Britschgi Mirjam R, Link Alexander, Lissandrin Tonje Katrine A, Luther Sanjiv A
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
J Immunol. 2008 Dec 1;181(11):7681-8. doi: 10.4049/jimmunol.181.11.7681.
The chemokine receptor CCR7 is critical for the recirculation of naive T cells. It is required for T cell entry into secondary lymphoid organs (SLO) and for T cell motility and retention within these organs. How CCR7 activity is regulated during these processes in vivo is poorly understood. Here we show strong modulation of CCR7 surface expression and occupancy by the two CCR7 ligands, both in vitro and in vivo. In contrast to blood, T cells in SLO had most surface CCR7 occupied with CCL19, presumably leading to continuous signaling and cell motility. Both ligands triggered CCR7 internalization in vivo as shown in Ccl19(-/-) and plt/plt mice. Importantly, CCR7 occupancy and down-regulation led to strongly impaired chemotactic responses, an effect reversible by CCR7 resensitization. Therefore, during their recirculation, T cells cycle between states of free CCR7 with high ligand sensitivity in blood and occupied CCR7 associated with continual signaling and reduced ligand sensitivity within SLO. We propose that these two states of CCR7 are important to allow the various functions CCR7 plays in T cell recirculation.
趋化因子受体CCR7对初始T细胞的再循环至关重要。它是T细胞进入次级淋巴器官（SLO）以及T细胞在这些器官内运动和滞留所必需的。目前对CCR7活性在体内这些过程中是如何被调控的了解甚少。在此我们展示了在体外和体内，CCR7的两种配体对CCR7表面表达和占有率有强烈的调节作用。与血液中的T细胞相比，SLO中的T细胞表面大部分CCR7被CCL19占据，这可能导致持续的信号传导和细胞运动。如在Ccl19(-/-)和plt/plt小鼠中所示，两种配体在体内均触发CCR7内化。重要的是，CCR7占有率和下调导致趋化反应严重受损，这种效应可通过CCR7再敏化逆转。因此，在再循环过程中，T细胞在血液中具有高配体敏感性的游离CCR7状态与SLO内与持续信号传导及降低的配体敏感性相关的被占据的CCR7状态之间循环。我们提出CCR7的这两种状态对于CCR7在T细胞再循环中发挥的各种功能很重要。
