Opposite effects of immunotherapy with ovalbumin and the immunodominant T-cell epitope on airway eosinophilia and hyperresponsiveness in a murine model of allergic asthma

In the present study, we investigated immunotherapy using an entire protein or an immunodominant epitope in a murine model of allergic asthma. Immunot herapy was performed in ovalbumin (OVA)-sensitized mice before OVA challeng e. Mice were treated subcutaneously with OVA, the immunodominant epitope OV A(323-339), Or vehicle. In vehicle-treated animals, repeated OVA challenge induced increased serum levels of OVA-specific immunoglobulin (Ig)G1, IgE, airway eosinophilia, and hyperresponsiveness, compared with saline-challeng ed animals. In addition, interleukin (IL)-4 and IL-5 production upon OVA re stimulation of lung-draining lymph node cells in vitro were significantly i ncreased in OVA-challenged animals. Immunotherapy using OVA significantly r educed airway eosinophilia and hyperresponsiveness. This finding was accomp anied by significantly reduced OVA-specific IL-4 and IL-5 production. Furth er, OVA immunotherapy induced increased serum levels of OVA-specific IgG1, whereas OVA-specific IgG2a and IgE levels were not affected. In contrast to OVA immunotherapy, immunotherapy with OVA323-339 aggravated airway eosinop hilia and hyperresponsiveness. OVA-specific IgG1, IgG2a, and IgG serum leve ls, and in vitro IL-4 and IL-5 production, were not affected. Thus, immunot herapy with protein resulted in beneficial effects on airway eosinophilia a nd hyperresponsiveness, which coincided with a local reduced T-helper 2 (Th 2) response. In contrast, peptide immunotherapy aggravated airway hyperresp onsiveness and eosinophilia, indicating a local enhanced Th2 response.