title: Increased T-cell survival by structural bronchial cells derived from asthmatic subjects cultured in an engineered human mucosa.
abstract: BACKGROUND
  Interaction between lymphocytes and structural cells has been proposed as a key factor in regulating inflammation in asthma.
  
  
  OBJECTIVE
  This study was designed to investigate the effect of epithelial cells and fibroblasts on T-lymphocyte survival by using a 3-dimensional tissue-engineered model.
  
  
  METHODS
  Engineered human bronchial mucosal tissues were produced by using fibroblasts, epithelial cells, and autologous T cells from asthmatic and healthy donors. T-cell apoptosis and apoptotic marker expression by T cells were evaluated by using the terminal deoxynucleotidyl transferase biotinylated d-UTP nick end-labeling technique and immunofluorescence, respectively. Cytokines implicated in T-cell survival were measured by means of ELISA in culture supernatants.
  
  
  RESULTS
  We demonstrated histologically that we were able to generate a well-structured engineered bronchial mucosa by using epithelial cells, fibroblasts, and T cells cultured from healthy and asthmatic subjects. Structural cells from asthmatic subjects cultured in this model induced a significant decrease in the ability of T cells to undergo apoptosis represented by a decrease in DNA fragmentation and proapoptotic molecule expression (Bcl-2-associated X protein and Fas ligand). Structural cells from healthy control subjects have no effect. Among cytokines measured in the supernatants, only TGF-beta(1) was significantly increased in the model derived from cells of asthmatic subjects.
  
  
  CONCLUSIONS
  These results support the concept that bronchial structural cells might play a critical role in the regulation of inflammation in asthma by increasing the survival of T lymphocytes. The results also further validated the model as a tool for investigating the interaction between inflammatory and structural cells.
authors.affiliation: Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumology, Laval, Quebec, Canada.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Darveau
authors.forename: Eric
authors.initials: E
authors.lastname: Jacques
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Rouabhia
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
authors.forename: Jamila
authors.initials: J
authors.lastname: Chakir
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000166:cytology / Q000276:immunology; D002450:Cell Communication / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D020287:In Situ Nick-End Labeling; D020545:Respiratory Mucosa; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis
chemical_list: D053773:Transforming Growth Factor beta1