Everts Bart, Perona-Wright Georgia, Smits Hermelijn H, Hokke Cornelis H, van der Ham Alwin J, Fitzsimmons Colin M, Doenhoff Michael J, van der Bosch Jürgen, Mohrs Katja, Haas Helmut, Mohrs Markus, Yazdanbakhsh Maria, Schramm Gabriele
Department of Parasitology, Leiden University Medical Centre, Leiden 2333 ZA, The Netherlands.
J Exp Med. 2009 Aug 3;206(8):1673-80. doi: 10.1084/jem.20082460. Epub 2009 Jul 27.
Soluble egg antigens of the parasitic helminth Schistosoma mansoni (S. mansoni egg antigen [SEA]) induce strong Th2 responses both in vitro and in vivo. However, the specific molecules that prime the development of Th2 responses have not been identified. We report that omega-1, a glycoprotein which is secreted from S. mansoni eggs and present in SEA, is capable of conditioning human monocyte-derived dendritic cells in vitro to drive T helper 2 (Th2) polarization with similar characteristics as whole SEA. Furthermore, using IL-4 dual reporter mice, we show that both natural and recombinant omega-1 alone are sufficient to generate Th2 responses in vivo, even in the absence of IL-4R signaling. Finally, omega-1-depleted SEA displays an impaired capacity for Th2 priming in vitro, but not in vivo, suggesting the existence of additional factors within SEA that can compensate for the omega-1-mediated effects. Collectively, we identify omega-1, a single component of SEA, as a potent inducer of Th2 responses.
寄生蠕虫曼氏血吸虫的可溶性虫卵抗原（曼氏血吸虫虫卵抗原[SEA]）在体外和体内均可诱导强烈的Th2反应。然而，启动Th2反应发展的特定分子尚未确定。我们报告称，ω-1是一种从曼氏血吸虫虫卵分泌并存在于SEA中的糖蛋白，它能够在体外调节人单核细胞衍生的树突状细胞，以驱动具有与完整SEA相似特征的辅助性T细胞2（Th2）极化。此外，使用IL-4双报告基因小鼠，我们发现天然和重组的ω-1单独就足以在体内产生Th2反应，即使在没有IL-4R信号传导的情况下也是如此。最后，去除ω-1的SEA在体外显示出Th2启动能力受损，但在体内未受损，这表明SEA中存在其他可以补偿ω-1介导作用的因素。总体而言，我们确定SEA的单一成分ω-1是Th2反应强力诱导剂。
