Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 2M1, Canada.
J Exp Med. 2010 Jul 5;207(7):1435-51. doi: 10.1084/jem.20091373. Epub 2010 Jun 14.
Antiinfluenza type 2 (T2) immunity contributes to both immunopathology and immunoprotection, yet the underlying mechanisms modulating T2 immunity remain ill defined. We describe a novel mouse antigen (Ag)-presenting cell (APC), designated late-activator APC (LAPC). After pulmonary influenza A (H1N1) virus infection, LAPCs enter the lungs, capture viral Ag, and subsequently migrate to the draining lymph node (DLN) and spleen, with delayed kinetics relative to dendritic cells (DCs). In the DLN, influenza virus-activated LAPCs present Ag and selectively induce T helper type 2 (Th2) effector cell polarization by cell-cell contact-mediated modulation of GATA-3 expression. In adoptive transfer experiments, influenza virus-activated LAPCs augmented Th2 effector T cell responses in the DLN, increased production of circulating antiinfluenza immunoglobulin, and increased levels of T2 cytokines in bronchoalveolar lavage fluid in recipient influenza virus-infected mice. LAPC-recipient mice exhibited exacerbated pulmonary pathology, with delayed viral clearance and enhanced pulmonary eosinophilia. Collectively, our results identify and highlight the importance of LAPCs as immunomodulators of T2 immunity during influenza A virus infection.
抗 2 型流感（T2）免疫既能导致免疫病理，也能提供免疫保护，但调节 T2 免疫的潜在机制仍不清楚。我们描述了一种新型的小鼠抗原（Ag）呈递细胞（APC），称为晚期激活 APC（LAPC）。在肺部流感 A（H1N1）病毒感染后，LAPCs 进入肺部，捕获病毒 Ag，随后迁移到引流淋巴结（DLN）和脾脏，其动力学相对于树突状细胞（DCs）延迟。在 DLN 中，流感病毒激活的 LAPCs 通过细胞-细胞接触介导的 GATA-3 表达调控来呈递 Ag，并选择性地诱导 T 辅助 2（Th2）效应细胞极化。在过继转移实验中，流感病毒激活的 LAPCs 增强了 DLN 中的 Th2 效应 T 细胞反应，增加了循环抗流感免疫球蛋白的产生，并增加了受体流感病毒感染小鼠支气管肺泡灌洗液中 T2 细胞因子的水平。LAPC 受体小鼠表现出更严重的肺部病理，病毒清除延迟，肺部嗜酸性粒细胞增多。总之，我们的研究结果确定并强调了 LAPCs 在流感 A 病毒感染期间作为 T2 免疫调节剂的重要性。
