TY - JOUR
T1 - CD23 exhibits negative regulatory effects on allergic sensitization and airway hyperresponsiveness
AU - Haczku, Angela
AU - Takeda, Katsuyuki
AU - Hamelmann, Eckard
AU - Loader, Joan
AU - Joetham, Anthony
AU - Redai, Imre
AU - Irvin, Charles G.
AU - Lee, James J.
AU - Kikutani, Hitoshi
AU - Conrad, Daniel
AU - Gelfand, Erwin W.
PY - 2000
Y1 - 2000
N2 - The effects of an anti-CD23 monoclonal antibody (B3B4) in CD23-deficient and CD23-overexpressing mice were compared in a murine model of allergic sensitization. After sensitization and challenge with OA, mice developed increased serum levels of OA-specific IgE and IgG1 with airway eosinophilia and AHR when compared with nonsensitized animals. Anti-CD23 treatment was studied under two protocols: 10-d OA aerosol exposure and intraperitoneal sensitization followed by aerosol challenge. In both protocols anti-CD23 significantly reduced IgE and IgG1 levels, abolished eosinophilia, and normalized AHR in BALB/c and wild-type CD23(+/+) mice but not in CD23(-/-) mice. These changes were associated with increases in IFN-γ and decreases in IL-4 production, suggesting that CD23 binding may affect not only IgE production but also the Th1/Th2 imbalance during the development of allergic AHR. Absence of CD23 in gene-deficient mice significantly enhanced OA- specific IgE and IgG1 levels, airway eosinophilia, and AHR when compared with CD23(+/+) wild-type littermates after sensitization and airway challenge. Sensitized and challenged CD23 transgenic mice also developed eosinophilic airway inflammation and methacholine hyperresponsiveness. However, the extent of AHR, BAL, and tissue eosinophilia in these animals showed a significant negative correlation with levels of CD23 expression on splenic T and B cells, demonstrating a limiting role of CD23 in the development of allergic AHR.
AB - The effects of an anti-CD23 monoclonal antibody (B3B4) in CD23-deficient and CD23-overexpressing mice were compared in a murine model of allergic sensitization. After sensitization and challenge with OA, mice developed increased serum levels of OA-specific IgE and IgG1 with airway eosinophilia and AHR when compared with nonsensitized animals. Anti-CD23 treatment was studied under two protocols: 10-d OA aerosol exposure and intraperitoneal sensitization followed by aerosol challenge. In both protocols anti-CD23 significantly reduced IgE and IgG1 levels, abolished eosinophilia, and normalized AHR in BALB/c and wild-type CD23(+/+) mice but not in CD23(-/-) mice. These changes were associated with increases in IFN-γ and decreases in IL-4 production, suggesting that CD23 binding may affect not only IgE production but also the Th1/Th2 imbalance during the development of allergic AHR. Absence of CD23 in gene-deficient mice significantly enhanced OA- specific IgE and IgG1 levels, airway eosinophilia, and AHR when compared with CD23(+/+) wild-type littermates after sensitization and airway challenge. Sensitized and challenged CD23 transgenic mice also developed eosinophilic airway inflammation and methacholine hyperresponsiveness. However, the extent of AHR, BAL, and tissue eosinophilia in these animals showed a significant negative correlation with levels of CD23 expression on splenic T and B cells, demonstrating a limiting role of CD23 in the development of allergic AHR.
UR - http://www.scopus.com/inward/record.url?scp=17144468527&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17144468527&partnerID=8YFLogxK
U2 - 10.1164/ajrccm.161.3.9905046
DO - 10.1164/ajrccm.161.3.9905046
M3 - Article
C2 - 10712348
AN - SCOPUS:17144468527
SN - 1073-449X
VL - 161
SP - 952
EP - 960
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 3 I
ER -