CD8⁺ T cell responses to pulmonary challenges are primed by lung migratory dendritic cells (mDCs), which capture antigens in the lungs and migrate to the lung-draining mediastinal lymph node (med-LN) to activate T cells. The lungs and the spleen are not connected by the lymphatic vasculature. Thus, the current paradigm suggests that, in response to respiratory virus infections that are restricted to the respiratory tract, priming of T cell responses by lung mDCs takes place entirely in the med-LN. Our results challenge this “LN-centric” paradigm by demonstrating that, during influenza virus infection, lung mDCs egress the med-LN and traffic to the spleen, where they prime influenza-specific CD8⁺ T cells. CD8⁺ T cells primed in the spleen are transcriptionally distinct and have enhanced ability to differentiate into long-lived memory cells compared with med-LN–primed counterparts. Thus, our data identify a lung mDC trafficking pathway that connects the lungs with the spleen.

中文翻译：

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流感感染后肺树突细胞迁移到脾脏以启动长寿命 TCF1hi 记忆 CD8+ T 细胞前体

CD8 ⁺ T 细胞对肺部挑战的反应由肺迁移树突状细胞 (mDC) 引发，mDC 在肺部捕获抗原并迁移到肺引流纵隔淋巴结 (med-LN) 以激活 T 细胞。肺和脾不通过淋巴脉管系统连接。因此，目前的范式表明，为了应对仅限于呼吸道的呼吸道病毒感染，肺 mDC 引发的 T 细胞反应完全发生在 med-LN 中。我们的结果通过证明，在流感病毒感染期间，肺 mDC 离开 med-LN 并进入脾脏，在那里它们引发流感特异性 CD8 ⁺ T 细胞，从而挑战了这种“以 LN 为中心”的范式。CD8 ⁺与 med-LN 引发的对应物相比，在脾脏中引发的 T 细胞在转录上是不同的，并且具有增强的分化成长寿记忆细胞的能力。因此，我们的数据确定了将肺与脾连接起来的肺 mDC 运输途径。