title: An antigen-independent but not antigen-specific T(H)1 response provides protection in the murine airway inflammation model.
abstract: BACKGROUND
  Atopic disorders are associated with an imbalanced T(H) cell response biased toward a strong T(H)2 type, resulting in excessive production of IgE antibodies, eosinophil recruitment and activation, and mast cell degranulation. Restoring the T(H)1-T(H)2 balance by increasing the antigen-specific T(H)1 response has been pursued for specific allergy immunotherapy. Synthetic oligodeoxynucleotides containing unmethylated CG dinucleotides (CpG) are strong T(H)1 adjuvants and are being investigated for allergy immunotherapy.
  
  
  OBJECTIVE
  This study was designed to investigate the protective role of antigen-specific T(H)1 responses induced by epidermal powder immunization with ovalbumin (OVA) and CpG in a murine airway inflammation model.
  
  
  METHODS
  An allergy model was used in which BALB/c mice were sensitized and then challenged with OVA. Mice received prophylactic or therapeutic immunizations with OVA, CpG, or both. After challenge, pulmonary inflammation and cell infiltration were measured on the basis of BAL cell counts and lung histology. Immune response was determined by measuring the levels of lavage cytokines and serum antibodies.
  
  
  RESULTS
  Coadministration of OVA and CpG by means of subcutaneous injection or epidermal powder immunization, although inducing a strong T(H)1 response, neither suppressed T(H)2 cytokines nor offered protection against pulmonary eosinophilia and histopathology in a mouse challenge model. However, when CpG was used as a stand-alone treatment of previously sensitized animals, protection against allergic airway inflammation was observed. After challenge with OVA, eosinophilia was suppressed in the lungs of the CpG-treated mice.
  
  
  CONCLUSIONS
  This finding argues against the approach of boosting an allergen-dependent T(H)1 response and favors induction of an antigen-independent T(H)1 response for allergy immunotherapy.
authors.affiliation: PowderJect Vaccines, Inc., Seattle, WA, USA.
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Burger
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Zuleger
authors.forename: Qili
authors.initials: Q
authors.lastname: Chu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gao
authors.forename: Lendon G
authors.initials: LG
authors.lastname: Payne
authors.forename: Dexiang
authors.initials: D
authors.lastname: Chen
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004802:Eosinophilia / Q000517:prevention & control*; D005260:Female; D007114:Immunization; D008171:Lung Diseases / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D010047:Ovalbumin