title: Squamous tissue lymphocytes in the esophagus of controls and patients with reflux esophagitis and Barrett's esophagus are characterized by a non-inflammatory phenotype.
abstract: OBJECTIVE
  Reflux esophagitis (RE) is characterized by inflammation of the squamous epithelium (SQ) of the esophagus and may progress to Barrett's esophagus (BE) characterized by intestinal metaplasia. The role of inflammation in this transition has been postulated but lacks experimental evidence. Here, the inflammatory responses in the esophagus of these patients were investigated.
  
  
  METHODS
  Fifty-one esophageal biopsies from with patients BE (n = 19), RE (n = 8) and controls (n = 23) were analyzed. T-cells were analyzed before and after ex vivo expansion (14 days) by multicolor flow cytometric analysis. The following markers were studied: CD3, CD4, CD8 (T-cell markers), Granzyme B (marker of cytotoxicity), CD103 (αE/epithelial integrin) and NKg2a (inhibitory receptor on T-cells and NK-cells).
  
  
  RESULTS
  Analysis of ex vivo cultures from normal looking SQ from controls, RE patients, and BE patients revealed no significant differences in the number and phenotypes of T-cells. In contrast, tissue from RE was different to normal SQ in four aspects: 1) higher percentages of CD3+ CD4+-cells (72±7% vs 48±6%, p = 0.01) and 2) CD8+ GranzymeB+-cells (53±11% vs 26±4%, p<0.05), while 3) lower percentages of CD4+ CD103+-cells (45±19% vs 80±3%, p = 0.02) and 4) CD8+ NKg2a+-cells (31±12% vs 44±5%).
  
  
  CONCLUSIONS
  Despite the fact that both tissues are exposed to the same reflux associated inflammatory triggers, the immune response observed in RE is clearly distinct from that in SQ of BE. The differences in immune responses in BE tissue might contribute to its susceptibility for transformation into intestinal metaplasia.
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lind
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Kusters
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
mesh_terms: D000328:Adult; D000368:Aged; D000943:Antigens, Differentiation / Q000276:immunology; D001471:Barrett Esophagus / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D004941:Esophagitis / Q000276:immunology* / Q000473:pathology; D004947:Esophagus / Q000276:immunology* / Q000473:pathology; D005764:Gastroesophageal Reflux / Q000276:immunology / Q000473:pathology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged
chemical_list: D000943:Antigens, Differentiation