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.
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 SLEpatients 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.
Authors: Roberto Spada; José M Rojas; Sonia Pérez-Yagüe; Vladimir Mulens; Pablo Cannata-Ortiz; Rafael Bragado; Domingo F Barber Journal: J Leukoc Biol Date: 2015-01-12 Impact factor: 4.962
Authors: K Hudspeth; S Wang; J Wang; S Rahman; M A Smith; K A Casey; Z Manna; M Sanjuan; R Kolbeck; S Hasni; R Ettinger; R M Siegel Journal: Clin Exp Immunol Date: 2019-03-19 Impact factor: 4.330
Authors: Shereen Oon; Huy Huynh; Tsin Yee Tai; Milica Ng; Katherine Monaghan; Mark Biondo; Gino Vairo; Eugene Maraskovsky; Andrew D Nash; Ian P Wicks; Nicholas J Wilson Journal: JCI Insight Date: 2016-05-05