title: Human allogeneic CD2+ lymphocytes activate airway-derived epithelial cells to produce interleukin-6 and interleukin-8. Possible role for the epithelium in chronic allograft rejection.
abstract: BACKGROUND
  The adhesion of lymphocytes to the epithelium and the release of proinflammatory cytokines are important features observed during acute and chronic allograft rejection. Development of chronic rejection in lung-transplantation patients is preceded by high levels of interleukin (IL)-6 and IL-8 protein in the bronchoalveolar lavage. Therefore, we studied the expression of IL-6 and IL-8 in cocultures of epithelial cells and allogeneic lymphocytes.
  
  
  METHODS
  IL-6 and IL-8 protein levels were determined in supernatants of the airway-derived epithelial cell line A549 and in primary epithelial cells obtained from lung-brushings after coculturing with autologous and allogeneic lymphocytes. Transcriptional mechanisms were detected by transient transfections.
  
  
  RESULTS
  Coculture-supernatants of epithelial cells and allogeneic CD2+ lymphocytes show high levels of IL-6 and IL-8 protein due to transcriptional activation of the respective genes in epithelial cells. Highest productions were measured when the epithelial-cell:lymphocyte ratio was 1:10. Highly purified CD4+ and/or CD8+ cells were unable to induce the same response as observed with the total lymphocyte-population. Depletion of CD4+ and/or CD8+ had no effect on the IL-6 and IL-8 production induced by the total CD2+ lymphocyte-population. However, depletion of CD56+ cells diminished the lymphocyte-induced IL-6 and IL-8 production by > 75%.
  
  
  CONCLUSIONS
  These data show that allogeneic CD2+ lymphocytes are able to activate lung-derived epithelial cells, resulting in the release of proinflammatory cytokines, which have a prominent role in chronic allograft rejection observed in lung-transplantation patients.
authors: Department of Pathology and Clinical Medicine, Division of Allergology, and Pulmonology, University Hospital Groningen, Groningen, The Netherlands. p.borger@path.azg.nl
authors: P
authors: P
authors: Borger
authors: H F
authors: HF
authors: Kauffman
authors: J
authors: J
authors: Scholma
authors: J A B
authors: JA
authors: Timmerman
authors: G H
authors: GH
authors: Koëter
mesh_terms: D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology*; D016040:Lung Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8