Interruption of CD28-mediated costimulation during allergen challenge protects mice from allergic airway disease

• Published in: Journal of allergy and clinical immunology 2012-12, Vol.130 (6), p.1394-1403.e4
• Main Authors: Gogishvili, Tea, Dr rer nat, Lühder, Fred, Dr rer nat, Kirstein, Frank, PhD, Nieuwenhuizen, Natalie E., PhD, Goebbels, Sandra, Dr rer nat, Beer-Hammer, Sandra, Dr rer nat, Pfeffer, Klaus, MD, Reuter, Sebastian, Dr rer nat, Taube, Christian, MD, Brombacher, Frank, PhD, Hünig, Thomas, Dr rer nat
• Format: Article
• Language: English
• Subjects: Airway management; Allergens; Allergic asthma; Allergies; Allergy and Immunology; Animal models; Animals; Antibodies, Blocking - administration & dosage; Antibodies, Monoclonal - administration & dosage; Antigens, Dermatophagoides - immunology; Asthma; Biological and medical sciences; CD28 antigen; CD28 Antigens - genetics; CD28 Antigens - immunology; CD28 Antigens - metabolism; CD28-specific mAb; CD4 antigen; Chronic obstructive pulmonary disease, asthma; conditional CD28 knockout mice; costimulation; Disease Models, Animal; Experiments; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Helper cells; Humans; Immunoglobulin E; Immunopathology; Inflammation; Ligands; Lung; Lymphocyte Activation - drug effects; Lymphocyte Activation - genetics; Lymphocyte Count; Lymphocytes; Lymphocytes T; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Monoclonal antibodies; Ovalbumin; Ovalbumin - immunology; Pneumology; Proteins; Receptor Cross-Talk - drug effects; Respiratory Hypersensitivity - immunology; Respiratory Hypersensitivity - therapy; Respiratory tract diseases; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; T cell receptors; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Th2 Cells - drug effects; Th2 Cells - immunology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2012.08.049

Background Allergic asthma is a TH 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 TH 2 but not TH 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. Conclusion Selective interference with CD28-mediated costimulation during allergen exposure might be an attractive therapeutic concept for allergic asthma.