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

T淋巴细胞是在区分非自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性的库来获得这种能力，这一过程被称为阳性和阴性选择。关于抗原受体信号在发育中的T淋巴细胞中如何控制细胞在正选择和负选择时的命运，已经揭示了很多。然而，T淋巴细胞如何在胸腺环境中产生和选择仍然知之甚少。目前的研究表明，小鼠趋化因子受体CCR 7和CCR 9的双重缺陷是缺陷，特别是在胎儿胸腺定植之前，但不是之后，胸腺血管化。有缺陷的血管前胎儿胸腺定殖之后，产生表皮Vγ3（+）γδ T细胞的T细胞发育的第一波选择性丧失。出乎意料的是，CCR 7配体CCL 21不是由Foxn 1依赖的胸腺原基表达，而是由Gcm 2表达 关于我们 依赖的甲状旁腺原基，而CCL 25，CCR 9配体，主要由Foxn 1依赖的胸腺原基表达，揭示了相邻的甲状旁腺在指导胎儿胸腺定植的作用。这些结果表明Gcm 2依赖性甲状旁腺和Foxn 1依赖性胸腺原基之间的协调，建立CCL 21/CCR 7-和CCL 25/CCR 9-介导的趋化因子的指导血管前胎儿胸腺定殖必不可少。本研究还显示了非侵入性检测转基因青鳉胸腺细胞表达的荧光蛋白的控制下，未成熟淋巴细胞特异性的ragl。我们发现，淋巴祖细胞殖民胸腺原基的前向后方向特异性和多种趋化因子依赖的方式，揭示胸腺外前趋化成分引导血管前胸腺殖民。我们还表明，发展中的胸腺细胞获得随机行走运动沿着与抗原受体和辅助受体的表达，表明胸腺细胞行走开始在发展阶段的剧目选择。因此，这项研究首次实现了胸腺细胞的实时活体成像，而无需手术侵入。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