Isolated late asthmatic reactions provoked by inhalation of T-cell peptide epitopes are associated with bronchial mucosal infiltration of CD4+ T cells and increased airway hyperresponsiveness☆

Abstract Rationale We previously demonstrated the induction of IgE-independent, MHC-restricted, isolated late asthmatic reactions (LARs) by intradermal (i.d.) administration of T-cell peptide epitopes derived from the major cat allergen, Fel d 1 (J Exp Med 1999;189:1885-94). A bronchoscopy study investigating i.d. peptide-induced LARs found neither cellular infiltration nor elevated concentrations of inflammatory mediators. We subsequently observed that inhalation of Fel d 1 peptides induced isolated LARs with associated sputum eosinophilia, suggesting that local peptide delivery might lead to more superficial changes. Methods A randomized, placebo-controlled, crossover study was performed involving bronchial biopsies and bronchoalveolar lavage fluids from 12 subjects who developed LARs 6 hours after Fel d 1 peptides inhalation (responders) and 12 subjects who showed no clinical response (non-responders). Histamine PC 20 was performed at baseline and 1 week after each challenge. Results Peptide-induced LARs were associated with a significant elevation in bronchial biopsy CD4+ count (p=0.034), whereas there was no change in non-responders. A trend towards increased total CD3+ cells was also observed (p=0.052), that was significantly different (p=0.005) from the non-responder group. A trend for increased eosinophils was noted in responders with Congo Red stain (p=0.064) and anti-MBP (p=0.067). No differences in cell numbers in BALF were identified. A significant increase in airway hyperreponsiveness was identified in responders 7 days after peptide challenge compared with diluent (p=0.001002), that was not seen in nonresponders (p=0.85). Conclusion Thus, inhalation of T-cell epitope peptides induces isolated LARs, associated with bronchial infiltration of CD4+ T-cells, and increased airway hyperresponsiveness, but only modest eosinophilia.