title: Opposite effects of immunotherapy with ovalbumin and the immunodominant T-cell epitope on airway eosinophilia and hyperresponsiveness in a murine model of allergic asthma.
abstract: 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 OVA323-339, 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 OVA323-339 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.
authors.affiliation: Department of Pharmacology and Pathophysiology, Faculty of Pharmacy, Institute of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: Janssen
authors.forename: M H
authors.initials: MH
authors.lastname: Wauben
authors.forename: E H
authors.initials: EH
authors.lastname: Jonker
authors.forename: G
authors.initials: G
authors.lastname: Hofman
authors.forename: W
authors.initials: W
authors.lastname: Van Eden
authors.forename: F P
authors.initials: FP
authors.lastname: Nijkamp
authors.forename: A J
authors.initials: AJ
authors.lastname: Van Oosterhout
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004802:Eosinophilia / Q000276:immunology / Q000628:therapy*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016056:Immunodominant Epitopes / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007167:Immunotherapy; D007249:Inflammation / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology*; D012130:Respiratory Hypersensitivity / Q000628:therapy*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
chemical_list: D016207:Cytokines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin