Hsu Shih-Chang, Tsai Tsung-Hsien, Kawasaki Hirokazu, Chen Chien-Ho, Plunkett Beverly, Lee Reiko T, Lee Yuan C, Huang Shau-Ku
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA.
J Allergy Clin Immunol. 2007 Jun;119(6):1522-8. doi: 10.1016/j.jaci.2007.01.034. Epub 2007 Mar 13.
Glycoproteins containing Lewis-x (Le(x)) trisaccharides are often associated with the host's adaptive T(H)2-type immunity, but the mechanisms underlying the T(H)2-biased response are at present unclear.
The modulatory effect of Le(x) or its glycoconjugates on IgE/T(H)2 responses was investigated.
The levels of serum antibodies and cytokines were analyzed by means of ELISA, RT-PCR, or both.
In C3H mice Le(x) coupled with BSA (Le(x)-BSA) elicited higher levels of specific IgE and IgG1, but not IgG2a, which were associated with increased levels of splenic T(H)2 cytokines when compared with those seen in BSA-sensitized mice. In BALB/c mice sensitized with Le(x)-BSA or Le(x) mixed with ovalbumin, significantly increased levels of specific IgE and IgG2a antibodies were found concomitant with reduced levels of serum IL-12p70. These effects were attenuated in IL-12-deficient BALB/c mice. Le(x) and an isomer, Le(y), but not other isomers, inhibited the production of LPS-induced IL-12p70, associated with a significant reduction of nuclear NF-kappaB, in bone marrow-derived dendritic cells from BALB/c mice, suggesting that Le(x)-induced suppression of IL-12p70 results in an enhanced T(H)2 response. The addition of mannan, a known ligand for dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin, abrogated the suppressive effect of Le(x) trisaccharides.
These results provide evidence for a potential role of Le(x) trisaccharides in shaping the immune responses through, at least in part, its suppressive effect on IL-12p70 production. Considering the relative ubiquity of glycoproteins with Le(x) or similar oligosaccharides, including plant-derived (or food-derived) allergens, these findings might have a broad implication.
The adjuvant activity of Le(x) trisaccharides might aid in vaccine design and might be important in determining the allergenicity of proteins containing this or other similar structures.
含有Lewis-x（Le(x)）三糖的糖蛋白通常与宿主的适应性T(H)2型免疫相关，但目前T(H)2偏向性反应的潜在机制尚不清楚。
研究Le(x)或其糖缀合物对IgE/T(H)2反应的调节作用。
通过ELISA、RT-PCR或两者分析血清抗体和细胞因子水平。
在C3H小鼠中，与牛血清白蛋白偶联的Le(x)（Le(x)-BSA）诱导产生更高水平的特异性IgE和IgG1，但不诱导IgG2a，与牛血清白蛋白致敏小鼠相比，这与脾脏T(H)2细胞因子水平升高有关。在用Le(x)-BSA或与卵清蛋白混合的Le(x)致敏的BALB/c小鼠中，发现特异性IgE和IgG2a抗体水平显著升高，同时血清IL-12p70水平降低。在IL-12缺陷的BALB/c小鼠中，这些效应减弱。Le(x)及其异构体Le(y)，而非其他异构体，抑制了BALB/c小鼠骨髓来源树突状细胞中脂多糖诱导的IL-12p70的产生，这与核NF-κB的显著减少相关，表明Le(x)诱导的IL-12p70抑制导致T(H)2反应增强。添加甘露糖（一种已知的树突状细胞特异性细胞间粘附分子3结合非整合素的配体）可消除Le(x)三糖的抑制作用。
这些结果为Le(x)三糖在至少部分通过对IL-12p70产生的抑制作用来塑造免疫反应中的潜在作用提供了证据。考虑到含有Le(x)或类似寡糖的糖蛋白相对普遍存在，包括植物来源（或食物来源）的过敏原，这些发现可能具有广泛的意义。
Le(x)三糖的佐剂活性可能有助于疫苗设计，并且在确定含有这种或其他类似结构的蛋白质的致敏性方面可能很重要。
