Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, UK.
Eur J Immunol. 2011 Sep;41(9):2709-18. doi: 10.1002/eji.201141429. Epub 2011 Aug 4.
Immunization with Schistosoma mansoni soluble antigen preparations protects non-obese diabetic (NOD) mice against the development of type 1 diabetes. These preparations have long been known to induce Th2 responses in vitro and in vivo. Recently, two separate groups have reported that ω-1, a well-characterized glycoprotein in S. mansoni soluble egg antigens (SEA), which with IL-4 inducing principle of S. mansoni eggs (IPSE/α-1) is one of the two major glycoproteins secreted by live eggs, is a major SEA component responsible for this effect. We found that ω-1 induces Foxp3 as well as IL-4 expression when injected in vivo. We confirmed that ω-1 conditions DCs to drive Th2 responses and further demonstrated that ω-1 induces Foxp3(+) T cells from NOD mouse naïve T cells. In contrast, IPSE/α-1 did not drive Foxp3 responses. The in vitro development of Foxp3-expressing T cells by ω-1 was TGF-β- and retinoic acid-dependent. Our work, therefore, identifies ω-1 as an important factor for the induction of Foxp3(+) T cells by SEA in NOD mice.
用曼氏血吸虫可溶性抗原制剂进行免疫接种可保护非肥胖型糖尿病（NOD）小鼠免受 1 型糖尿病的发生。这些制剂早已被证实能在体外和体内诱导 Th2 反应。最近，两个独立的研究小组报道，ω-1，一种在曼氏血吸虫可溶性卵抗原（SEA）中得到很好表征的糖蛋白，与诱导曼氏血吸虫卵的 IL-4 原理（IPSE/α-1）一起，是由活卵分泌的两种主要糖蛋白之一，是导致这种效应的主要 SEA 成分之一。我们发现，ω-1 在体内注射时会诱导 Foxp3 和 IL-4 的表达。我们证实，ω-1 使 DC 条件化从而驱动 Th2 反应，并且进一步表明，ω-1 能从 NOD 小鼠幼稚 T 细胞诱导 Foxp3(+)T 细胞。相比之下，IPSE/α-1 不能驱动 Foxp3 反应。体外培养的 Foxp3 表达 T 细胞依赖于 TGF-β 和维甲酸。因此，我们的工作确定了 ω-1 是 SEA 在 NOD 小鼠中诱导 Foxp3(+)T 细胞的一个重要因素。
