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

6533b857fe1ef96bd12b3b3e

RESEARCH PRODUCT

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

Fred Lühder Fred Lühder Natalie E. Nieuwenhuizen Frank Brombacher Klaus Pfeffer Thomas Hünig Sandra Beer-hammer Frank Kirstein Tea Gogishvili Christian Taube Sebastian Reuter Sandra Goebbels

subject

Allergic asthma Lymphocyte Activation Immunoglobulin E medicine.disease_cause T-Lymphocytes Regulatory Mice 0302 clinical medicine Airway resistance Allergen Immunology and Allergy Sensitization Mice Inbred BALB C 0303 health sciences biology Antibodies Monoclonal ovalbumin respiratory system 3. Good health medicine.anatomical_structure costimulation conditional CD28 knockout mice Female medicine.symptom Immunology Inflammation 03 medical and health sciences Th2 Cells CD28 Antigens Respiratory Hypersensitivity medicine Animals Humans Antigens Dermatophagoides Lymphocyte Count Antibodies Blocking 030304 developmental biology House dust mite CD28-specific mAb business.industry Receptor Cross-Talk Airway obstruction medicine.disease biology.organism_classification Mice Mutant Strains respiratory tract diseases Disease Models Animal CTLA-4 Immunology biology.protein business 030215 immunology

description

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. Conclusion Selective interference with CD28-mediated costimulation during allergen exposure might be an attractive therapeutic concept for allergic asthma.

year	journal	country	edition	language
2012-12-31

10.1016/j.jaci.2012.08.049 https://doi.org/10.1016/j.jaci.2012.08.049