Early IL-4 production driving Th2 differentiation in a human in vivo allergic model is mast cell derived.
Early IL-4 production driving Th2 differentiation in a human in vivo allergic model is mast cell derived.
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DOI：
10.1006/clim.1998.4628
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发表时间：
1999
影响因子：
8.6
通讯作者：
Margaret C. Wang;Andrew J. Saxon;David Diaz-Sanchez
中科院分区：
文献类型：
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作者：
Margaret C. Wang;Andrew J. Saxon;David Diaz-Sanchez
IL-4对IgE的形成和Th2效应细胞的发育至关重要，这两者都是过敏反应的关键特征。我们通过使用先前建立的人类变应性鼻炎体内模型，研究了过敏反应形成早期IL-4的产生，其中过敏受试者内部受到过敏原和颗粒污染物柴油排气颗粒（DEP）的挑战。该模型的特点是这些受试者的鼻灌洗液中IgE产生增强，并偏离th2型细胞因子谱。在该模型中，攻毒后4 h可首次检测到IL-4蛋白和IL-4阳性细胞，并在18 h后观察到最大产量。对攻毒后4 h恢复的鼻腔细胞进行双色流式细胞术检测细胞内IL-4和表面标志物。此时，CD117(+) （c-kit+）细胞占IL-4（+）细胞的65 - 100%，而IL-4（+）细胞的0-12%为CD3阳性。4 h未检测到IL-4(+) CD19/CD20（+）或IL-4(+) CD56（+）细胞。随着过敏反应的进展，IL-4的主要来源发生了变化。在攻毒18 h后IL-4产生的高峰期，CD3（+）占细胞内IL-4染色的大部分（73% ~ 100%）。因此，我们发现鼻腔粘膜中肥大细胞/嗜碱性细胞谱系的细胞在IL-4的初始产生中起着初始作用，IL-4通过扩大局部微附近产生TH2细胞因子的细胞库来构建随后的免疫反应。
IL-4 is central to the formation of IgE and the development of Th2 effector cells, both key features of an allergic response. We have examined IL-4 production early in the formation of an allergic response by using a previously established human in vivo model of allergic rhinitis where allergic subjects are challenged internasally with allergen and the particulate pollutant diesel exhaust particles (DEP). This model is characterized by enhanced IgE production and deviation to a Th2-type cytokine profile in nasal lavage fluid from these subjects. In this model, IL-4 protein and IL-4-positive cells could first be detected 4 h after challenge and maximal production was observed after 18 h. Two-color flow cytometric analysis for the detection of intracellular IL-4 and surface markers was performed on nasal cells recovered 4 h after challenge. At this time, CD117(+) (c-kit+) cells constituted between 65 and 100% of the IL-4(+) cells, while 0-12% of the IL-4(+) cells were CD3 positive. No IL-4(+) CD19/CD20(+) or IL-4(+) CD56(+) cells were detected at 4 h. As the allergic response progressed the primary source of IL-4 changed. At the peak of IL-4 production, 18 h after challenge, CD3(+) comprised the majority of cells staining for intracellular IL-4 (73 to 100%). Thus we show an initial role for cells of the mast cell/basophil lineage residing in the nasal mucosa in the initial production of IL-4, which frames the subsequent immune response by expanding the repertoire of TH2 cytokine-producing cells in the local microvicinity.