RESEARCH ARTICLE Essential Contribution of CD4+ T Cells to Antigen-Induced Nasal Hyperresponsiveness in Experimental Allergic Rhinitis

Nasal hyperresponsiveness (NHR) is a characteristic feature of allergic rhinitis (AR); how-ever, the pathogenesis of NHR is not fully understood. In this study, during the establish-ment of an experimental AR model using ovalbumin-immunized and-challenged mice, augmentation of the sneezing reaction in response to nonspecific proteins as well as a chemical stimulant was detected. Whether NHR is independent of mast cells and eosino-phils was determined by using mast cell- and eosinophil-deficient mice. NHR was sup-pressed by treatment with anti-CD4 antibody, suggesting the pivotal contribution of CD4+ T cells. Furthermore, antigen challenge to mice to which in vitro-differentiated Th1, Th2, and Th17 cells but not naïve CD4+ T cells had been adoptively transferred led to the develop-ment of equivalent NHR. Since antigen-specific IgE and IgG were not produced in these mice and since antigen-specific IgE-transgenic mice did not develop NHR even upon anti-gen challenge, humoral immunity would be dispensable for NHR. CD4+ T cells play a crucial role in the pathogenesis of AR via induction of NHR, independent of IgE-, mast cell-, and eosinophil-mediated responses