1. CD28/CTLA4 double deficient mice demonstrate crucial role for B7 co-stimulation in the induction of allergic lower airways disease
- Author
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Deurloo, DT, van Berkel, MAT, van Esch, BCAM, Hofhuis, F, Nijkamp, FP, Oosterwegel, MA, van Oosterhout, AJM, and University of Groningen
- Subjects
airway hyper-responsiveness ,CARDIAC ALLOGRAFTS ,co-stimulation ,chemical and pharmacologic phenomena ,MURINE MODEL ,CD28 COSTIMULATION ,ALLOGRAFT SURVIVAL ,respiratory system ,asthma ,allergy ,PULMONARY EOSINOPHILIA ,CD28-DEFICIENT MICE ,T-CELL COSTIMULATION ,HYPERRESPONSIVENESS ,immunoglobulin E, T lymphocytes ,MOLECULE ICOS ,eosinophilia - Abstract
Background The existence of a third B7-1/B7-2 receptor was postulated in a recent study using a novel mouse strain lacking both CD28 and CTLA4 (CD28/CTLA4(-/-)). Objective In the present study, it was investigated if T cell co-stimulation via the putative B7-1/B7-2 receptor plays a role in the induction of Th2-mediated asthma manifestations in mice. Methods BALB/c wild-type, CD28/CTLA4(-/-) and B7-1/B7-2(-/-) mice were sensitized and aerosol challenged with ovalbumin (OVA). Results At 24 h after the last aerosol, wild-type mice showed airway hyper-responsiveness in vivo and up-regulated levels of serum OVA-specific IgE compared with the situation shortly before OVA challenge. In addition, eosinophil numbers and IL-5 levels in the broncho-alveolar lavage fluid and Th2 cytokine production by lung cells upon OVA re-stimulation in vitro were observed. In agreement with an earlier study, we failed to induce any of the asthma manifestations in B7-1/B7-2(-/-) mice. Importantly, also CD28/CTLA4(-/-) mice showed no asthma manifestations upon OVA sensitization and challenge. Conclusion These data clearly demonstrate that T cell co-stimulation via the putative B7-1/B7-2 receptor appears to have no role in the induction of Th2-mediated asthma manifestations in this murine model and, conversely, that CD28 signalling is crucial.
- Published
- 2003