Chemokine Receptor Expression on Normal Blood CD56(+) NK-Cells Elucidates Cell Partners That Comigrate during the Innate and Adaptive Immune Responses and Identifies a Transitional NK-Cell Population

J Immunol Res. 2015;2015:839684. doi: 10.1155/2015/839684. Epub 2015 Oct 12.


Studies of chemokine receptors (CKR) in natural killer- (NK-) cells have already been published, but only a few gave detailed information on its differential expression on blood NK-cell subsets. We report on the expression of the inflammatory and homeostatic CKR on normal blood CD56(+low) CD16(+) and CD56(+high) CD16(-/+low) NK-cells. Conventional CD56(+low) and CD56(+high) NK-cells present in the normal PB do express CKR for inflammatory cytokines, although with different patterns CD56(+low) NK-cells are mainly CXCR1/CXCR2(+) and CXCR3/CCR5(-/+), whereas mostly CD56(+high) NK-cells are CXCR1/CXCR2(-) and CXCR3/CCR5(+). Both NK-cell subsets have variable CXCR4 expression and are CCR4(-) and CCR6(-). The CKR repertoire of the CD56(+low) NK-cells approaches to that of neutrophils, whereas the CKR repertoire of the CD56(+high) NK-cells mimics that of Th1(+) T cells, suggesting that these cells are prepared to migrate into inflamed tissues at different phases of the immune response. In addition, we describe a subpopulation of NK-cells with intermediate levels of CD56 expression, which we named CD56(+int) NK-cells. These NK-cells are CXCR3/CCR5(+), they have intermediate levels of expression of CD16, CD62L, CD94, and CD122, and they are CD57(-) and CD158a(-). In view of their phenotypic features, we hypothesize that they correspond to a transitional stage, between the well-known CD56(+high) and CD56(+low) NK-cells populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Adult
  • Antigens, Surface / metabolism
  • CD56 Antigen / metabolism*
  • Cytokines / metabolism
  • Female
  • Humans
  • Immunity, Innate*
  • Immunophenotyping
  • Inflammation Mediators / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Male
  • Middle Aged
  • Phenotype
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • Young Adult


  • Antigens, Surface
  • CD56 Antigen
  • Cytokines
  • Inflammation Mediators
  • Receptors, Chemokine