Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet

Human asthma is associated with airway infiltration by T helper 2 (T(H)2) lymphocytes. We observed reduced expression of the T(H)1 transcription factor, T-bet, in T cells from airways of patients with asthma compared with that in T cells from airways of nonasthmatic patients, suggesting that loss of T-bet might be associated with asthma. Mice with a targeted deletion of the T-bet gene and severe combined immunodeficient mice receiving CD4(+) cells from T-bet knockout mice spontaneously demonstrated multiple physiological and inflammatory features characteristic of asthma, Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma.