen / analysis*
  • Cell Differentiation / immunology*
  • Cord Blood Stem Cell Transplantation
  • GPI-Linked Proteins / immunology
  • Humans
  • Immunophenotyping
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology
  • Receptors, IgG / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Tissue Donors


  • CD3 Complex
  • CD56 Antigen
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Receptors, IgG