Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy
Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy
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DOI：
10.1073/pnas.2628040100
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发表时间：
2003-03-04
影响因子：
11.1
通讯作者：
Parker, I
中科院分区：
文献类型：
--
作者：
Miller, MJ;Wei, SH;Parker, I
T细胞在血液和次级淋巴器官之间的再循环需要T细胞是能动的并且对组织特异性信号敏感。T细胞运动性已经在体外进行了研究，但单个T细胞在体内的迁移行为仍然是个谜。在这里，我们使用活体双光子激光显微镜，对麻醉小鼠腹股沟淋巴结中初始CD 4（+）T细胞的运动和运输进行了成像。淋巴结深处的活体记录显示T细胞在微血管中快速流动，并捕获了个体归巢事件。在弥漫性皮质内，T细胞显示出强有力的运动，平均运动速度约为11 mum·min（-1）。T细胞大约每2分钟在低运动性和高运动性状态之间循环，达到峰值速度>25 mum·min（-1）。对3D空间中T细胞迁移的分析揭示了类似于随机游走的默认运输程序。我们的研究结果表明，幼稚T细胞不会集体迁移，因为它们可能在广泛的趋化因子梯度的指导下。相反，他们似乎迁移作为自主代理，每个细胞采取一个独立的traffickingpath. We的结果呼吁质疑的作用，趋化因子梯度的基础T细胞内的T细胞区域的运输，并建议抗原检测可能会导致从一个随机过程，通过随机游走促进接触抗原呈递树突状细胞。
The recirculation of T cells between the blood and secondary lymphoid organs requires that T cells are motile and sensitive to tissue-specific signals. T cell motility has been studied in vitro, but the migratory behavior of individual T cells in vivo has remained enigmatic. Here, using intravital two-photon laser microscopy, we imaged the locomotion and trafficking of naive CD4(+) T cells in the inguinal lymph nodes of anesthetized mice. Intravital recordings deep within the lymph node showed T cells flowing rapidly in the microvasculature and captured individual homing events. Within the diffuse cortex, T cells displayed robust motility with an average velocity of approximate to11 mum-min(-1). T cells cycled between states of low and high motility roughly every 2 min, achieving peak velocities >25 mum-min(-1). An analysis of T cell migration in 3D space revealed a default trafficking program analogous to a random walk. Our results show that naive T cells do not migrate collectively, as they might under the direction of pervasive chemokine gradients. Instead, they appear to migrate as autonomous agents, each cell taking an independent trafficking path. Our results call into question the role of chemokine gradients for basal T cell trafficking within T cell areas and suggest that antigen detection may result from a stochastic process through which a random walk facilitates contact with antigen-presenting dendritic cells.