Airway hyperresponsiveness and bronchial mucosal inflammation in T cell peptide-induced asthmatic reactions in atopic subjects
- Departments of Allergy and Clinical Immunology and Leukocyte Biology, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, NHLI Division, Imperial College, London, UK
- Correspondence to:
Professor A B Kay
Leukocyte Biology Section, Sir Alexander Fleming Building, South Kensington Campus, Imperial College, London SW7 2AZ, UK;
- Received 21 September 2006
- Accepted 6 February 2007
- Published Online First 27 March 2007
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 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 = 0.11). 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.
- AHR, airway hyperresponsiveness
- BAL, bronchoalveolar lavage
- CGRP, calcitonin gene-related peptide
- FEV1, forced expiratory volume in 1 s
- histamine PC20, histamine provocative concentration causing a 20% fall in FEV1
- IL, interleukin
- LAR, late asthmatic reaction
- LT, leukotriene
- MBP, major basic protein
- PEFR, peak expiratory flow rate
- PG, prostaglandin
- TARC, thymus- and activation-regulated chemokine
Published Online First 27 March 2007
This study was supported by the Medical Research Council (UK) and Asthma UK.
Competing interests: ABK and ML have shares in Circassia Holdings.