Phenotype and function of natural killer cells in systemic lupus erythematosus: excess interferon-γ production in patients with active disease

Arthritis Rheum. 2011 Jun;63(6):1698-706. doi: 10.1002/art.30313.


Objective: To determine the phenotype and the functionality of natural killer (NK) cells in patients with systemic lupus erythematosus (SLE).

Methods: A total of 94 patients with SLE (91 women and 3 men) were compared with 26 healthy controls. Active SLE was defined by an SLE Disease Activity Index score≥4. Immunologic tests were performed using nonactivated and/or interleukin-2 (IL-2)-activated peripheral blood mononuclear cells. NK cell phenotype was determined by flow cytometry. NK cell natural cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) were determined by 51Cr release and CD107a degranulation experiments. Intracellular interferon-γ (IFNγ) production by NK cells was evaluated after overnight stimulation with IL-12 and IL-18. IFNα levels were assessed using an antiviral cytopathic bioassay.

Results: The absolute NK cell count was decreased in patients with active SLE, but the relative frequencies of total CD3-CD56bright NK cells and CD3-CD56dim NK cells were unaffected. The CD3-CD56dim NK cells in patients with active SLE displayed unique phenotypic characteristics, including significant increases in CD69 and NKG2A and decreased expression of Fcγ receptor type IIIa/CD16, CD8α, and the killer cell immunoglobulin-like receptor (KIR) KIR2DL1/KIR2DS1. Concomitant with these findings, NK cells from SLE patients had lower cytotoxicity but a normal level of ADCC compared with NK cells from healthy controls. There was a significant positive correlation between the increased level of IFNα in the serum and the enhanced frequency of IFNγ+ cells in patients with active SLE (r=0.370, P=0.04).

Conclusion: NK cells in patients with active SLE display phenotypic and functional features associated with activation. Furthermore, NK cells from patients with active SLE have the capacity to produce large amounts of IFNγ. This could contribute to the dysregulation of the link between innate and adaptive immunity seen in SLE.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / immunology
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • CD3 Complex / immunology
  • CD56 Antigen / immunology
  • Female
  • GPI-Linked Proteins / immunology
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / immunology*
  • Interleukins / immunology
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type / immunology
  • Lupus Erythematosus, Systemic / immunology*
  • Lysosomal-Associated Membrane Protein 1 / immunology
  • Male
  • Middle Aged
  • Monocytes / immunology
  • NK Cell Lectin-Like Receptor Subfamily C / immunology
  • Phenotype
  • Receptors, IgG / immunology
  • Receptors, KIR / immunology
  • Severity of Illness Index
  • Young Adult


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD56 Antigen
  • CD69 antigen
  • FCGR3A protein, human
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Interleukins
  • Lectins, C-Type
  • Lysosomal-Associated Membrane Protein 1
  • NCAM1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily C
  • Receptors, IgG
  • Receptors, KIR
  • Interferon-gamma