Allergic rhinitis is thought to be mediated by CD4+ T cells producing Th2-associated
cytokines. Optimal Ag-specific T-cell activation requires the engagement of
T-cell receptor with
antigen (Ag) in the context of MHC, and the engagement of appropriate costimulatory molecules. One of the most well-characterized costimulatory pathways is the interaction of B7/CD28-CTLA4 molecules. Recent studies have suggested that the costimulatory pathway may influence the development of Th2 immune responses. The objective of this study was the examination of the role of B7/CD28-CTLA4 costimulatory pathway in the pathogenesis of
ovalbumin (OVA)-induced immune response in presensitized murine model of
allergic rhinitis. Systemically presensitized BALB/c mice significantly developed Ag-induced early phase nasal symptoms, nasal hyperresponsiveness to
histamine, nasal
eosinophilia, serum levels of OVA- specific
IgE and Th2-associated
cytokines following repeated topical Ag challenges.
Topical administration of
CTLA4-Ig during nasal challenges inhibited Ag-induced nasal symptoms and
histamine hyperresponsiveness. We also found a significant reduction in nasal lavage
eosinophilia and serum levels of OVA-specific
IgE. Furthermore,
CTLA4-Ig treatment significantly decreased
interleukin (IL)-4 content in nasal tissue, while there was no significant change in
IL-5 or IFN-gamma levels. These results suggest that B7/CD28-CTLA4 costimulatory pathway mediates the development of ongoing Th2 immune responses and plays a major role in regulating allergic disease, such as
allergic rhinitis.