Effects of LTRA on T cell-induced bronchoconstriction in the mice

Aims: To investigate a role of helper T (Th) cells in asthma, T cell-transfer model was analyzed for late phase asthmatic response. Methods: Ovalbumin (OVA) specific Th clones were derived from either the regional lymphnodes of Balb/c mice immunized with OVA/CFA or splenocytes of DO11.10 transgenic mice expressing T cell receptor specific for OVA/H-2 d . Th clones were adoptively transferred into unprimed mice. After antigen challenge, airway resistance was continuously monitored by either unrestrained whole body plethysmography(BUXCO) or resistance/compliance analyzer under anesthetized condition. Bronchoalveolar lavage analysis was performed 48 hr after OVA challenge. Supernatants of stimulated Th clones were analyzed for contractile activity using collagen gels embedded with murine primary bronchial smooth muscle cells. Effects of H 1 R and LTR 1 antagonist were analyzed both in vitro and in vivo . Results: When unprimed mice were transferred with Th clones, T5-1, T6-2, T6-4, and T6-7, Penh values were significantly increased 6 hr after challenge with OVA or T cell epitope peptide, OVA 323-339 . In contrast, mice transferred with other Th clones, BF7, T6-1, or T6-10 did not show any change. Airflow limitation was confirmed by a direct measurement of airway resistance under anesthetized, restrained, and intubated conditions. Contractile activity was detected in the supernatants of T6-2 stimulated with immobilized anti-CD3. T cell-induced contraction was not affected by H 1 R or LTR 1 antagonist. Conclusion: Activation of Th cells resulted in an airflow limitation besides eosinophilic inflammation, AHR, and mucous hyperplasia. T cell-derived bronchoconstrictor might be a target for treatment-resistant asthma.