Activating and inhibitory receptors on synovial fluid natural killer cells of arthritis patients: role of CD94/NKG2A in control of cytokine secretion.
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.
de Matos
Cristina Teixeira
CT
Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden. cristina.matos@ki.se
Berg
Louise
L
Michaëlsson
Jakob
J
Felländer-Tsai
Li
L
Kärre
Klas
K
Söderström
Kalle
K
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D007718:Knee Injuries / Q000276:immunology; D007719:Knee Joint / Q000276:immunology; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000276:immunology*; D020370:Osteoarthritis, Knee / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D013582:Synovial Fluid / Q000276:immunology*; D000097625:HLA-E Antigens
D016207:Cytokines; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C527054:KLRC1 protein, human