Am. J. Respir. Cell Mol. Biol., Volume 21, Number 1, July, 1999 21-29

Opposite Effects of Immunotherapy with Ovalbumin and the Immunodominant T-Cell Epitope on Airway Eosinophilia and Hyperresponsiveness in a Murine Model of Allergic Asthma

Edith M. Janssen, Marca H. M. Wauben, Eline H. Jonker, Gerard Hofman, Willem Van Eden, Frans P. Nijkamp, and Antoon J. M. Van Oosterhout

Department of Pharmacology and Pathophysiology, Faculty of Pharmacy; and Institute of Infectious Diseases and Immunology, Department of Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

In the present study, we investigated immunotherapy using an entire protein or an immunodominant epitope in a murine model of allergic asthma. Immunotherapy was performed in ovalbumin (OVA)-sensitized mice before OVA challenge. Mice were treated subcutaneously with OVA, the immunodominant epitope OVA_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-challenged animals. In addition, interleukin (IL)-4 and IL-5 production upon OVA restimulation of lung-draining lymph node cells in vitro were significantly increased in OVA-challenged animals. Immunotherapy using OVA significantly reduced airway eosinophilia and hyperresponsiveness. This finding was accompanied by significantly reduced OVA-specific IL-4 and IL-5 production. Further, 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 OVA_323-339 aggravated airway eosinophilia and hyperresponsiveness. OVA-specific IgG1, IgG2a, and IgE serum levels, and in vitro IL-4 and IL-5 production, were not affected. Thus, immunotherapy with protein resulted in beneficial effects on airway eosinophilia and hyperresponsiveness, which coincided with a local reduced T-helper 2 (Th2) response. In contrast, peptide immunotherapy aggravated airway hyperresponsiveness and eosinophilia, indicating a local enhanced Th2 response.

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