IN VIVO ANALYSIS OF INTRACELLULAR SIGNALS CONTROLLING LYMPHOCYTE

虽然T细胞抗原受体（TCR）和其他共受体传递的信号在早期T细胞发育中起着至关重要的作用，但这些信号是如何在细胞内调节的仍有待阐明。我们已经确定原癌蛋白Cbl是TCR信号的负调节因子，并在胸腺选择过程中生理调节TCR信号阈值。这些结果首次证明，原癌蛋白Cbl在生理上有助于小鼠胸腺选择和功能性T细胞群的建立。同时检测活化的T细胞及其在体内的运动在技术上是困难的。我们已经建立了一个报告小鼠系，其中激活的产生IL-2的T细胞可以很容易地通过插入IL-2基因位点的GFP标记来监测。该小鼠模型为我们提供了一种强大的方法来非破坏性地鉴定产生IL-2的T细胞，并在体外和体内跟踪其随后的分化命运。- TCR信号，接头分子，Cbl，胸腺选择，T细胞发育，IL-2基因表达，GFP报告基因，基因靶向。

While signals delivered by the T cell antigen receptor (TCR) and other co-receptors play an essential role for early T cell development, it remains to be clarified as to how are these signals modulated intracellularly. We have identified that the proto-oncoprotein Cbl is a negative regulator for TCR signaling, and physiologically regulates the TCR signalling threshold during thymic selection. These results provide first evidence that proto-onco protein Cbl physiologically contributes to the thymic selection and establishment of the functional T cell population in mice. It has been technically difficult to simultaneously detect the activated T cells and their movement in vivo. We have established a reporter mouse line in which the activated IL-2 producing T cells can be readily monitored by a GFP marker inserted into its IL-2 gene locus. This mouse model provides us a powerful approach to non- destructively identify IL-2 producing T cells and follow their subsequent differentiation fate both in vitro and in vivo. - TCR signaling, adaptor molecule, Cbl, thymic selection, T cell development, IL-2 gene expression, GFP reporter, gene targeting.