Airway hyperresponsiveness and bronchial mucosal inflammation in T cell peptide-induced asthmatic reactions in atopic subjects

Ali, F. Runa; Kay, A. Barry; Larché, Mark
September 2007
Thorax;Sep2007, Vol. 62 Issue 9, p750
Academic Journal
Background: Subjects with allergic asthma develop isolated late asthmatic reactions after inhalation of allergen-derived T cell peptides. Animal experiments have shown that airway hyperresponsiveness (AHR) is CD4+ cell-dependent. It is hypothesised that peptide inhalation produces increases in non-specific AHR and a T cell-dominant bronchial mucosal inflammatory response. Methods: Bronchoscopy, with bronchial biopsies and bronchoalveolar lavage (BAL), was performed in 24 subjects with cat allergy 6 h after aerosol inhalation of short overlapping peptides derived from Fel d 1, the major cat allergen. Biopsy specimens and BAL fluid 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 Fe 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 thymus- and activation-regulated chemokine (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 =0.1 1). In BAL fluid there was a significant between- group difference in TARC (p=0.02) but not in histamine, tryptase, basogranulin, C3a or C5a, leukotrienes C4/D4/E4, prostaglandins D2 or F2α. Conclusions: Direct activation of allergen-specific airway T cells by peptide inhalation in patients with atopic asthma leads to increased AHR with local increases in CD3+ and CD4+ cells and TARC but no significant changes in eosinophils or basophil/mast cell products. These findings support previous animal experiments which showed a CD4+ dependence for AHR.


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