Ariotti Silvia, Beltman Joost B, Borsje Rianne, Hoekstra Mirjam E, Halford William P, Haanen John B A G, de Boer Rob J, Schumacher Ton N M
Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands;
Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands; Theoretical Biology and Bioinformatics, Utrecht University, 3584 CH Utrecht, the Netherlands; Division of Toxicology, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, the Netherlands; and.
J Immunol. 2015 Dec 1;195(11):5285-95. doi: 10.4049/jimmunol.1500853. Epub 2015 Nov 2.
It is well established how effector T cells exit the vasculature to enter the peripheral tissues in which an infection is ongoing. However, less is known regarding how CTLs migrate toward infected cells after entry into peripheral organs. Recently, it was shown that the chemokine receptor CXCR3 on T cells has an important role in their ability to localize infected cells and to control vaccinia virus infection. However, the search strategy of T cells for virus-infected targets has not been investigated in detail and could involve chemotaxis toward infected cells, chemokinesis (i.e., increased motility) combined with CTL arrest when targets are detected, or both. In this study, we describe and analyze the migration of CTLs within HSV-1-infected epidermis in vivo. We demonstrate that activated T cells display a subtle distance-dependent chemotaxis toward clusters of infected cells and confirm that this is mediated by CXCR3 and its ligands. Although the chemotactic migration is weak, computer simulations based on short-term experimental data, combined with subsequent long-term imaging indicate that this behavior is crucial for efficient target localization and T cell accumulation at effector sites. Thus, chemotactic migration of effector T cells within peripheral tissue forms an important factor in the speed with which T cells are able to arrive at sites of infection.
效应T细胞如何离开脉管系统进入正在发生感染的外周组织，这一点已经得到了充分证实。然而，关于细胞毒性T淋巴细胞（CTL）进入外周器官后如何迁移至被感染细胞，人们了解得较少。最近有研究表明，T细胞上的趋化因子受体CXCR3在其定位被感染细胞及控制痘苗病毒感染的能力中发挥着重要作用。然而，T细胞寻找病毒感染靶标的搜索策略尚未得到详细研究，可能涉及向被感染细胞的趋化运动、趋化性运动（即运动性增加）以及在检测到靶标时CTL的停滞，或者两者兼而有之。在本研究中，我们描述并分析了CTL在体内单纯疱疹病毒1型（HSV-1）感染的表皮内的迁移情况。我们证明，活化的T细胞对被感染细胞簇表现出一种微妙的距离依赖性趋化作用，并证实这是由CXCR3及其配体介导的。尽管趋化迁移较弱，但基于短期实验数据的计算机模拟以及随后的长期成像表明，这种行为对于效应部位的有效靶标定位和T细胞聚集至关重要。因此，效应T细胞在外周组织内的趋化迁移是T细胞能够快速到达感染部位的一个重要因素。
