CD56negCD16⁺ NK cells are activated mature NK cells with impaired effector function during HIV-1 infection

Retrovirology. 2013 Dec 18;10:158. doi: 10.1186/1742-4690-10-158.


Background: A subset of CD3(neg)CD56(neg)CD16⁺ Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations.

Results: Using CD7 as an additional NK cell marker, we found that CD3(neg)CD56(neg)CD16⁺ cells are a heterogeneous population comprised of CD7⁺ NK cells and CD7(neg) non-classical myeloid cells. CD7⁺CD56(neg)CD16⁺ NK cells are significantly expanded in HIV-1 infection. CD7⁺CD56(neg)CD16⁺ NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to CD7⁺CD56⁺CD16⁺ NK cells. CD7⁺CD56(neg) NK cells in healthy donors produced minimal IFNγ following K562 target cell or IL-12 plus IL-18 stimulation; however, they degranulated in response to K562 stimulation similar to CD7⁺CD56⁺ NK cells. HIV-1 infection resulted in reduced IFNγ secretion following K562 or cytokine stimulation by both NK cell subsets compared to healthy donors. Decreased granzyme B and perforin expression and increased expression of CD107a in the absence of stimulation, particularly in HIV-1-infected subjects, suggest that CD7⁺CD56(neg)CD16⁺ NK cells may have recently engaged target cells. Furthermore, CD7⁺CD56(neg)CD16⁺ NK cells have significantly increased expression of CD95, a marker of NK cell activation.

Conclusions: Taken together, CD7⁺CD56(neg)CD16⁺ NK cells are activated, mature NK cells that may have recently engaged target cells.

Publication types

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

MeSH terms

  • Antigens, CD7 / analysis
  • CD56 Antigen / analysis*
  • GPI-Linked Proteins / analysis
  • Granzymes / biosynthesis
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Healthy Volunteers
  • Humans
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / chemistry*
  • Killer Cells, Natural / immunology*
  • Lysosomal-Associated Membrane Protein 1 / analysis
  • Perforin / biosynthesis
  • Receptors, IgG / analysis*


  • Antigens, CD7
  • CD56 Antigen
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Lysosomal-Associated Membrane Protein 1
  • NCAM1 protein, human
  • Receptors, IgG
  • Perforin
  • Interferon-gamma
  • Granzymes