CD137-mediated immunotherapy for allergic asthma
CD137-mediated immunotherapy for allergic asthma
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DOI：
10.1172/jci23792
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发表时间：
2006-04-01
影响因子：
15.9
通讯作者：
Hansen, G
中科院分区：
文献类型：
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作者：
Polte, T;Foell, J;Hansen, G
哮喘患病率持续上升。哮喘是由Th2细胞驱动的免疫反应引起的。它的最佳治疗方法仍然是一个挑战，并且尚未找到治疗哮喘的充分的免疫治疗方法。通过小鼠哮喘模型，我们发现单次注射抗cd137 （4-1BB）单抗可以在7周的观察期内防止气道高反应性、嗜酸性气道炎症、粘液分泌过多和IgE升高。最重要的是，即使是既定的疾病，也可以通过抗cd137单抗治疗完全逆转。这种保护作用与显著减少Th2细胞因子的产生和增加Th1细胞因子ifn - γ的分泌有关。当B淋巴细胞部分减少时，CD8(+) T细胞的数量增加。在使用抗CD137单抗治疗期间，ifn - γ的阻断和CD8(+) T细胞的耗竭部分减少，但不取消CD137单抗的保护作用。相反，CD137单抗介导的CD4(+) T细胞能量对于观察到的效果至关重要，因为CD137单抗处理小鼠的CD4(+) T细胞转移传递了保护作用。据我们所知，这些数据首次证明了抗CD137单抗改善过敏性哮喘的能力，并表明CD137可能是这种疾病治疗干预的靶点。
The prevalence of asthma continues to increase. Asthma is caused by a Th2 cell-driven immune response. Its optimal treatment remains a challenge, and a sufficient immunotherapeutic approach to treating asthma has yet to be found. Using a murine asthma model, we show that a single injection of an anti-CD137 (4-1BB) mAb prevents the development of airway hyperreactivity, eosinophilic airway inflammation, excessive mucus production, and elevated IgE during the observation period of 7 weeks. Most importantly, even established disease is completely reversed by anti-CD137 mAb administration. The protection is associated with markedly reduced Th2 cytokine production and increased secretion of the Th1 cytokine IFN-gamma. While B lymphocytes are partly depleted, the number of CD8(+) T cells is increased. Blockade of IFN-gamma and depletion of CD8(+) T cells during treatment with anti-CD137 mAb reduces in part but does not abrogate the protective effect of CD137 mAb. In contrast, CD137 mAb-mediated CD4(+) T cell anergy is critical for the observed effects, since transfer of CD4(+) T cells from CD137 mAb-treated mice conveyed protection. These data demonstrate, for the first time to our knowledge, the capacity of anti-CD137 mAb to ameliorate allergic asthma, and they indicate CD137 as a possible target for therapeutic intervention in this disease.