Noninvasive In Toto Imaging of the Thymus Reveals Heterogeneous Migratory Behavior of Developing T Cells
Noninvasive In Toto Imaging of the Thymus Reveals Heterogeneous Migratory Behavior of Developing T Cells
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DOI：
10.4049/jimmunol.1500361
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发表时间：
2015-09-01
影响因子：
4.4
通讯作者：
Leptin, Maria
中科院分区：
文献类型：
--
作者：
Bajoghli, Baubak;Kuri, Paola;Leptin, Maria
发育中的T细胞（胸腺细胞）在不同胸腺微环境之间的迁移对于它们的发育至关重要。胸腺组织外植体的离体研究表明胸腺细胞在胸腺中有两种不同的迁移行为。在皮质，胸腺细胞表现出随机迁移，而髓质胸腺细胞表现出有限的迁移行为。到目前为止，很难在整个胸腺中跟踪所有胸腺细胞，并将其分化步骤与其迁移动力学联系起来。要了解的空间组织的迁移行为和胸腺细胞在一个功能齐全的胸腺的发展，我们开发了转基因报告细胞系的趋化因子受体ccr9a和ccr9b，以及rag2，并使用它们的非侵入性的活成像的整个胸腺青鳉（Oryzias latipes）。我们发现，这两个趋化因子受体在青鳉幼胸腺的表达定义了两个空间上不同的胸腺细胞亚群。T细胞发育的标志性事件包括增殖、体细胞重组和胸腺选择可以映射到胸腺的亚区。每个亚群中胸腺细胞的迁移行为同样是异质的，并且特定的迁移行为与胸腺中的特定区域无关。在胸腺细胞表达rag 2期间，它们的迁移行为更加均一。因此，胸腺细胞的迁移行为部分与其发育阶段相关，而不是由其空间定位所定义。
The migration of developing T cells (thymocytes) between distinct thymic microenvironments is crucial for their development. Ex vivo studies of thymus tissue explants suggest two distinct migratory behaviors of thymocytes in the thymus. In the cortex, thymocytes exhibit a stochastic migration, whereas medullary thymocytes show confined migratory behavior. Thus far, it has been difficult to follow all thymocytes in an entire thymus and relate their differentiation steps to their migratory dynamics. To understand the spatial organization of the migratory behavior and development of thymocytes in a fully functional thymus, we developed transgenic reporter lines for the chemokine receptors ccr9a and ccr9b, as well as for rag2, and used them for noninvasive live imaging of the entire thymus in medaka (Oryzias latipes). We found that the expression of these two chemokine receptors in the medaka juvenile thymus defined two spatially distinct subpopulations of thymocytes. Landmark events of T cell development including proliferation, somatic recombination, and thymic selection can be mapped to subregions of the thymus. The migratory behavior of thymocytes within each of the subpopulations is equally heterogeneous, and specific migratory behaviors are not associated with particular domains in the thymus. During the period when thymocytes express rag2 their migratory behavior was more homogeneous. Therefore, the migratory behavior of thymocytes is partly correlated with their developmental stage rather than being defined by their spatial localization.