title: The immune cell composition in Barrett's metaplastic tissue resembles that in normal duodenal tissue.
abstract: OBJECTIVE
  Barrett's esophagus (BE) is characterized by the transition of squamous epithelium into columnar epithelium with intestinal metaplasia. The increased number and types of immune cells in BE have been indicated to be due to a Th2-type inflammatory process. We tested the alternative hypothesis that the abundance of T-cells in BE is caused by a homing mechanism that is found in the duodenum.
  
  
  METHODS
  Biopsies from BE and duodenal tissue from 30 BE patients and duodenal tissue from 18 controls were characterized by immmunohistochemistry for the presence of T-cells and eosinophils(eos). Ex vivo expanded T-cells were further phenotyped by multicolor analysis using flowcytometry.
  
  
  RESULTS
  The high percentage of CD4(+)-T cells (69±3% (mean±SEM/n = 17, by flowcytometry)), measured by flowcytometry and immunohistochemistry, and the presence of non-activated eosinophils found in BE by immunohistochemical staining, were not different from that found in duodenal tissue. Expanded lymphocytes from these tissues had a similar phenotype, characterized by a comparable but low percentage of αE(CD103) positive CD4(+)cells (44±5% in BE, 43±4% in duodenum of BE and 34±7% in duodenum of controls) and a similar percentage of granzyme-B(+)CD8(+) cells(44±5% in BE, 33±6% in duodenum of BE and 36±7% in duodenum of controls). In addition, a similar percentage of α4β7(+) T-lymphocytes (63±5% in BE, 58±5% in duodenum of BE and 62±8% in duodenum of controls) was found. Finally, mRNA expression of the ligand for α4β7, MAdCAM-1, was also similar in BE and duodenal tissue. No evidence for a Th2-response was found as almost no IL-4(+)-T-cells were seen.
  
  
  CONCLUSIONS
  The immune cell composition (lymphocytes and eosinophils) and expression of intestinal adhesion molecule MAdCAM-1 is similar in BE and duodenum. This supports the hypothesis that homing of lymphocytes to BE tissue is mainly caused by intestinal homing signals rather than to an active inflammatory response.
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lind
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Kusters
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Van der Linden
authors.forename: Edward F
authors.initials: EF
authors.lastname: Knol
authors.forename: Leo
authors.initials: L
authors.lastname: Koenderman
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001471:Barrett Esophagus / Q000276:immunology* / Q000473:pathology*; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules; D004386:Duodenum / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D039001:Integrin alpha Chains / Q000378:metabolism; D039441:Integrin alpha4 / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D008297:Male; D008679:Metaplasia / Q000276:immunology; D008875:Middle Aged; D009088:Mucoproteins / Q000235:genetics; D009092:Mucous Membrane / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D012333:RNA, Messenger; C091367:alpha E integrins; C091368:integrin beta7; D039441:Integrin alpha4; D053804:Granzymes