Department of Oncology, Microbiology, and Immunology, University of Fribourg, Fribourg, Switzerland.
Theodor Kocher Institute, University of Bern, Bern, Switzerland.
Front Immunol. 2019 Sep 6;10:2086. doi: 10.3389/fimmu.2019.02086. eCollection 2019.
T cell activation in lymphoid tissue occurs through interactions with cognate peptide-major histocompatibility complex (pMHC)-presenting dendritic cells (DCs). Intravital imaging studies using peptide-pulsed DCs have uncovered that cognate pMHC levels imprint a wide range of dynamic contacts between these two cell types. T cell-DC interactions vary between transient, "kinapse-like" contacts at low to moderate pMHC levels to immediate "synapse-like" arrest at DCs displaying high pMHC levels. To date, it remains unclear whether this pattern is recapitulated when the immune system faces a replicative agent, such as a virus, at low and high inoculum. Here, we locally administered low and high inoculum of lymphocytic choriomeningitis virus (LCMV) in mice to follow activation parameters of Ag-specific CD4 and CD8 T cells in draining lymph nodes (LNs) during the first 72 h post infection. We correlated these data with kinapse- and synapse-like motility patterns of Ag-specific T cells obtained by intravital imaging of draining LNs. Our data show that initial viral inoculum controls immediate synapse-like T cell arrest vs. continuous kinapse-like motility. This remains the case when the viral inoculum and thus the inflammatory microenvironment in draining LNs remains identical but cognate pMHC levels vary. Our data imply that the Ag-processing capacity of draining LNs is equipped to rapidly present high levels of cognate pMHC when antigenic material is abundant. Our findings further suggest that widespread T cell arrest during the first 72 h of an antimicrobial immune responses is not required to trigger proliferation. In sum, T cells adapt their scanning behavior according to available antigen levels during viral infections, with dynamic changes in motility occurring before detectable expression of early activation markers.
T 细胞在淋巴组织中的激活是通过与同源肽-主要组织相容性复合物（pMHC）呈递树突状细胞（DC）相互作用实现的。使用肽脉冲 DC 的活体成像研究揭示了同源 pMHC 水平在这两种细胞类型之间形成了广泛的动态接触。T 细胞-DC 相互作用在低至中等 pMHC 水平下变化为短暂的“kinapse 样”接触，而在高 pMHC 水平下则立即变为“synapse 样”停滞。迄今为止，当免疫系统面临低和高接种剂量的复制剂（如病毒）时，这种模式是否得到重现尚不清楚。在这里，我们在小鼠中局部给予低和高接种剂量的淋巴细胞性脉络丛脑膜炎病毒（LCMV），以在感染后 72 小时内跟踪引流淋巴结（LNs）中 Ag 特异性 CD4 和 CD8 T 细胞的激活参数。我们将这些数据与通过引流 LNs 的活体成像获得的 Ag 特异性 T 细胞的 kinapse 和 synapse 样运动模式相关联。我们的数据表明，初始病毒接种剂量控制着立即的 synapse 样 T 细胞停滞与持续的 kinapse 样运动。当病毒接种剂量和因此引流 LNs 中的炎症微环境保持相同时，但同源 pMHC 水平发生变化时，情况仍然如此。我们的数据意味着，当抗原物质丰富时，引流 LNs 的 Ag 处理能力能够迅速呈现高水平的同源 pMHC。我们的发现进一步表明，在抗菌免疫反应的最初 72 小时内，广泛的 T 细胞停滞并不需要触发增殖。总之，T 细胞在病毒感染期间根据可用抗原水平调整其扫描行为，在检测到早期激活标记物之前，其运动性发生动态变化。
