Evaluation of degranulation and cytokine production in natural killer cells from spondyloarthritis patients at single-cell level (original) (raw)
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The involvement of NK cells in ankylosing spondylitis
International Immunology, 2005
A role for NK cells in the regulation of autoimmunity has been demonstrated. Since there is a strong association between Ankylosing Spondylitis (AS) and HLA-B27, which is specifically recognized by the NK-inhibitory receptor KIR3DL1, this study evaluated the potential involvement of NK cells in AS. We studied 19 AS patients and 22 healthy volunteer donors and assessed the percentage, activity and receptor expression of peripheral blood NK cells. We also evaluated candidate-inflammatory mediators in sera. We found that AS patients have significantly higher percentages of NK cells. However, we found no differences between the ability of NK cells derived from AS and healthy controls to recognize target cells expressing HLA-B27. Remarkably, we observed that the NK-inhibitory receptor CEACAM1 (carcino-embryonic antigen-cell adhesion molecule) is highly expressed among AS-derived NK cells. Furthermore, engagement of CEACAM1 inhibited NK activity in these patients. Finally, we demonstrated that CEACAM1 expression is induced by IL-8 and SDF-1 (stromal cell derived factor), both of which are present in high levels in the sera of AS patients. These results may indicate that NK cells and CEACAM1 play a role in AS pathogenesis and implicate chemokines in the mechanism of CEACAM1 expression.
Phenotypic study of natural killer cell subsets in ankylosing spondylitis patients
Iranian journal of allergy, asthma, and immunology, 2009
It has been demonstrated that natural killer (NK) cells play a role in regulation of autoimmunity. They play a protective role in several rodent disease models. In this study we aimed to compare the immunophenotypic features of NK cells in Ankylosing Spondylitis (AS) with normal subjects with regard to CD56 and CD16 molecules. This study was carried out on 30 AS patients and 33 normal volunteer donors. Peripheral Blood Mononuclear cells (PBMC) were tested by flow cytometry detecting the intensity of CD56 and CD16 surface molecules. The percentage of positive cells and their subsets were then calculated and statistically analyzed using SPSS software. A significant increase was found in CD56+ CD16+ (P < or = 0.009), and also in the subset of CD56 dim CD16+ (P < or = 0.02), but not in CD56 bright CD16+ (P=0.3) NK cells in AS patients compared to controls. We conclude that these results may indicate that NK and their subset ratios play a role in AS pathogenesis. Moreover, determin...
NK cells dysfunction in systemic lupus erythematosus: relation to disease activity
Clinical Rheumatology, 2013
Through their cytotoxic capacities and cytokine production, natural killer (NK) cells modulate autoimmune diseases. However, their role in the pathogenesis of systemic lupus erythematosus (SLE) has not been extensively studied. The aim of this study was to analyse the immunophenotypic and functional characteristics of the two major NK cell subsets in SLE and relate them with disease activity. Peripheral blood samples from 44 patients with active (n= 18) and inactive SLE (n=26) and 30 controls were analysed by flow cytometry to evaluate NK cell subsets, according to: the differential expression of CXCR3 and CD57; expression of granzyme B and perforin; and production of interferon gamma (IFN-γ) and tumor necrosis alpha (TNF-α), after PMA/ionomycin activation. A clear decrease in absolute and relative numbers of circulating NK cells was found in SLE, particularly in active disease, while the proportions of the major NK cell subsets were unaffected. Active SLE was associated with a reduced CXCR3 expression on both NK cell subsets and a lower frequency of CD56 dim NK cells expressing CXCR3. Furthermore, granzyme B expression was decreased in both SLE groups, but the percentage of NK cells expressing granzyme B and perforin was higher, particularly in active disease. We found a significant decrease in the percentage of CD56 bright and CD56 dim NK cells producing TNF-α and of its expression on CD56 dim NK cells in active disease, while IFN-γ expression on CD56 bright NK cells was increased in both SLE groups. Our findings suggest that NK cell subsets exhibit unique phenotypic and functional changes that are particularly evident in active SLE, and they may have the potential to affect the disease outcome.
