Airway hyperresponsiveness and bronchial mucosal inflammation in T cell peptide-induced asthmatic reactions in atopic subjects.
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 C(4)/D(4)/E(4), prostaglandins D(2) or F(2alpha).


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.
Ali
F Runa
FR
Department of Allergy and Clinical Immunology, Imperial College, London, UK.
Kay
A Barry
AB
Larché
Mark
M
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000503:physiopathology; D001991:Bronchitis / Q000276:immunology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D001999:Bronchoscopy / Q000379:methods; D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D016207:Cytokines