CD23 exhibits negative regulatory effects on allergic sensitization and airway hyperresponsiveness.
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 IgG(1) 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 IgG(1) 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-gamma 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 IgG(1) 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.
Haczku
A
A
Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Takeda
K
K
Hamelmann
E
E
Loader
J
J
Joetham
A
A
Redai
I
I
Irvin
C G
CG
Lee
J J
JJ
Kikutani
H
H
Conrad
D
D
Gelfand
E W
EW
D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D004804:Eosinophils / Q000502:physiology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017455:Receptors, IgE / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D007074:Immunoglobulin G; D017455:Receptors, IgE; D007073:Immunoglobulin E