Molecular signals that regulate the development and movements of developing T lymphocytes

调节胸腺中T淋巴细胞的发育和选择的信号已被研究。我们发现T细胞受体介导的信号激活Akt，Akt使Nur77磷酸化，从而拮抗Nur77介导的T细胞凋亡，这表明T细胞受体介导的阳性和阴性选择可以通过Akt介导的Nur77磷酸化来控制。我们还发现胸腺上皮细胞中的Stat3基因被角蛋白5启动子特异性破坏的小鼠发生了严重的胸腺发育不全，并表现出胸腺对次最佳剂量的地塞米松或γ射线的高度敏感性，表明胸腺上皮细胞中的Stat3在维持胸腺结构和胸腺细胞存活中起着重要作用。此外，我们已经发现，CCR7配体趋化因子CCL19吸引成熟的T细胞的胎儿胸腺器官培养，和新生儿的循环T细胞的外观是有缺陷的CCR7缺陷的小鼠，表明CCR7依赖的途径胸腺移民代表了一个主要的途径新生儿T细胞输出。

Signals that regulate the development and selection of T lymphocytes in the thymus have been studied. We have found that T-cell receptor-mediated signals activated Akt, which phosphorylated Nur77 and thereby antagonized Nur77-mediated apoptosis of T cells, suggesting that T-cell receptor-mediated positive and negative selection can be controlled by Akt-mediated phophorylation of Nur77. We have also found that the mice in which Stat3 gene in thymic epithelial cells has been specifically disrupted by the keratin 5 promoter developed severe thymic hypoplasia and exhibited a high susceptibility of the thymus to suboptimal doses of dexamethasone or gamma-irradiation, indicating that Stat3 in thymic epithelial cells plays an essential role in maintaining thymic architecture and thymocyte survival. Moreover, we have found that CCR7-ligand chemokine CCL19 attracted mature T cells out of the fetal thymus organ culture, and that neonatal appearance of circulating T cells was defective in CCR7-deficient mice, indicating that CCR7-dependent pathway of thymic emigration represents a major pathway of neonatal T cell export.