CD4(+) T helper cells engineered to produce latent TGF-beta 1 reverse allergen-induced airway hyperreactivity and inflammation

T helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the precise immunological mechanisms that inhibit Th2 cell function in vivo are not well understood Using gene therapy, we demonstrated that ovalb umin-specific (OVA-specific) Th cells engineered to express latent TGF-beta abolished airway hyperreactivity and airway inflammation induced by OVA-sp ecific Th2 effector cells in SCID and BALB/c mice. These effects correlated with increased concentrations of active TGF-beta in the bronchoalveolar la vage (BAL) fluid, demonstrating that latent TGF-beta was activated in the i nflammatory environment. In contrast, OVA-specific Th1 cells failed to inhi bit airway hyperreactivity and inflammation in this system. The inhibitory effect of TGF-beta-secreting Th cells was antigen-specific and was reversed by neutralization of TGF-beta. Our results demonstrate that T cells secret ing TGF-beta in the respiratory mucosa can indeed regulate Th2-induced airw ay hyperreactivity and inflammation and suggest that TGF-beta-producing T c ells play an important regulatory role in asthma.