In vitro and in vivo analysis of T cell-induced bronchoconstriction
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Akio Mori, MD PhD, Satoshi Kouyama, Miyako Yamaguchi, Chiemi Kumitani, Akemi Ohtomo, Yuto Nakamura, Yasuhiro Tomita, Hamada Hamada, Yosuke Kamide, Hiroaki Hayashi, MD, Kentaro Watai, Chihiro Mitsui, MD, PhD, Kiyoshi Sekiya, Yuma Fukutomi, MD PhD, Masami Taniguchi, MD PhD, Takayuki Ohtomo, Osamu Kaminuma
RATIONALE: 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-2d. 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. Bronchoalveolar lavage was performed 48 hr after antigen challenge. Supernatants of stimulated Th clones were analyzed for contractile activity using collagen gels embedded with murine primary bronchial smooth muscle cells. Effects of antagonists against various mediators 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 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: T cell activation caused airflow limitation in addition to eosinophilic inflammation, AHR, and mucous hyperplasia. T cell-derived bronchoconstriction seems a good target for treatment-resistant asthma.