Rationale: To investigate a role of helper T (Th) cells in asthma, T cell-transfer model was analyzed for late phase asthmatic response. Culture supernatants of activated T cells were analyzed for constriction of cultured bronchial smooth muscle cells.

Methods: Ovalbumin (OVA) specific Th clones were derived from splenocytes of DO11.10 transgenic mice expressing T cell receptor specific for OVA/H-2^d. Th clones were adoptively transferred into unprimed mice. Upon antigen challenge, 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. Gel filtration and ion exchange chromatography were applied to further characterize the contractile activity. Neutralizing antibodies against several candidate molecules were tested in vitro.

Results: When unprimed mice were transferred with several Th clones includind T6-2, Penh values were significantly increased 6 hr after OVA challenge. In contrast, mice transferred with other Th clones 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. Distribution of molecular mass was delineated. Several recombinant molecules indicated in vitro activity.

Conclusions: T cell activation caused airflow limitation besides eosinophilic inflammation and AHR. T cell-induced bronchoconstriction seems a good therapeutic target.