Department of Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
Int J Mol Sci. 2021 Jul 14;22(14):7522. doi: 10.3390/ijms22147522.
During influenza A virus (IAV) infections, CD4 T cell responses within infected lungs mainly involve T helper 1 (Th1) and regulatory T cells (Tregs). Th1-mediated responses favor the co-expression of T-box transcription factor 21 (T-bet) in Foxp3 Tregs, enabling the efficient Treg control of Th1 responses in infected tissues. So far, the exact accumulation kinetics of T cell subsets in the lungs and lung-draining lymph nodes (dLN) of IAV-infected mice is incompletely understood, and the epigenetic signature of Tregs accumulating in infected lungs has not been investigated. Here, we report that the total T cell and the two-step Treg accumulation in IAV-infected lungs is transient, whereas the change in the ratio of CD4 to CD8 T cells is more durable. Within lungs, the frequency of Tregs co-expressing T-bet is steadily, yet transiently, increasing with a peak at Day 7 post-infection. Interestingly, T-bet Tregs accumulating in IAV-infected lungs displayed a strongly demethylated locus, similarly as in T-bet conventional T cells, and a fully demethylated Treg-specific demethylated region (TSDR) within the locus. In summary, our data suggest that T-bet but not T-bet Tregs are epigenetically stabilized during IAV-induced infection in the lung.
在甲型流感病毒（IAV）感染期间，感染肺部的 CD4 T 细胞反应主要涉及辅助性 T 细胞 1（Th1）和调节性 T 细胞（Tregs）。Th1 介导的反应有利于 Foxp3 Tregs 中 T 框转录因子 21（T-bet）的共表达，从而使 Treg 能够有效地控制感染组织中的 Th1 反应。到目前为止，IAV 感染小鼠肺部和引流淋巴结（dLN）中 T 细胞亚群的确切积累动力学尚不完全清楚，而且在感染肺部积累的 Tregs 的表观遗传特征尚未得到研究。在这里，我们报告说，IAV 感染肺部的总 T 细胞和两步 Treg 积累是短暂的，而 CD4 与 CD8 T 细胞比值的变化则更持久。在肺部，共表达 T-bet 的 Tregs 的频率持续但短暂地增加，在感染后第 7 天达到峰值。有趣的是，在 IAV 感染的肺部中积累的 T-bet Tregs 表现出强烈去甲基化的 基因座，与 T-bet 常规 T 细胞类似，并且在 基因座内具有完全去甲基化的 Treg 特异性去甲基化区域（TSDR）。总之，我们的数据表明，在 IAV 诱导的肺部感染中，T-bet 而不是 T-bet Tregs 是通过表观遗传稳定的。
