Murasugi Takako, Nakagami Yasuhiro, Yoshitomi Tomomi, Hirahara Kazuki, Yamashita Makoto, Taniguchi Yoshifumi, Sakaguchi Masahiro, Ito Kazuhiro
Biological Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Eur J Pharmacol. 2005 Mar 7;510(1-2):143-8. doi: 10.1016/j.ejphar.2005.01.003.
Although the concept of a T cell epitope in specific immunoprophylaxis was proposed more than a decade ago, it had not been well demonstrated since then that a T cell epitope inhibits symptoms and reactions of allergic disease in animal models. In this study, we have established a system to evaluate symptoms and reactions of allergic rhinitis in mice, and investigated whether oral administration of a T cell epitope relieves sensitized mice of allergic rhinitis. P2-246-259 (RAEVSYVHVNGAKF) is a BALB/c mouse T-cell epitope of Cry j 2, which is a major Japanese cedar (Cryptomeria japonica) pollen allergen. Mice were administered orally with 200 microg/animal of P2-246-259 four times within 2 weeks before sensitization, and sensitized intranasally with Cry j 2 twice. Of the cardinal symptoms of allergic rhinitis, we assessed sneezing and airway obstruction, but could not estimate rhinorrhea or pruritus. Sneezing frequency was significantly increased by challenge with Cry j 2. Concerning allergic reactions, vascular permeability of the nasal mucosa in the early phase and hyperreactivity to histamine in the late phase were also exacerbated by the challenge. These symptoms and reactions of allergic rhinitis were significantly inhibited by oral administration of P2-246-259. These results indicate utility of mice as models for allergic rhinitis; furthermore, the effects of P2-246-259 on allergic rhinitis imply that oral administration of a T cell epitope is a promising approach for specific immunoprophylaxis.
尽管早在十多年前就提出了T细胞表位在特异性免疫预防中的概念,但从那时起,尚未充分证明T细胞表位能在动物模型中抑制变应性疾病的症状和反应。在本研究中,我们建立了一个评估小鼠变应性鼻炎症状和反应的系统,并研究口服T细胞表位是否能使致敏小鼠缓解变应性鼻炎。P2-246-259(RAEVSYVHVNGAKF)是日本柳杉花粉主要变应原Cry j 2 的BALB/c小鼠T细胞表位。在致敏前2周内给小鼠口服200μg/只P2-246-259,共4次,然后经鼻内给予Cry j 2 致敏2次。对于变应性鼻炎的主要症状,我们评估了喷嚏和气道阻塞,但无法评估鼻漏或瘙痒症状。用Cry j 2 激发后,喷嚏频率显著增加。关于变应性反应,激发也会加剧早期鼻黏膜血管通透性和晚期对组胺的高反应性。口服P2-246-259可显著抑制这些变应性鼻炎症状和反应。这些结果表明小鼠可作为变应性鼻炎模型;此外,P2-246-259对变应性鼻炎的作用表明口服T细胞表位是一种很有前景的特异性免疫预防方法。