title: Immunologic characterization of 3 murine regimens of allergen-specific immunotherapy.
abstract: BACKGROUND
  Allergen-specific immunotherapy (ASIT) is used to treat the symptoms of immediate type I hypersensitivity. The mechanisms driving establishment of allergen tolerance are not yet fully understood.
  
  
  OBJECTIVE
  The goal of this study was to develop and immunologically characterize 3 murine models of ASIT to simulate protocols currently used to treat patients with type I hypersensitivities.
  
  
  METHODS
  Ovalbumin (OVA)-sensitized mice were desensitized to OVA by means of repeated injections of OVA with a rapid, intermediate, or gradual protocol. After desensitization, mice were assessed for clinical sensitivity to OVA, and immunologic parameters were assessed.
  
  
  RESULTS
  Mice in all treatment protocols displayed decreased vascular permeability in response to OVA challenge after desensitization. Circulating OVA-specific IgE levels, as well as basophil activation in response to OVA stimulation and IgE cross-linking, were significantly decreased in all treatment groups. Intermediate and gradual protocols, but not rapid desensitization, suppressed splenocyte proliferation and production of IL-4, IL-5, and IFN-γ in response to OVA and polyclonal activation. Similarly, significant increases in IL-10 production, numbers of CD4(+)CD25(+) forkhead box protein 3-positive regulatory T cells, and OVA-specific IgG1 antibody levels were only observed in mice undergoing prolonged ASIT regimens.
  
  
  CONCLUSIONS
  Suppression of IgE-mediated activation is a common feature of all desensitization schedules. Induction of immunoregulatory networks requires prolonged desensitization schedules.
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Md.
authors.forename: Ellen Mueller
authors.initials: EM
authors.lastname: Fox
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Md.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Torrero
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Md.
authors.forename: Holly
authors.initials: H
authors.lastname: Evans
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University, Bethesda, Md. Electronic address: edward.mitre@usuhs.edu.
authors.forename: Edward
authors.initials: E
authors.lastname: Mitre
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D006969:Hypersensitivity, Immediate / Q000139:chemically induced / Q000276:immunology* / Q000628:therapy*; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D056747:Immunomodulation; D051379:Mice; D010047:Ovalbumin / Q000009:adverse effects; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D007132:Immunoglobulin Isotypes; D010047:Ovalbumin
keywords: Type I hypersensitivity; allergen-specific immunotherapy; basophils; mast cells; mouse models