Oligosaccharide-specific induction of interleukin 10 production by B220+ cells from schistosome-infected mice: a mechanism for regulation of CD4+ T-cell subsets.
Oligosaccharide-specific induction of interleukin 10 production by B220+ cells from schistosome-infected mice: a mechanism for regulation of CD4+ T-cell subsets.
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DOI：
10.1073/pnas.91.1.18
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发表时间：
1994-01
影响因子：
11.1
通讯作者：
P. Velupillai;D. Harn
中科院分区：
文献类型：
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作者：
P. Velupillai;D. Harn
确定导致特定CD 4 + T细胞亚群（Th-1 vs. Th-2）占优势的因素和/或机制是一个深入研究的领域。在小鼠血吸虫病中，Th-2型T细胞在卵沉积后成为优势。最具免疫反应性的卵成分是糖蛋白。以前，我们确定了两个有趣的寡糖发现的卵和童虫。一种是乳糖-N-岩藻五糖III（LNFP-III），含有有趣的三糖Lewisx，它是P-选择素的弱配体，也是在整联蛋白淋巴细胞功能相关分子1（细胞间粘附分子1的配体）的α和β链上发现的糖。由于间的相关性的卵蛋白和Th-2的优势，本研究探讨是否LNFP-III和结构相关的寡糖是淋巴刺激和/或能够诱导因子已知下调Th-1细胞。我们发现，LNFP-Ⅲ和相关糖确实诱导了受感染小鼠和未感染小鼠的脾脏非T细胞、B220+、CD 4-、CD 8-细胞（B细胞）的增殖。与增殖相反，LNFP-III是诱导脾细胞产生大量白细胞介素10和前列腺素E2的唯一寡糖，这两种分子已知下调Th-1细胞。此外，只有感染小鼠的脾细胞在寡糖刺激后产生细胞因子。有趣的是，LNFP-III刺激不诱导白细胞介素4的产生。因此，已经鉴定了刺激B细胞增殖并产生下调Th-1 T细胞的因子的特异性碳水化合物配体。此外，我们认为，相同的或结构相关的配体可能有助于已知的Th-1下调在其他寄生虫病和慢性血管疾病，如人类免疫缺陷病毒感染和一些转移性癌，这种效果可能，因此，是一种普遍现象。
Defining the factors and/or mechanisms that lead to the predominance of a particular CD4+ T-cell subset (Th-1 vs. Th-2) is an area of intense investigation. In murine schistosomiasis, Th-2-type T cells become predominant after deposition of eggs. The most immunoreactive egg components are glycoproteins. Previously we identified two interesting oligosaccharides found on schistosome eggs and schistosomula. One, lacto-N-fucopentaose III (LNFP-III) contains the interesting trisaccharide Lewisx, which is a weak ligand for P-selectin and is a sugar also found on the alpha and beta chains of the integrin lymphocyte function-associated molecule 1, a ligand for intercellular adhesion molecule 1. Because of the correlation between schistosome egg glycoproteins and Th-2 dominance, the present study examined whether LNFP-III and structurally related oligosaccharides were lymphostimulatory and/or able to induce factors known to down-regulate Th-1 cells. We found that LNFP-III and related sugars did induce proliferation of splenic non-T cells, B220+,CD4-,CD8- cells (B cells) of schistosome-infected and naive mice. In contrast to proliferation, LNFP-III was the only oligosaccharide that induced spleen cells to produce large amounts of interleukin 10 and prostaglandin E2, two molecules known to down-regulate Th-1 cells. Further, only spleen cells from infected mice produced cytokines after oligosaccharide stimulation. Interestingly, LNFP-III stimulation did not induce production of interleukin 4. Thus, a specific carbohydrate ligand has been identified that stimulates B cells to proliferate and produce factors that down-regulate Th-1 T cells. Further, we suggest that identical or structurally related ligands may contribute to the known Th-1 down-regulation in other parasitic diseases and in chronic blood-vascular diseases such as human immunodeficiency virus infection and a number of metastatic carcinomas and that this effect may, therefore, be a general phenomenon.