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Airway responsiveness and bronchial mucosal inflammation in T cell peptide-induced asthmatic reactions in atopic subjects
  1. Fawzia Runa Ali (j.m.mitchell{at}imperial.ac.uk)
  1. Imperial College London, United Kingdom
    1. Anthony Barrington Kay (j.m.mitchell{at}imperial.ac.uk)
    1. Imperial College London, United Kingdom
      1. Mark Larche (larche{at}mcmaster.ca)
      1. McMaster University, Canada

        Abstract

        Background: Allergic asthmatics develop isolated late asthmatic reactions after inhalation of allergen- derived T-cell peptides. Animal experiments have shown that airway hyperresponsiveness is CD4+ cell-dependent. We hypothesise that peptide inhalation produces increases in non-specific airway hyperresponsiveness (AHR) and a T-cell dominant, bronchial mucosal inflammatory response.

        Methods: Bronchoscopy, with bronchial biopsies and bronchoalveolar lavage (BAL), was performed in 24 cat-allergic subjects 6 hours after aerosol inhalation of short overlapping peptides derived from Fel d 1, the major cat allergen. Biopsies and BAL were studied using immunohistochemistry and ELISA.

        Results: Twelve of the 24 subjects developed an isolated late asthmatic reaction without a preceding early- (mast cell/histamine-dependent) reaction characteristic of whole allergen inhalation. These responders had a significant between-group differences (responders vs non-responders) in the changes (peptide vs diluent) in AHR (p= 0.007) and bronchial mucosal CD3+ (p=0.005), CD4+ (p=0.006) and TARC+ (p=0.003) but not CD8+ or CD25+ cells or eosinophils, basophils, mast cells and macrophages. The between-group difference for neutrophils was p=0.05 but with a non-significant within group value (peptide vs diluent, responders, p=0.11). In BAL there was a significant between-group difference in TARC (p=0.02) but not in histamine, tryptase, basogranulin, C3a or C5a, LTC4/D4/E4, PGD2 or PGF2α.

        Conclusions: Direct activation of allergen- specific airway T cells by peptide inhalation in atopic asthmatics leads to increased airway hyperresponsiveness with local increases in CD3+ and CD4+ cells and TARC but no significant changes in eosinophils or basophil/mast cell products thereby supporting previous animal experiments which showed a CD4+ dependence for airway hyperresponsiveness.

        • T cells
        • airway hyperresponsiveness
        • cytokines
        • late asthmatic reactions
        • peptides

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