ASTHMA

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

F Runa Ali, A Barry Kay, Mark Larché

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; a.b.kay{at}imperial.ac.uk

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 F₂.

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.

Abbreviations: 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

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