title: The CD14(bright) CD16+ monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population.
abstract: OBJECTIVE
  Circulating monocytes contain a subpopulation of CD14+CD16+ cells; this subpopulation of cells has been described to be proinflammatory and to have an increased frequency in rheumatoid arthritis (RA). New evidence suggests that this subpopulation can be further subdivided into CD14(dim) CD16+ and CD14(bright) CD16+ cells. The aim of this study was to determine which of the two CD16+ monocyte subpopulations is expanded in patients with RA and to investigate their possible role in disease pathogenesis.
  
  
  METHODS
  The frequencies of monocyte subpopulations in the peripheral blood of healthy donors and patients with RA were determined by flow cytometry. Monocyte subpopulations were sorted and cocultured with CD4+ T cells. Cytokines were determined in the supernatant, and Th17 cell frequencies were measured by flow cytometry.
  
  
  RESULTS
  In comparison with the other monocyte subpopulations, CD14(bright) CD16+ cells showed higher HLA-DR and CCR5 expression and responded with higher tumor necrosis factor production to direct cell contact with preactivated T cells. They were observed at increased frequencies in the peripheral blood of patients with RA, while CD14(dim) CD16+ monocyte frequencies were not increased. CD14(bright) CD16+ cells were extremely potent inducers of Th17 cell expansion in vitro. Their frequency in the peripheral blood of patients with RA correlated closely with Th17 cell frequencies determined ex vivo.
  
  
  CONCLUSIONS
  This study is the first to provide a link between the increased frequency of the CD14(bright) CD16+ monocyte subpopulation in RA and the expansion of Th17 cells, which are likely to have a role in the pathogenesis of autoimmunity.
authors: Division of Rheumatology, Department of Internal Medicine, University of Leipzig, Leipzig, Germany. manuela.rossol@medizin.uni-leipzig.de
authors: Manuela
authors: M
authors: Rossol
authors: Stephan
authors: S
authors: Kraus
authors: Matthias
authors: M
authors: Pierer
authors: Christoph
authors: C
authors: Baerwald
authors: Ulf
authors: U
authors: Wagner
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D002454:Cell Differentiation; D002469:Cell Separation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007958:Leukocyte Count; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019713:Receptors, CCR5 / Q000032:analysis; D017452:Receptors, IgG / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D019713:Receptors, CCR5; D017452:Receptors, IgG; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate