Presentation: Development and treatment of steroid resistant asthma model by adoptive transfer of murine helper t cell clones (WAO International Scientific Conference 2014)

Sunday, 7 December 2014: 18:10 - 18:30

Exhibition Hall-Poster Area (Sul America)

Akio Mori, MD, PhD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Satoshi Kouyama, MSc , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Miyako Yamaguchi , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Yo Iijima , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Akemi Ohtomo, PhD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Takayuki Ohtomo, PhD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Jun Itoh, MD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Hiroaki Hayashi, MD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Kentaro Watarai, MD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Chihiro Mitsui, MD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Chiyako Oshikata, MD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Yuma Fukutomi, MD, PhD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Kiyoshi Sekiya, MD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Takahiro Tsuburai, MD, PhD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Yuji Maeda, MD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Mamoru Ohtomo, MD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Masami Taniguchi, MD, PhD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Kazuo Akiyama, MD , Clinical Research Center, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan

Osamu Kaminuma, PhD , Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

Background: To investigate the role of helper T (Th) cells in steroid resistant (SR) asthma, steroid sensitive (SS) and resistant (SR) Th clones were selected in vitro, and then adoptively transferred into unprimed mice. Effect of CTLA4-Ig was analyzed both in vitro and in vivo.

Methods: For in vitro evaluation of steroid sensitivity, ovalbumin (OVA) reactive Th clones were cultured with antigen presenting cells and OVA in the presence of various concentrations of dexamethasone (DEX). Proliferative responses of Th clones were measured by ³H-thymidine incorporation. For in vivo evaluation, unprimed BALB/c mice were transferred with Th clones, challenged with OVA, and administered with DEX subcutaneously. Bronchoalveolar lavage fluid (BALF) was obtained 48 hr after challenge, and the number of infiltrating cells was differentially counted. CTLA4-Ig was administered either intravenously or intranasally.

Results: SS and SR clones were selected based on the suppressive effect of DEX on the proliferative responses of antigen-stimulated Th 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. Administration of CTLA4-Ig significantly suppressed the proliferation of DEX-treated SR clones in vitro, and the eosinophil infiltration of mice transferred with SR clones in vivo.

Conclusions: Steroid sensitivity of Th clones assessed in vitro was consistent with that of adoptively transferred asthma model assessed in vivo. Costimulatory signal mediated through CD28 is crucial for the induction of steroid resistance both in vitro and in vivo.

1012 Development and treatment of steroid resistant asthma model by adoptive transfer of murine helper t cell clones