Premium
CD28/CTLA4 double deficient mice demonstrate crucial role for B7 co‐stimulation in the induction of allergic lower airways disease
Author(s) -
Deurloo D. T.,
Van Berkel M. A. T.,
Van Esch B. C. A. M.,
Hofhuis F.,
Nijkamp F. P.,
Oosterwegel M. A.,
Van Oosterhout A. J. M.
Publication year - 2003
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.2003.01757.x
Subject(s) - ovalbumin , immunology , cd28 , sensitization , stimulation , eosinophil , immunoglobulin e , cytokine , receptor , asthma , biology , t cell , medicine , immune system , endocrinology , antibody
Summary 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.