title: CD28 negative T cells are enriched in granulomatous lesions of the respiratory tract in Wegener's granulomatosis.
abstract: BACKGROUND
  Lack of CD28 expression on peripheral blood CD4+ and CD8+ T cells has been reported in patients with Wegener's granulomatosis (WG), suggesting a pathogenetic role of CD28- T cells in WG.
  
  
  METHODS
  Ten patients with WG and six with sarcoidosis (disease control) were analysed. Fluorescence activated cell sorter (FACS) analysis was used to detect CD28 expression on T cells from peripheral venous blood and from bronchoalveolar lavage (BAL) fluid. T cells in biopsy specimens from granulomatous lesions of the upper respiratory tract were analysed for CD28 expression by double immunofluorescence staining.
  
  
  RESULTS
  A significantly higher fraction of CD28- T cells was found in the CD4+ and CD8+ T cell compartment in BAL fluid (65.6 (5.4)% and 76.3 (4.1)%, respectively) than in blood (13.4 (6.2)% and 42.9 (6.2)%; p<0.001) in patients with WG but not in those with acute sarcoidosis (6.7 (2.2)% and 53.4 (7.3)% in BAL fluid v 4.1 (2.5)% and 52.0 (9.4)% in blood). The total number of CD4+/CD28- T cells but not of CD8+/CD28- T cells was also significantly higher in BAL fluid than in blood in patients with WG (p<0.05). Patients with WG had a significantly higher fraction of CD28- T cells in the CD4+ and CD8+ T cell compartment in BAL fluid than patients with acute sarcoidosis (65.6 (5.4)% v 6.7 (2.2)%; p<0.001; and 76.3 (4.1)% v 53.4 (7.3)%; p<0.05). The total number of CD4+/CD28- and CD8+/CD28- T cells was also significantly higher in patients with WG than in those with sarcoidosis (p<0.01). An abundance of CD28- T cells was found in granulomatous lesions by double immunofluorescence staining in patients with WG.
  
  
  CONCLUSIONS
  Our data indicate enrichment of CD28- T cells in BAL fluid and suggest recruitment of CD28- T cells into granulomatous lesions in WG. Further analysis of the phenotype and function of T cell subsets in WG is needed to better understand leucocyte homing in WG and to find new therapeutic targets.
authors.affiliation: Department of Rheumatology, University of Luebeck, 23538 Luebeck, Germany. gross@medinf.mu-luebeck.de
authors.forename: P
authors.initials: P
authors.lastname: Lamprecht
authors.forename: F
authors.initials: F
authors.lastname: Moosig
authors.forename: E
authors.initials: E
authors.lastname: Csernok
authors.forename: U
authors.initials: U
authors.lastname: Seitzer
authors.forename: A
authors.initials: A
authors.lastname: Schnabel
authors.forename: A
authors.initials: A
authors.lastname: Mueller
authors.forename: W L
authors.initials: WL
authors.lastname: Gross
mesh_terms: D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D014890:Granulomatosis with Polyangiitis / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D008875:Middle Aged; D012507:Sarcoidosis / Q000276:immunology; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018106:CD28 Antigens