Interruption of CD28-mediated costimulation during allergen challenge protects mice from allergic airway disease - 28/11/12
, Fred Lühder, Dr rer nat a, b, , Frank Kirstein, PhD g, Natalie E. Nieuwenhuizen, PhD g, Sandra Goebbels, Dr rer nat c, Sandra Beer-Hammer, Dr rer nat d, Klaus Pfeffer, MD e, Sebastian Reuter, Dr rer nat f, Christian Taube, MD h, Frank Brombacher, PhD g, Thomas Hünig, Dr rer nat a, ⁎ 
Corresponding author: Thomas Hünig, Dr rer nat, Institute for Virology and Immunobiology, University of Würzburg, Versbacher str 7, 97078 Würzburg, Germany.Abstract |
Background |
Allergic asthma is a TH2-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 TH2 but not TH1 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.
Le texte complet de cet article est disponible en PDF.Key words : Allergic asthma, costimulation, conditional CD28 knockout mice, ovalbumin, CD28-specific mAb
Abbreviations used : AHR, BAL, CTLA-4, CTLA4Ig, HDM, MLN, OVA, Treg
Plan
| Supported by Deutsche Forschungsgemeinschaft through SFB-TR52 by DFG Ta 275/4-1 and Ta 275/5-1 (to C.T.) and SFB-TR43 TP 11 (to F.L.) and the National Research Foundation (South Africa), the Medical Research Council (South Africa), and the International Center for Genetic Engineering and Biotechnology. |
|
| Disclosure of potential conflict of interest: T. Gogishvili has been supported by one or more grants from the German Research Foundation (DFG). F. Lühder has been supported by one or more grants from the State of Bavaria, Germany. C. Taube has consultancy arrangements with Novartis and Almirall and has received one or more payments for lecturing from or is on the speakers’ bureau for Business Intelligence, Novartis, Almirall, AstraZeneca, and GlaxoSmithKline. T. Hünig has been supported by one or more grants from the DFG; has consultancy arrangements with TheraMAB LLC; has received one or more grants from or has one or more grants pending with the DFG; has one or more patents (planned, pending, or issued) with the University of Würzburg; has received royalties from various companies; has received one or more payments for the development of educational presentations for Publicis Life Brands, Germany; and owns stock/stock options in TheraMAB LLC. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 130 - N° 6
P. 1394 - décembre 2012 Retour au numéro
Article précédent
- Enhanced production of CCL18 by tolerogenic dendritic cells is associated with inhibition of allergic airway reactivity
- Iris Bellinghausen, Sebastian Reuter, Helen Martin, Joachim Maxeiner, Uli Luxemburger, Özlem Türeci, Stephan Grabbe, Christian Taube, Joachim Saloga
- Phenotypic characterization of lung macrophages in asthmatic patients: Overexpression of CCL17
- Karl J. Staples, Timothy S.C. Hinks, Jon A. Ward, Victoria Gunn, Caroline Smith, Ratko Djukanović
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?