Anti-major histocompatibility complex-induced obliterative airway disease: Selective role for CD4 and CD8 T cells in inducing immune responses to self-antigens

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-gamma, 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 1 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. CONCLUSION: 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. J Heart Lung Transplant 2013;32:714-722 (C) 2013 International Society for Heart and Lung Transplantation. All rights reserved.