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Activating and inhibitory receptors on synovial fluid natural killer cells of arthritis patients: role of CD94/NKG2A in control of cytokine secretion
Authors:de Matos Cristina Teixeira  Berg Louise  Michaëlsson Jakob  Felländer-Tsai Li  Kärre Klas  Söderström Kalle
Affiliation:Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden. cristina.matos@ki.se
Abstract: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 up-regulated also on CD56(bright) NK cells in the PB of patients. Activated synovial NK cells produced interferon-gamma 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.
Keywords:autoimmunity   cell surface molecules   cytokines   inflammation   natural killer cells
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