CD23 exhibits negative regulatory effects on allergic sensitization and airway hyperresponsiveness

The effects of an anti-CD23 monoclonal antibody (B3B4) in CD23-deficient an d CD23-overexpressing mice were compared in a murine model of allergic sens itization. After sensitization and challenge with OA, mice developed increa sed serum levels of OA-specific IgE and IgG(1) with airway eosinophilia and AHR when compared with nonsensitized animals, Anti-CD23 treatment was stud ied under two protocols: 10-d OA aerosol exposure and intraperitoneal sensi tization followed by aerosol challenge. In both protocols anti-CD23 signifi cantly reduced IgE and IgG(1) levels, abolished eosinophilia, and normalize d AHR in BALB/c and wild-type CD23(+/+) mice but not in CD23(-/-) mice, The se changes were associated with increases in IFN-gamma and decreases in IL- 4 production, suggesting that CD23 binding may affect not only IgE producti on but also the Th1/Th2 imbalance during the development of allergic AHR. A bsence of CD23 in gene-deficient mice significantly enhanced OA-specific Ig E and IgG(1) levels, airway eosinophilia, and AHR when compared with CD23(/+) wild-type littermates after sensitization and airway challenge. Sensiti zed and challenged CD23 transgenic mice also developed eosinophilic airway inflammation and methacholine hyperresponsiveness, However, the extent of A HR, BAL, and tissue eosinophilia in these animals showed a significant nega tive correlation with levels of CD23 expression on splenic T and B cells, d emonstrating a limiting role of CD23 in the development of allergic AHR.