RT Journal Article SR Electronic T1 Blocking costimulatory signal for treating steroid-resistant asthma model JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP P2321 VO 40 IS Suppl 56 A1 Akio Mori A1 Akemi Abe A1 Satoshi Kouyama A1 Miyako Yamaguchi A1 Mika Enoki A1 Yo Iijima A1 Chihiro Mitsui A1 Chiyako Oshikata A1 Hidenori Tanimoto A1 Yuma Fukutomi A1 Kiyoshi Sekiya A1 Masami Taniguchi A1 Yuji Maeda A1 Mamoru Ohtomo A1 Maki Hasegawa A1 Kazuo Akiyama A1 Takayuki Ohtomo A1 Osamu Kaminua YR 2012 UL http://erj.ersjournals.com/content/40/Suppl_56/P2321.abstract AB Background: We have constructed steroid sensitive (SS) and resistant (SR) murine asthma models by transferring SS and SR helper T (Th) clones into unprimed mice, respectively. Effect of CTLA4-Ig was analyzed both in vitro and in vivo.Method: For in vitro experiments, ovalbumin (OVA) reactive Th clones were cultured with antigen presenting cells, OVA, and various concentrations of dexamethasone (DEX). The proliferative response of each Th clone was measured by 3H-thymidine uptake. For in vivo experiments, unprimed BALB/c mice were transferred with Th clones, challenged with OVA, and administered with DEX subcutaneously. CTLA4-Ig was administered through nasal inhalation or venous injection. The number of infiltrating cells in bronchoalveolar lavage fluid (BALF) was measured.Results: SS and SR clones were selected in terms of the in vitro effect of DEX on the proliferative responses of antigen-stimulated clones. Airway infiltration of eosinophils and lymphocytes of mice transferred with SS clones were effectively inhibited by the administration of DEX. In contrast, those of mice transferred with SR clones were not significantly inhibited by DEX. Administration of CTLA4-Ig significantly suppressed in vitro proliferation of DEX-treated SR clones, and in vivo eosinophil infiltration of SR asthma model transferred with SR clones.Conclusion: Steroid sensitivity of Th clones measured in vitro were consistent with that of adoptively transferred asthma model measured in vivo. Steroid resistant asthma models can be treated by blocking costimulatory signal mediated through CD28-CD80 and 86.