Variation of human natural killer cell phenotypes with age: identification of a unique KLRG1-negative subset

Hum Immunol. 2010 Jul;71(7):676-81. doi: 10.1016/j.humimm.2010.03.014. Epub 2010 Apr 23.


Human natural killer (NK) cells subsets are phenotypically characterized by their lack of CD3 and low/high expression of CD56. This study revealed an age-associated increase in the ratio of CD3(-)CD56(dim) to CD3(-)CD56(bright) NK cells, whereas distinct expression patterns of CD2, CD16, CD57, and the C-type lectin family members killer cell lectin-like receptor -D1 (CD94) and -G1 (KLRG1), were noted on both these NK and the CD3(+)CD56(+) T cell subsets; moreover, CD94 and KLRG1 expression were significantly reduced with age. Although the proportion of CD3(-)CD56(bright) NK cells vs CD3(-)CD56(dim) cells decreased with age, the percentage of CD3(-)CD56(bright) cells expressing IFN-gamma after activation significantly increased, potentially representing compensatory augmentation of cytokine production to maintain the important immunoregulatory role of these cells in older individuals. Collectively, these results highlight new evidence for a continuum of change during immunologic aging and present unique data for variation of NK cell subsets with human aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD3 Complex / metabolism
  • CD56 Antigen / metabolism
  • Cell Count
  • Humans
  • Immunophenotyping
  • Interferon-gamma / metabolism
  • Interleukin-15 / pharmacology
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / metabolism
  • Lectins, C-Type / metabolism*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Lymphocyte Subsets / cytology*
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / metabolism
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Middle Aged
  • Receptors, Immunologic
  • Trans-Activators / metabolism*
  • Young Adult


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD56 Antigen
  • CD69 antigen
  • Interleukin-15
  • KLRG1 protein, human
  • Lectins, C-Type
  • Lysosomal-Associated Membrane Protein 1
  • Receptors, Immunologic
  • Trans-Activators
  • Interferon-gamma