Antigen-specific immunoglobulin-A prevents increased airway responsiveness and lung eosinophilia after airway challenge in sensitized mice.

Aeroallergens such as Amb a I from short ragweed are important in the development of allergic airway disease. We tested the ability of a human monoclonal immunoglobulin-A (IgA) antibody specific for Amb a I (A-IgA) to modulate airway responsiveness and lung eosinophilia after airway challenge with nebulized Amb a I or ragweed extract in mice sensitized to Amb a I or ragweed extract, respectively. A-IgA or nonspecific IgA (C-IgA) were given intranasally up to 8 h before each challenge. Allergen challenge resulted in increases in airway responsiveness, in numbers of lung eosinophils, and in Amb a I-specific IgE levels. These were prevented by pretreatment with A-IgA but not with C-IgA. Decreases in IFN-gamma and increases in IL-4 and IL-5 production following challenge with Amb a I were also reduced by A-IgA treatment. In contrast, increases in total IgE and total IgG and in numbers of lung neutrophils after challenge were not significantly affected by A-IgA, which additionally induced increased levels of Amb a I-specific IgG2a antibodies. In mice sensitized and challenged with ovalbumin (OVA), A-IgA did not affect airway responsiveness, lung eosinophilia, cytokine production, or immunoglobulin levels. These data indicate that allergen-specific IgA can prevent airway hyperresponsiveness and reduce eosinophil influx into the lungs following allergen challenge via the airways in sensitized mice, and these effects are allergen-specific. Neutralization of allergen may contribute to the effects of IgA, but the induction of allergen-specific IgG2a in A-IgA-treated mice suggests an immunomodulatory action for A-IgA.