RMD open, 2018
Ankylosing spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of human leucocyte antigen (HLA)-B27 alleles. HLA-E molecules are non-classical major histocompatibility complex (MHC) class I molecules that specifically interact with the natural killer receptors NKG2A (inhibitory) and NKG2C (activating), and have been recently proposed to be involved in AS pathogenesis.''. To analyse the expression of HLA-E and the CD94/NKG2 pair of receptors in HLA-B27-positive patients with AS and healthy controls (HC) bearing the AS-associated B*2705 and the non-AS-associated B*2709 alleles. The level of surface expression of HLA-E molecules on CD14+ peripheral blood mononuclear cell was evaluated in 21 HLA-B*2705 patients with AS, 12 HLA-B*2705 HC, 12 HLA-B*2709 HC and 6 HLA-B27-negative HC using the monoclonal antibody MEM-E/08 by quantitative cytofluorimetric analysis. The percentage and density of expression of HLA-E ligands NKG2A and NKG2C w...
Immunology, 2007
Natural killer (NK) cells are activated early during inflammatory events and contribute to the shaping of the ensuing adaptive immune response. To further understand the role for NK cells in inflammation, we investigated the phenotype and function of synovial fluid (SF) NK cells from patients with chronic joint inflammation, as well as from patients with transient inflammation of the knee following trauma. We confirm that synovial NK cells are similar to the well-characterized CD56 bright peripheral blood (PB) NK-cell subset present in healthy individuals. However, compared to this PB subset the synovial NK cells express a higher degree of activation markers including CD69 and NKp44, the latter being upregulated also on CD56 bright NK cells in the PB of patients. Activated synovial NK cells produced interferon-c and tumour necrosis factor, and the production was further up-regulated by antibody masking of CD94/ NKG2A, and down-regulated by target cells expressing human leucocyte antigen-E in complex with peptides known to engage CD94/NKG2A. We conclude that synovial NK cells have an activated phenotype and that CD94/NKG2A is a key regulator of synovial NK-cell cytokine synthesis.
PLoS ONE, 2011
Objective: TNF inhibitors (TNFi) have revolutionised the treatment of rheumatoid arthritis (RA). Natural killer (NK) cells and Natural Killer Cell Receptor + T (NKT) cells comprise important effector lymphocytes whose activity is tightly regulated through surface NK receptors (NKRs). Dysregulation of NKRs in patients with autoimmune diseases has been shown, however little is known regarding NKRs expression in patients with TNFi-induced remission and in those who maintain remission vs disease flare following TNFi withdrawal. Methods: Patients with RA were recruited for this study, (i) RA patients in clinical remission following a minimum of one year of TNFi therapy (n = 215); (2) Active RA patients, not currently or ever receiving TNFi (n = 18); and healthy control volunteers (n = 15). Patients in remission were divided into two groups: those who were maintained on TNFi and those who withdrew from TNFi and maintained on DMARDS. All patients underwent full clinical assessment. Peripheral blood mononuclear cells were isolated and NKR (CD94, NKG2A, CD161, CD69, CD57, CD158a, CD158b) expression on T-(CD3 + CD56 2), NK-(CD3 2 CD56 +) and NKT-(CD3 + CD56 +) cells was determined by flow cytometry. Results: Following TNFi withdrawal, percentages and numbers of circulating T cells, NK cells or NKT cell populations were unchanged in patients in remission versus active RA or HCs. Expression of the NKRs CD161, CD57, CD94 and NKG2A was significantly increased on CD3 + CD56-T cells from patients in remission compared to active RA (p,0.05). CD3 + CD56-T cell expression of CD94 and NKG2A was significantly increased in patients who remained in remission compared with patients whose disease flared (p,0.05), with no differences observed for CD161 and CD57. CD3 + CD56 2 cell expression of NKG2A was inversely related to DAS28 (r = 20.612, p,0.005). Conclusion: High CD94/NKG2A expression by T cells was demonstrated in remission patients following TNFi therapy compared to active RA, while low CD94/NKG2A were associated with disease flare following withdrawal of therapy.
Arthritis & Rheumatism, 2011
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 51 Cr release and CD107a degranulation experiments. Intracellular interferon-␥ (IFN␥) production by NK cells was evaluated after overnight stimulation with IL-12 and IL-18. IFN␣ levels were assessed using an antiviral cytopathic bioassay.