Kinetics and mode of peptide delivery via the respiratory mucosa determine the outcome of activation versus TH2 immunity in allergic inflammation of the airways

[摘要] Background: Specific immunotherapy involving systemic injection of allergen, though highly effective, can cause severe side effects due to IgE-mediated activation of effector cells. Allergen-derived peptides might provide a safer alternative. We have investigated the use of mucosally delivered peptide to induce CD4(+) T(H)2 cell tolerance and thus protect against allergen-induced airway inflammation. Objective: The purpose of this study was to investigate whether intranasal administration of an allergen-derived peptide, either alone or adsorbed to chitosan, can prevent the induction of T(H)2-mediated pulmonary inflammation after sensitization and challenge of the airways with allergen. Methods: Mice were given (intranasally) a peptide containing an inummodominant epitope of the Dermataphagoides pteronyssinus (Der p) 1 allergen, either as soluble antigen or adsorbed to chitosan, before sensitization and allergen challenge. Pulmonary inflammation, antigen-specific CD4+ T-cell responses, and antibody levels in sera were then determined. Results: Mice given peptide adsorbed to chitosan had significant reductions in airway eosinophilia, which correlated with reduced levels of IL-4 and IL-5 in the bronchoalveolar lavage fluid. There was decreased recruitment of activated CD4+ T cells into the airways after allergen challenge, which correlated with a loss of Der p 1-specific T-cell cytokine responses in the periphery and the localized production of IL-10 by antigen-specific T cells in bronchial lymph nodes. Induction of peripheral T-cell tolerance was preceded by transient T-cell activation and IFN-gamma production. Conclusion: Our data demonstrate that suppression of airway inflammation by intranasal administration of peptide antigen adsorbed to chitosan is initiated by transient T-cell activation and maintained by the production of IL-10 by antigen-specific T cells in the draining lymph nodes.

[发布日期] 2002-12-01

[关键词] allergy;tolerance;immunotherapy;in vivo animal models