Velupillai P, Harn D A
Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):18-22. doi: 10.1073/pnas.91.1.18.
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.
确定导致特定CD4 + T细胞亚群（Th-1与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细胞在虫卵沉积后占主导地位。最具免疫反应性的虫卵成分是糖蛋白。此前我们在血吸虫卵和童虫上鉴定出两种有趣的寡糖。一种是乳糖-N-岩藻五糖III（LNFP-III），它含有有趣的三糖Lewisx，是P-选择素的弱配体，也是整合素淋巴细胞功能相关分子1的α链和β链上发现的一种糖，整合素淋巴细胞功能相关分子1是细胞间粘附分子1的配体。由于血吸虫卵糖蛋白与Th-2优势之间的相关性，本研究检测了LNFP-III和结构相关的寡糖是否具有淋巴细胞刺激作用和/或能否诱导已知可下调Th-1细胞的因子。我们发现LNFP-III和相关糖类确实能诱导血吸虫感染小鼠和未感染小鼠的脾脏非T细胞、B220 +、CD4 -、CD8 -细胞（B细胞）增殖。与增殖情况相反，LNFP-III是唯一能诱导脾细胞产生大量白细胞介素10和前列腺素E2的寡糖，这两种分子已知可下调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刺激并未诱导白细胞介素4的产生。因此，已鉴定出一种特异性碳水化合物配体，它能刺激B细胞增殖并产生下调Th-1 T细胞的因子。此外，我们认为相同或结构相关的配体可能在其他寄生虫病以及慢性血管疾病（如人类免疫缺陷病毒感染和一些转移性癌）中导致已知的Th-1下调，因此这种效应可能是一种普遍现象。
