Lymph node trafficking and antigen presentation by endobronchial eosinophils
Lymph node trafficking and antigen presentation by endobronchial eosinophils
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DOI：
10.1172/jci8945
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发表时间：
2000-04-01
影响因子：
15.9
通讯作者：
Weller, PF
中科院分区：
文献类型：
--
作者：
Shi, HZ;Humbles, A;Weller, PF
由于在过敏性疾病中招募到气道中的嗜酸性粒细胞暴露于吸入性过敏原，因此我们评估了支气管内腔内的嗜酸性粒细胞是否可以在体内发挥吸入抗原的抗原呈递细胞的作用。我们从致敏小鼠气溶胶抗原攻击后的气道中或从IL-5转基因小鼠的腹腔中回收了嗜酸性粒细胞，并对这些细胞进行离体荧光标记。这些标记的细胞被注入正常小鼠气管内，迁移到引流气管旁淋巴结并定位于富含 T 细胞的副皮质区域。气道嗜酸性粒细胞向淋巴结的归巢不受嗜酸性粒细胞趋化因子的控制，因为CCR3(-/-)和CCR3(+/+)嗜酸性粒细胞的迁移相同。致敏小鼠吸入抗原攻击后恢复的气道嗜酸性粒细胞表达 MHC II 类和共刺激 CD80 和 CD86 蛋白，并在体外作为 CD80 和 CD86 依赖性、抗原特异性、抗原呈递细胞发挥作用。此外，当注入抗原致敏受体小鼠气道时，吸入抗原激发刺激气管旁淋巴结内抗原特异性CD4(+) T细胞增殖，气道嗜酸性粒细胞恢复。因此，气道腔内的嗜酸性粒细胞可以处理吸入的抗原，运输至区域淋巴结，并在体内作为抗原呈递细胞发挥作用，刺激CD4(+) T细胞的反应。
Because eosinophils recruited into the airways in allergic diseases are exposed to inhaled allergens, we evaluated whether eosinophils within the endobronchial lumen can function in vivo as antigen-presenting cells for inhaled antigens. We recovered eosinophils from the airways after aerosol antigen challenge in sensitized mice or from the peritoneal cavities of IL-5 transgenic mice and fluorescently labeled these cells ex vivo. These labeled cells, instilled intratracheally into normal mice, migrated into draining paratracheal lymph nodes and localized to T cell-rich paracortical areas. The homing of airway eosinophils to lymph nodes was not governed by eotaxin, because CCR3(-/-) and CCR3(+/+) eosinophils migrated identically. Airway eosinophils, recovered after inhalational antigen challenge in sensitized mice, expressed MHC class II and costimulatory CD80 and CD86 proteins and functioned in vitro as CD80- and CD86-dependent, antigen-specific, antigen-presenting cells. Moreover, when instilled into the airways of antigen-sensitized recipient mice, airway eosinophils recovered after inhalational antigen challenge stimulated antigen-specific CD4(+) T cell proliferation within paratracheal lymph nodes. Thus, eosinophils within the lumina of airways can process inhaled antigens, traffic to regional lymph nodes, and function in vivo as antigen-presenting cells to stimulate responses of CD4(+) T cells.