Cellular dyntarnics and migration during T-Iympharyle development and selection in the thymus

T淋巴细胞是在区分非我和自我方面发挥重要作用的细胞。T淋巴细胞通过在胸腺发育过程中形成识别特异库而获得这种能力，这一过程被称为正向选择和负向选择。关于T淋巴细胞发育过程中的抗原受体信号如何在正反向选择中控制细胞命运，已经有了很大的揭示。然而，T淋巴细胞是如何在胸腺环境中产生和选择的仍然知之甚少。目前的研究表明，趋化因子受体CCR7和CCR9双重缺陷的小鼠在胸腺血管形成之前而不是在胸腺血管形成之后，在胎儿胸腺的定植方面存在特异性缺陷。先天血管缺陷的胎儿胸腺定植后，选择性地失去了第一波T细胞发育，产生了表皮Vγ3(+)γδT细胞。出乎意料的是，CCL21，一个CCR7配体，不是通过依赖foxn1的胸腺原基表达的，而是由Gcm2…表达的而CCR9配体CCL25主要由依赖Foxn1的胸腺原基表达，揭示了相邻的甲状旁腺在引导胎儿胸腺定植中的作用。这些结果表明，依赖Gcm2的甲状旁腺和依赖Foxn1的胸腺原基在建立CCL21/CCR7和CCL25/CCR9介导的趋化因子导向方面相互协调，对于血管前胎儿胸腺定植是必不可少的。这项研究还表明，在未成熟淋巴细胞特异性RAGL的控制下，非侵入性检测到了表达荧光蛋白的转基因青竹中的胸腺细胞。我们发现淋巴祖细胞以前后位定向特异性和多种趋化因子依赖的方式在胸腺原基定植，揭示了胸腺外前趋化成分引导血管胸腺前定植。我们还发现，发育中的胸腺细胞在抗原受体和辅受体表达的同时获得了随机行走的运动，这表明胸腺细胞行走是在发育阶段开始的，以进行曲谱选择。因此，这项研究首次实现了胸腺细胞的实时活体成像，而不需要手术干预。较少

T lymphocytes are the cells that play an essential role in distinguishing non-self from self. T lymphocytes acquire this ability through shaping a repertoire of recognition specificity during the development in the thymus, by the process referred to as positive and negative selection. Much has been revealed regarding how antigen-receptor signals in developing T lymphocytes control cell fate upon positive and negative selection. However, how T lymphocytes are generated and selected in the thymus environment is still poorly understood. The present study showed that mice doubly deficient for chemokine receptors CCR7 and CCR9 were defective specifically in fetal thymus colonization before, but not after, thymus vascularization. The defective prevascular fetal thymus colonization was followed by selective loss of the first wave of T-cell development generating epidermal Vγ3(+) γδ T cells. Unexpectedly, CCL21, a CCR7 ligand, was expressed not by Foxn1 -dependent thymic primordium but by Gcm2 … More -dependent parathyroid primordium, whereas CCL25, a CCR9 ligand, was predominantly expressed by Foxn1 -dependent thymic primordium, revealing the role of the adjacent parathyroid in guiding fetal thymus colonization. These results indicate coordination between Gcm2-dependent parathyroid and Foxn1 -dependent thymic primordia in establishing CCL21/CCR7- and CCL25/CCR9-mediated chemokine guidance essential for prevascular fetal thymus colonization. This study also showed the noninvasive detection of thymocytes in transgenic medaka that express fluorescent protein under the control of immature-lymphocyte-specific ragl. We showed that lymphoid progenitor cells colonized the thymus primordium in an anterior-to-posterior orientation-specific and multiple-chemokine-dependent manner, revealing that extrathymic anterior chemotactic components guide prevascular thymus colonization. We also show that developing thymocytes acquire the random walk motility along with the expression of antigen receptors and coreceptors, suggesting that thymocyte walking is initiated at the developmental stage for repertoire selection. Thus, this study for the first time enabled real-time intravital imaging of thymocytes without surgical invasion. Less