Calcium oscillations regulate thymocyte motility during positive selection in the three-dimensional thymic environment
Calcium oscillations regulate thymocyte motility during positive selection in the three-dimensional thymic environment
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DOI：
10.1038/ni1161
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发表时间：
2005-02-01
影响因子：
30.5
通讯作者：
Lewis, RS
中科院分区：
文献类型：
--
作者：
Bhakta, NR;Oh, DY;Lewis, RS
三维胸腺微环境和钙信号通路是驱动发育中的T细胞正向选择的必要条件。然而，钙信号的性质及其在胸腺中作用的多样性尚不清楚。我们在这里描述了一种胸腺切片的制备，用于用双光子显微镜实时观察胸腺细胞的运动和信号。初始胸腺细胞在低细胞内钙浓度下具有高度运动性，但在正选择过程中，细胞变得不动，并表现出持续的钙浓度振荡。增加的细胞内钙是必要的，足以阻止胸腺细胞的运动。运动的钙依赖性延长了胸腺细胞与携带抗原的基质细胞的相互作用，促进了持续的信号传导，可能增强了正选择基因的表达。
The three-dimensional thymic microenvironment and calcium signaling pathways are essential for driving positive selection of developing T cells. However, the nature of calcium signals and the diversity of their effects in the thymus are unknown. We describe here a thymic slice preparation for visualizing thymocyte motility and signaling in real time with two-photon microscopy. Naive thymocytes were highly motile at low intracellular calcium concentrations, but during positive selection cells became immobile and showed sustained calcium concentration oscillations. Increased intracellular calcium was necessary and sufficient to arrest thymocyte motility. The calcium dependence of motility acts to prolong thymocyte interactions with antigen-bearing stromal cells, promoting sustained signaling that may enhance the expression of genes underlying positive selection.