title: Synovial tissue-infiltrating natural killer cells in osteoarthritis and periprosthetic inflammation.
abstract: OBJECTIVE
  Infiltrating immune cells play a central role in degenerative joint disease associated with osteoarthritis (OA) and particle-mediated periprosthetic osteolysis. The goal of this study was to characterize a newly identified population of synovial tissue-infiltrating natural killer (NK) cells obtained from patients with OA or patients with periprosthetic joint inflammation.
  
  
  METHODS
  Synovial and interfacial tissue samples were collected from patients with OA who were undergoing primary or revision total joint replacement (TJR) surgery. The histologic features of OA synovium obtained from patients undergoing primary surgery and interfacial tissue obtained from patients undergoing revision surgery were determined by immunohistochemistry and immunofluorescence. Synovial tissue-infiltrating NK cells were evaluated for the expression of surface receptors, using flow cytometry. Chemoattractant and cytokine protein and RNA levels in synovial and interfacial tissue and fluid were assessed by Luminex assay and real-time quantitative polymerase chain reaction. Cytokine production and degranulation by stimulated synovial tissue versus normal blood NK cells were evaluated by intracellular cytokine staining.
  
  
  RESULTS
  NK cells comprised nearly 30% of the CD45+ mononuclear cell infiltrate in synovial tissue obtained from patients undergoing primary TJR and from patients undergoing revision TJR. NK cells from both groups expressed CXCR3, CCR5, L-selectin, α4 integrins, and cutaneous lymphocyte antigen. Synovial fluid from patients undergoing revision surgery contained elevated concentrations of the NK cell attractants CCL4, CCL5, CXCL9, and CXCL10; all levels in synovial fluid obtained from patients undergoing revision surgery were higher than those in synovial fluid from patients undergoing primary surgery. Cytokine-stimulated interferon-γ production was significantly impaired in NK cells derived from primary and revision TJRs compared with blood NK cells.
  
  
  CONCLUSIONS
  NK cells are a principal tissue-infiltrating lymphocyte subset in patients with OA and patients with periprosthetic inflammation and display a quiescent phenotype that is consistent with postactivation exhaustion.
authors.affiliation: Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Huss
authors.forename: James I
authors.initials: JI
authors.lastname: Huddleston
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
authors.forename: Brian A
authors.initials: BA
authors.lastname: Zabel
mesh_terms: D019643:Arthroplasty, Replacement; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007595:Joint Prosthesis / Q000009:adverse effects*; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D010014:Osteolysis / Q000473:pathology*; D012086:Reoperation; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; D016207:Cytokines; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens