Topical CTLA4-lg suppresses ongoing mucosal immune response in presensitized murine model of allergic rhinitis

Allergic rhinitis is thought to be mediated by CD4+ T cells producing Th2-a ssociated cytokines. Optimal Ag-specific T-cell activation requires the eng agement of T-cell receptor with antigen (Ag) in the context of MHC, and the engagement of appropriate costimulatory molecules. One of the most well-ch aracterized costimulatory pathways is the interaction of B7/CD28-CTLA4 mole cules. Recent studies have suggested that the costimulatory pathway may inf luence 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 hyperr esponsiveness to histamine, nasal eosinophilia, serum levels of OVA-specifi c IgE and Th2-associated cytokines following repeated topical Ag challenges . Topical administration of CTLA4-Ig during nasal challenges inhibited Ag-i nduced nasal symptoms and histamine hyperresponsiveness. We also found a si gnificant reduction in nasal lavage eosinophilia and serum levels of OVA-sp ecific IgE, Furthermore, CTLA4-Ig treatment significantly decreased interle ukin (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 costi mulatory pathway mediates the development of ongoing Th2 immune responses a nd plays a major role in regulating allergic disease, such as allergic rhin itis.