title: Anti-major histocompatibility complex-induced obliterative airway disease: selective role for CD4 and CD8 T cells in inducing immune responses to self-antigens.
abstract: BACKGROUND
  The goal of this study was to define the role of T-cell sub-sets in the pathogenesis of autoimmunity-induced obliterative airway disease by passive transfer of CD8+ or CD4+ T cells.
  
  
  METHODS
  Antibodies to major histocompatibility complex (MHC) class I were administered intrabronchially into C57BL/6 animals. Lungs were analyzed by histopathology and immunohistochemistry. The CD8+ and CD4+ T-cell sub-sets were purified from the lung-infiltrating cells and intrabronchially transferred. Frequency of cells secreting interleukin-17, interferon-γ, or interleukin-10 to self-antigens was enumerated by enzyme-linked immunospot assay. Myeloperoxidase and antibodies to self-antigens were determined by enzyme-linked immunosorbent assay. Cytokine and growth factor expression was determined by quantitative reverse-transcription polymerase chain reaction.
  
  
  RESULTS
  Passive transfer of lung-infiltrating CD8 T cells isolated after anti-MHC class I administration, along with sub-optimal dose, induced significantly higher cellular infiltration (89.3% ± 7.9% vs 62.8% ± 10.1%, p < 0.05) vs the CD4 transfer group. Further, passive transfer of CD8 cells resulted in infiltration of neutrophils and macrophages, suggesting early injury response. In contrast, passive transfer of CD4+ T cells induced a significantly higher degree of luminal occlusion (29.3% ± 5.6% vs 8.6 ± 2.5%, p < 0.05) and fibrosis (54.4% ± 9.3% vs 10.2% ± 2.4%, p < 0.05) vs the CD8 group and B-cell infiltration, leading to immune responses to lung-associated self-antigens and fibrosis.
  
  
  CONCLUSIONS
  Ligation of MHC molecules by its specific antibodies induced early injury with neutrophils, macrophages, and CD8 T cells, which leads to exposure of cryptic self-antigens and their presentation by the infiltrating CD4+ T cells and B cells, leading to the development of immune responses to self-antigens and culminating in obliterative airway disease.
authors: Departments of Surgery, ashington University School of Medicine, St Louis, Missouri 63110, USA.
authors: Venkataswarup
authors: V
authors: Tiriveedhi
authors: Masashi
authors: M
authors: Takenaka
authors: Nayan J
authors: NJ
authors: Sarma
authors: Andrew G
authors: AG
authors: Gelman
authors: Thalachallour
authors: T
authors: Mohanakumar
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001989:Bronchiolitis Obliterans / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001324:Autoantigens
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