title: Interruption of CD28-mediated costimulation during allergen challenge protects mice from allergic airway disease.
abstract: BACKGROUND
  Allergic asthma is a T(H)2-promoted hyperreactivity with an immediate, IgE, and mast cell-dependent response followed by eosinophil-dominated inflammation and airway obstruction.
  
  
  OBJECTIVE
  Because costimulation by CD28 is essential for T(H)2 but not T(H)1 responses, we investigated the effect of selective interference with this pathway in mice using the models of ovalbumin and house dust mite-induced airway inflammation.
  
  
  METHODS
  To study the role of CD28 in the effector phase of allergic airway inflammation, we developed an inducibly CD28-deleting mouse strain or alternatively used a CD28 ligand-binding site-specific mouse anti-mouse mAb blocking CD28 engagement.
  
  
  RESULTS
  We show that even after systemic sensitization to the allergen, interruption of CD28-mediated costimulation is highly effective in preventing airway inflammation during challenge. In addition to improving airway resistance and histopathologic presentation and reducing inflammatory infiltrates, antibody treatment during allergen challenge resulted in a marked relative increase in regulatory T-cell numbers among the CD4 T-cell subset of the challenged lung.
  
  
  CONCLUSIONS
  Selective interference with CD28-mediated costimulation during allergen exposure might be an attractive therapeutic concept for allergic asthma.
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
authors.forename: Tea
authors.initials: T
authors.lastname: Gogishvili
authors.forename: Fred
authors.initials: F
authors.lastname: Lühder
authors.forename: Frank
authors.initials: F
authors.lastname: Kirstein
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Nieuwenhuizen
authors.forename: Sandra
authors.initials: S
authors.lastname: Goebbels
authors.forename: Sandra
authors.initials: S
authors.lastname: Beer-Hammer
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Reuter
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: Thomas
authors.initials: T
authors.lastname: Hünig
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D039741:Antigens, Dermatophagoides / Q000276:immunology; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology; D020239:Receptor Cross-Talk / Q000187:drug effects; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D039741:Antigens, Dermatophagoides; D018106:CD28 Antigens; D010047:Ovalbumin