T CELL-INDUCED BRONCHOCONSTRICTION IN MICE

Abstract

Introduction To investigate a role of helper T (Th) cells in asthma, T cell-transfer model was analyzed for late phase asthmatic responses. Methods Ovalbumin (OVA) specific Th clones were derived from splenocytes of DO11.10 transgenic mice expressing T cell receptor specific for OVA/H-2d. Th clones were adoptively transferred into unprimed mice. After intranasal or inhalation challenge with OVA, airway resistance was continuously monitored by either unrestrained whole body plethysmography (BUXCO) or resistance/compliance analyzer under anesthetized condition. Supernatants of stimulated Th clones were analyzed for contractile activity using collagen gels embedded with murine primary bronchial smooth muscle cells. Effects of H1R and LTR1 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 OVA challenge. 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. The airflow limitation was also efficiently induced by the challenge with T cell epitope peptide, OVA323-339. Contractile activity was detected in the supernatants of T6-2 stimulated with immobilized anti-CD3. T cell-induced contraction was not affected by H1R or LTR1 antagonist. Conclusions 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.