Inhibition of T1/ST2 during respiratory syncytial virus infection prevents T helper cell type 2 (Th2)- but not Th1-driven immunopathology.
Inhibition of T1/ST2 during respiratory syncytial virus infection prevents T helper cell type 2 (Th2)- but not Th1-driven immunopathology.
复制标题
呼吸道合胞病毒感染期间抑制 T1/ST2 可预防 2 型辅助 T 细胞 (Th2)，但不能预防 Th1 驱动的免疫病理学。
DOI：
10.1084/jem.193.7.785
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发表时间：
2001-04-02
影响因子：
15.3
通讯作者：
Hussell, T
中科院分区：
文献类型：
--
作者：
Walzl, G;Matthews, S;Kendall, S;Gutierrez-Ramos, J C;Coyle, A J;Openshaw, P J;Hussell, T
分泌白细胞介素（IL）-4和IL-5的T细胞（辅助性T细胞2型[Th 2]细胞）在多种疾病中发挥有害作用，但调节其活性的具体方法仍然难以捉摸。T1/ST 2是IL-1受体家族的表面配体，在Th 2-而不是在产生干扰素（IFN）-γ的Th 1细胞上表达。BALB/c小鼠先前暴露于呼吸道合胞病毒（RSV）的附着（G）或融合（F）蛋白会增加鼻内RSV攻毒期间的疾病严重程度，这分别是由于Th 2驱动的肺嗜酸性粒细胞增多和Th 1驱动的肺浸润旺盛。我们使用这些病毒性疾病的极性模型来研究T1/ST 2细胞向肺的募集，并测试抗T1/ST 2治疗的体内效果。T1/ST 2存在于嗜酸性粒细胞性肺病小鼠的CD 4+细胞亚群上。单克隆抗T1/ST 2治疗减少了Th 2（而不是Th 1）免疫病理学小鼠的肺部炎症和疾病的严重程度。这些结果表明，T1/ST 2的抑制对病毒诱导的Th 2应答具有特异性作用，并表明靶向该受体的治疗可能在治疗Th 2驱动的疾病中具有价值。
T cells secreting interleukin (IL)-4 and IL-5 (T helper cell type 2 [Th2] cells) play a detrimental role in a variety of diseases, but specific methods of regulating their activity remain elusive. T1/ST2 is a surface ligand of the IL-1 receptor family, expressed on Th2- but not on interferon (IFN)-γ–producing Th1 cells. Prior exposure of BALB/c mice to the attachment (G) or fusion (F) protein of respiratory syncytial virus (RSV) increases illness severity during intranasal RSV challenge, due to Th2-driven lung eosinophilia and exuberant Th1-driven pulmonary infiltration, respectively. We used these polar models of viral illness to study the recruitment of T1/ST2 cells to the lung and to test the effects of anti-T1/ST2 treatment in vivo. T1/ST2 was present on a subset of CD4+ cells from mice with eosinophilic lung disease. Monoclonal anti-T1/ST2 treatment reduced lung inflammation and the severity of illness in mice with Th2 (but not Th1) immunopathology. These results show that inhibition of T1/ST2 has a specific effect on virally induced Th2 responses and suggests that therapy targeted at this receptor might be of value in treating Th2-driven illness.