Restoration of T-box–containing protein expressed in T cells protects against allergen-induced asthma.

Background: A T_H1-specific transcription factor, T-box–containing protein expressed in T cells (T-bet), controls the production of both T_H1 and T_H2 cytokines in T_H cell differentiation by means of distinct mechanisms. T-bet–deficient mice overproduce T_H2 cytokines and have spontaneous airway inflammation. Objectives: We tested whether T-bet overexpression could protect against the development or progression of asthma. Methods: We generated a T cell–specific and inducible line of T-bet–transgenic mice on a T-bet–deficient genetic background and used it to study the function of T-bet in an ovalbumin (OVA)–induced asthma model. Results: Induction of T-bet in a T cell–specific manner in an OVA model of asthma concomitant with OVA injection prevented airway hyperresponsiveness, eosinophilic and lymphocytic inflammation, and IL-5 and IL-13 production in bronchoalveolar lavage fluid and also reduced serum IgE and T_H2 cytokine production by peripheral T cells. Even when T-bet expression was induced during later stages of asthma progression, T-bet overexpression still attenuated airway hyperresponsiveness and goblet cell hyperplasia, as well as T_H2 cytokine production. Conclusions: Our results suggest that T-bet expression in T cells can prevent the initiation of airway inflammation and progression of chronic inflammation and might be extrapolated to human asthma. [Copyright &y& Elsevier]