T-cell-mediated inflammation does not contribute to the maintenance of airway dysfunction in mice

1 Firestone Institute for Respiratory Health, Department of Medicine, and 2 Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada L8N 4A6 Submitted 16 June 2004 ; accepted in final form 27 July 2004 T-cell-mediated airway inflammation is considered to be critical in the pathogenesis of airway hyperresponsiveness (AHR). We have described a mouse model in which chronic allergen exposure results in sustained AHR and aspects of airway remodeling and here sought to determine whether eliminating CD4 + and CD8 + cells, at a time when airway remodeling had occurred, would attenuate this sustained AHR. Sensitized BALB/c mice were subjected to either brief or chronic periods of allergen exposure and studied 24 h after brief or 4 wk after chronic allergen exposure. In both models, mice received three treatments with anti-CD4 and -CD8 monoclonal antibodies during the 10 days before outcome measurements. Outcomes included in vivo airway responsiveness to intravenous methacholine, CD4 + and CD8 + cell counts of lung and spleen using flow cytometric analysis, and airway morphometry using a computer-based image analysis system. Compared with saline control mice, brief allergen challenge resulted in AHR, which was eliminated by antibody treatment. Chronic allergen challenge resulted in sustained AHR and indexes of airway remodeling. This sustained AHR was not reversed by antibody treatment, even though CD4 + and CD8 + cells were absent in lung and spleen. These results indicate that T-cell-mediated inflammation is critical for development of AHR associated with brief allergen exposure, but is not necessary to maintain sustained AHR. allergy; lung; T lymphocytes; rodent; bronchial hyperreactivity Address for reprint requests and other correspondence: M. D. Inman, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, 50 Charlton Ave. East, Hamilton, Ontario, Canada L8N 4A6 (E-mail: inmanma{at}mcmaster.ca )