Shi H Z, Humbles A, Gerard C, Jin Z, Weller P F
Department of Medicine, Harvard Thorndike Laboratories, Charles A. Dana Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
J Clin Invest. 2000 Apr;105(7):945-53. doi: 10.1172/JCI8945.
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.
由于在过敏性疾病中募集到气道中的嗜酸性粒细胞会接触吸入性变应原，我们评估了支气管腔内的嗜酸性粒细胞在体内是否能作为吸入性抗原的抗原呈递细胞发挥作用。我们在致敏小鼠经气溶胶抗原激发后从气道中回收嗜酸性粒细胞，或从白细胞介素-5转基因小鼠的腹腔中回收嗜酸性粒细胞，并在体外对这些细胞进行荧光标记。将这些标记细胞经气管内注入正常小鼠后，它们迁移至引流的气管旁淋巴结，并定位于富含T细胞的副皮质区。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调控，因为CCR3(-/-)和CCR3(+/+)嗜酸性粒细胞的迁移情况相同。在致敏小鼠经吸入性抗原激发后回收的气道嗜酸性粒细胞表达MHC II类分子以及共刺激分子CD80和CD86蛋白，并在体外作为依赖CD80和CD86的、抗原特异性的抗原呈递细胞发挥作用。此外，当将经吸入性抗原激发后回收的气道嗜酸性粒细胞注入抗原致敏的受体小鼠气道时，它们会刺激气管旁淋巴结内抗原特异性CD4(+) T细胞增殖。因此，气道腔内的嗜酸性粒细胞能够处理吸入性抗原，迁移至局部淋巴结，并在体内作为抗原呈递细胞发挥作用，以刺激CD4(+) T细胞反应。
