title: Proliferatory defect of invariant population and accumulation of non-invariant CD1d-restricted natural killer T cells in the joints of RA patients.
abstract: OBJECTIVE
  While numerical and functional defects of invariant NKT cells have been demonstrated in rheumatoid arthritis (RA), the detailed characterization of proliferative and secretory responses following CD1d-mediated presentation is lacking; the presence of non-invariant populations has never been assessed in human autoimmunity. We have evaluated both invariant and non-invariant populations in the blood and synovial fluid from patients to assess feasibility of NKT cell-directed manipulations in RA.
  
  
  METHODS
  NKT cell populations were quantified by anti-CD4/anti-Vα24 staining and/or CD1d tetramers. Proliferation was measured in cultures of mononuclear cells following stimulations with αGalCer and cytokine secretion determined by multi-bead assay.
  
  
  RESULTS
  We have confirmed a proliferative defect of iNKT cells in both peripheral blood and synovial fluid from RA patients, but no changes in baseline frequencies. Moreover, we have detected an enlargement of non-invariant cell pool in synovial fluid samples. In addition, we noted an evident Th2 shift following exposure to αGalCer and pronounced IL-6 secretion.
  
  
  CONCLUSIONS
  While RA patients suffer from defective proliferative responses of invariant NKT cells, non-invariant cells accumulate at the site of inflammation. While stimulation with αGalCer results in reduced TNF-α and increased suppressive IL-10, abundantly produced IL-6 could potentially contribute to the induction of Th17 cells in the joints.
authors.affiliation: Department of Rheumatology, Inflammation Research Unit , School of Clinical Sciences, University of Liverpool , UK.
authors.forename: Danuta
authors.initials: D
authors.lastname: Gutowska-Owsiak
authors.forename: Martin A
authors.initials: MA
authors.lastname: Birchall
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Moots
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Christmas
authors.forename: Laszlo
authors.initials: L
authors.lastname: Pazmany
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007596:Joints / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D016207:Cytokines