OBJECTIVE: To determine whether natural killer (NK) cells are present within inflamed joints and whether they might play a role in amplifying the inflammatory process. METHODS: Paired samples of peripheral blood and synovial fluid were obtained from 22 patients with inflammatory arthritis. The frequency and phenotype of the peripheral and synovial NK cells were analyzed using a panel of monoclonal antibodies. Further experiments were performed to investigate the functional capacity of the synovial NK cells. RESULTS: The study showed that the CD3-, CD56(bright) subset of NK cells was greatly expanded within inflamed joints. Our experiments suggested that this subset of cells was preferentially recruited from the periphery and that NK cells may be further activated by cytokines present within the joint. Furthermore, synovial NK cells responded to a combination of interleukin-12 (IL-12) and IL-15, cytokines that are secreted by cells of the monocyte/macrophage lineage, by rapidly secreting interferon-gamma, a cytokine that can, in turn, activate macrophages. CONCLUSION: A subset of NK cells was expanded within inflamed joints. The functional properties of these NK cells rendered them good candidates for a role in interacting with the macrophage/monocyte population within the joint, thus amplifying the production of proinflammatory cytokines.
OBJECTIVE: To determine whether natural killer (NK) cells are present within inflamed joints and whether they might play a role in amplifying the inflammatory process. METHODS: Paired samples of peripheral blood and synovial fluid were obtained from 22 patients with inflammatory arthritis. The frequency and phenotype of the peripheral and synovial NK cells were analyzed using a panel of monoclonal antibodies. Further experiments were performed to investigate the functional capacity of the synovial NK cells. RESULTS: The study showed that the CD3-, CD56(bright) subset of NK cells was greatly expanded within inflamed joints. Our experiments suggested that this subset of cells was preferentially recruited from the periphery and that NK cells may be further activated by cytokines present within the joint. Furthermore, synovial NK cells responded to a combination of interleukin-12 (IL-12) and IL-15, cytokines that are secreted by cells of the monocyte/macrophage lineage, by rapidly secreting interferon-gamma, a cytokine that can, in turn, activate macrophages. CONCLUSION: A subset of NK cells was expanded within inflamed joints. The functional properties of these NK cells rendered them good candidates for a role in interacting with the macrophage/monocyte population within the joint, thus amplifying the production of proinflammatory cytokines.
Authors: M Das; J Lu; M Joseph; R Aggarwal; S Kanji; B K McMichael; B S Lee; S Agarwal; A Ray-Chaudhury; O H Iwenofu; P Kuppusamy; V J Pompili; M K Jain; H Das Journal: Curr Mol Med Date: 2012-02 Impact factor: 2.222
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