Lee Jee-Boong, Jang Ji-Eun, Song Man Ki, Chang Jun
Division of Life and Pharmaceutical Sciences, and Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Republic of Korea.
PLoS One. 2009;4(4):e5190. doi: 10.1371/journal.pone.0005190. Epub 2009 Apr 10.
Cholera toxin (CT) is a potent vaccine adjuvant, which promotes mucosal immunity to protein antigen given by nasal route. It has been suggested that CT promotes T helper type 2 (Th2) response and suppresses Th1 response. We here report the induction of Th17-dominated responses in mice by intranasal delivery of CT. This dramatic Th17-driving effect of CT, which was dependent on the B subunit, was observed even in Th1 or Th2-favored conditions of respiratory virus infection. These dominating Th17 responses resulted in the significant neutrophil accumulation in the lungs of mice given CT. Both in vitro and in vivo treatment of CT induced strongly augmented IL-6 production, and Th17-driving ability of CT was completely abolished in IL-6 knockout mice, indicating a role of this cytokine in the Th17-dominated T-cell responses by CT. These data demonstrate a novel Th17-driving activity of CT, and help understand the mechanisms of CT adjuvanticity to demarcate T helper responses.
霍乱毒素（CT）是一种有效的疫苗佐剂，可促进对经鼻途径给予的蛋白质抗原的黏膜免疫。有人认为CT可促进2型辅助性T细胞（Th2）反应并抑制Th1反应。我们在此报告通过鼻内递送CT在小鼠中诱导以Th17为主导的反应。即使在呼吸道病毒感染的Th1或Th2偏向条件下，也观察到CT这种显著的Th17驱动作用，其依赖于B亚基。这些占主导地位的Th17反应导致给予CT的小鼠肺部有明显的中性粒细胞积聚。CT的体外和体内处理均强烈增强了白细胞介素-6（IL-6）的产生，并且在IL-6基因敲除小鼠中CT的Th17驱动能力完全丧失，表明该细胞因子在CT介导的以Th17为主导的T细胞反应中起作用。这些数据证明了CT的一种新的Th17驱动活性，并有助于理解CT佐剂作用以区分辅助性T细胞反应的机制。
