Allergic experimental asthma can be ameliorated by allergen specific immunotherapy in the absence of T-bet. (55.6)

Abstract

Abstract Clinical studies have demonstrated that repeated subcutaneous (s.c.) administrations of allergen are effective in the treatment of allergic diseases. It has been suggested, that the success of this treatment, also known as allergen specific immunotherapy (IT), relates to a shift of the T helper 2 (Th2) to T helper 1 (Th1) cells, a blockade of specific antibodies and/or the induction of regulatory T cells (Treg). The T box transcription factor (T-bet) is crucial for the Th1 development and previous studies demonstrated that T-bet deficient mice (T-bet KO) develop a severe asthmatic phenotype. Thus we address the question of whether T-bet is necessary for the effectiveness of IT. T-bet KO mice were analyzed in a murine model of allergic airway disease and IT. OVA-sensitized T-bet KO or BALB/c mice were treated with 3 s.c. injections of OVA (1000µg/injection) prior to airway challenge. This treatment was effective in suppressing the allergen-induced asthma manifestations such as airway hyperresponsiveness (AHR), serum IgE, lung eosinophilia and airway inflammation in sensitized and challenged wildtype mice. Consistently Th2 cytokines were reduced in the lung of IT treated mice. IT treated T-bet KO mice showed an alleviated airway disease following IT to a comparable degree as that observed in the wildtype mice. In summary, the present study shows that IT is not dependent on T-bet and that this treatment effectively suppresses the development of AHR and airway inflammation.