Eosinophils promote allergic disease of the lung by regulating CD4+ Th2 lymphocyte function
Eosinophils promote allergic disease of the lung by regulating CD4+ Th2 lymphocyte function
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DOI：
10.4049/jimmunol.167.6.3146
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发表时间：
2001-09-15
影响因子：
4.4
通讯作者：
Foster, PS
中科院分区：
文献类型：
--
作者：
MacKenzie, JR;Mattes, J;Foster, PS
嗜酸性粒细胞主要被认为是过敏反应和寄生虫消除的终末效应器。然而，有限的研究表明这种白细胞在这些炎症反应期间具有更离散的免疫调节作用。在这项研究中，我们强调了嗜酸性粒细胞作为 APC 的潜力，从而通过影响 Th2 细胞功能来调节过敏反应。为了响应Ag对过敏性肺部的刺激，嗜酸性粒细胞迅速运输到Ag沉积部位（气道腔）和呈现部位（肺相关淋巴结和富含T细胞的副皮质区）。来自过敏性肺的嗜酸性粒细胞表达 II 类 MHC 肽、T 细胞共刺激分子（CD80 和 CD86），并快速内化和处理从气道腔内取样的 Ag。负载Ag的嗜酸性粒细胞在与体外极化的Th2细胞共培养中促进IL-4、IL-5和IL-13的产生，并以剂量依赖性方式诱导从过敏小鼠分离的Ag特异性CD4+T细胞产生IL-5。此外，当将负载Ag的嗜酸性粒细胞转移至初始小鼠体内时，其会引发Th2细胞驱动的肺部过敏性疾病。因此，嗜酸性粒细胞不仅有可能激活 Th2 细胞释放疾病调节细胞因子，而且有可能帮助启动免疫系统进行过敏反应。这项研究强调了嗜酸性粒细胞不仅可以充当终末效应细胞，还可以通过放大 Th2 细胞反应来主动调节过敏性炎症。
Eosinophils are primarily thought of as terminal effectors of allergic responses and of parasite elimination. However, limited studies suggest a more discrete immunomodulatory role for this leukocyte during these inflammatory responses. In this investigation, we highlight the potential of eosinophils to act as APCs and thus modulators of allergic responses by influencing Th2 cell function. In response to Ag provocation of the allergic lung, eosinophils rapidly trafficked to sites of Ag deposition (airways lumen) and presentation (lung-associated lymph nodes and T cell-rich paracortical zones). Eosinophils from the allergic lung expressed class II MHC peptides, T cell costimulatory molecules (CD80 and CD86), and rapidly internalized and processed Ag that was sampled from within the airway lumen. Ag-loaded eosinophils promoted the production of IL-4, IL-5, and IL-13 in cocultures with in vitro-polarized Th2 cells and induced IL-5 production in a dose-dependent manner from Ag-specific CD4(+) T cells isolated from allergic mice. In addition, Ag-loaded eosinophils primed for Th2 cell-driven allergic disease of the lung when transferred to naive mice. Thus, eosinophils have the potential to not only activate Th2 cells to release disease-modulating cytokines but also to assist in priming the immune system for allergic responses. This investigation highlights the potential of eosinophils to not only act as terminal effector cells but also to actively modulate allergic inflammation by amplifying Th2 cell responses.