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

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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

Int Arch Allergy Immunol. 1999 Jul;119(3):197-204. Unique Identifier : AIDSLINE MED/99367829
Sato J; Asakura K; Murakami M; Uede T; Kataura A; Department of Otolaryngology, Sapporo Medical University, School; of Medicine, Hokkaido University, Sapporo, Japan.

Abstract: 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.

Keywords: JOURNAL ARTICLE Animal Antigens, Differentiation/*IMMUNOLOGY Immunity, Mucosal/*IMMUNOLOGY Male Mice Mice, Inbred BALB C Rhinitis, Allergic, Perennial/*IMMUNOLOGY Th2 Cells/*IMMUNOLOGY
991130
A99B1056

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