Requirements for T lymphocyte migration in explanted lymph nodes
Requirements for T lymphocyte migration in explanted lymph nodes
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DOI：
10.4049/jimmunol.178.12.7747
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发表时间：
2007-06-15
影响因子：
4.4
通讯作者：
Dustin, Michael L.
中科院分区：
文献类型：
--
作者：
Huang, Julie H.;Cardenas-Navia, L. Isabel;Dustin, Michael L.
虽然T淋巴细胞归巢淋巴结（LN）的要求是很好的研究，少得多的是已知的淋巴结内T淋巴细胞运动的要求。成像小鼠T淋巴细胞迁移在rected LN使用双光子激光扫描荧光显微镜提供了一个机会，系统地研究这些要求。我们已经开发了一个封闭的系统，用于在控制温度、氧合和灌注率的情况下对完整的LN进行成像。LN深层副皮质中的幼稚T淋巴细胞运动需要> 13 μ m/s的灌注速率和> 7.4%的O-2分压（pO（2））。幼稚T淋巴细胞的运动在被膜下区域慢38%，并有较高的转踝和逮捕系数比幼稚T淋巴细胞在深副皮质。T淋巴细胞活化降低了对pO（2）的需求，但也降低了运动的速度。深副皮质区尽管CCR 7（-/-）初始T细胞在运动中表现出小幅降低，但百日咳毒素全身治疗使初始T淋巴细胞速度降低了59%，表明G α（1）介导的信号传导的贡献，但除CCR 7外还涉及其他G蛋白偶联受体。腺苷、PG/脂氧合酶、溶血磷脂酰胆碱和鞘氨醇-1-磷酸途径中的受体敲除或药理学抑制并未单独改变幼稚T细胞迁移。这些数据表明pO（2）、组织结构和G蛋白偶联受体信号在淋巴结转移中调节幼稚T淋巴细胞迁移。
Although the requirements for T lymphocyte homing to lymph nodes (LNs) are well studied, much less is known about the requirements for T lymphocyte locomotion within LNs. Imaging of murine T lymphocyte migration in explanted LNs using two-photon laser-scanning fluorescence microscopy provides an opportunity to systematically study these requirements. We have developed a closed system for imaging an intact LN with controlled temperature, oxygenation, and perfusion rate. Naive T lymphocyte locomotion in the deep paracortex of the LN required a perfusion rate of > 13 mu m/s and a partial pressure of O-2 (pO(2)) of >7.4%. Naive T lymphocyte locomotion in the subcapsular region was 38% slower and had higher turning ankles and arrest coefficients than naive T lymphocytes in the deep paracortex. T lymphocyte activation decreased the requirement for pO(2), but also decreased the speed of locomotion in the. deep paracortex. Although CCR7(-/-) naive T cells displayed a small reduction in locomotion, systemic treatment with pertussis toxin reduced naive T lymphocyte speed by 59%, indicating a contribution of G alpha(1)-mediated signaling, but involvement of other G protein-coupled receptors besides CCR7. Receptor knockouts or pharmacological inhibition in the adenosine, PG/lipoxygenase, lysophosphatidylcholine, and sphingosine-1-phosphate pathways did not individually alter naive T cell migration. These data implicate pO(2), tissue architecture, and G-protein coupled receptor signaling in regulation of naive T lymphocyte migration in explanted LNs.