Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Front Immunol. 2019 Mar 7;10:400. doi: 10.3389/fimmu.2019.00400. eCollection 2019.
Tissue-resident memory CD8 T (T) cells that develop in the epithelia at portals of pathogen entry are important for improved protection against re-infection. CD8 T cells within the skin and the small intestine are long-lived and maintained independently of circulating memory CD8 T cells. In contrast to CD8 T cells at these sites, CD8 T cells that arise after influenza virus infection within the lungs display high turnover and require constant recruitment from the circulating memory pool for long-term persistence. The distinct characteristics of CD8 T cell maintenance within the lungs may suggest a unique program of transcriptional regulation of influenza-specific CD8 T cells. We have previously demonstrated that the transcription factors Hobit and Blimp-1 are essential for the formation of CD8 T cells across several tissues, including skin, liver, kidneys, and the small intestine. Here, we addressed the roles of Hobit and Blimp-1 in CD8 T cell differentiation in the lungs after influenza infection using mice deficient for these transcription factors. Hobit was not required for the formation of influenza-specific CD8 T cells in the lungs. In contrast, Blimp-1 was essential for the differentiation of lung CD8 T cells and inhibited the differentiation of central memory CD8 T (T) cells. We conclude that Blimp-1 rather than Hobit mediates the formation of CD8 T cells in the lungs, potentially through control of the lineage choice between T and T cells during the differentiation of influenza-specific CD8 T cells.
组织驻留记忆 CD8 T(T)细胞在病原体进入的上皮细胞中发育,对于改善再次感染的保护作用非常重要。皮肤和小肠内的 CD8 T 细胞是长寿的,并且独立于循环记忆 CD8 T 细胞维持。与这些部位的 CD8 T 细胞相反,在肺部感染流感病毒后产生的 CD8 T 细胞具有高周转率,并且需要从循环记忆池中不断招募以维持长期存在。肺部 CD8 T 细胞维持的独特特征可能表明流感特异性 CD8 T 细胞的转录调控存在独特的程序。我们之前已经证明,转录因子 Hobit 和 Blimp-1 对于包括皮肤、肝脏、肾脏和小肠在内的多个组织中 CD8 T 细胞的形成是必不可少的。在这里,我们使用缺乏这些转录因子的小鼠,研究了 Hobit 和 Blimp-1 在流感感染后肺部 CD8 T 细胞分化中的作用。Hobit 对于肺部流感特异性 CD8 T 细胞的形成不是必需的。相比之下,Blimp-1 对于肺 CD8 T 细胞的分化是必不可少的,并且抑制中央记忆 CD8 T(T)细胞的分化。我们得出结论,Blimp-1 而不是 Hobit 介导肺部 CD8 T 细胞的形成,可能是通过在流感特异性 CD8 T 细胞分化过程中控制 T 和 T 细胞之间的谱系选择。