title: CD56negCD16⁺ NK cells are activated mature NK cells with impaired effector function during HIV-1 infection.
abstract: 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.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA. Jeffrey.Milush@ucsf.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Milush
authors.forename: Sandra
authors.initials: S
authors.lastname: López-Vergès
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: York
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
mesh_terms: D019011:Antigens, CD7 / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis*; D058851:GPI-Linked Proteins / Q000032:analysis; D053804:Granzymes / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D064368:Healthy Volunteers; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000032:analysis; D054353:Perforin / Q000096:biosynthesis; D017452:Receptors, IgG / Q000032:analysis*
chemical_list: D019011:Antigens, CD7; D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D052118:Lysosomal-Associated Membrane Protein 1; C522918:NCAM1 protein, human; D017452:Receptors, IgG; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes