Yamashita M, Hashimoto K, Kimura M, Kubo M, Tada T, Nakayama T
Research Institute for Biological Sciences, Science University of Tokyo, Noda City, Chiba, Japan.
Int Immunol. 1998 May;10(5):577-91. doi: 10.1093/intimm/10.5.577.
The lymphocyte-specific protein tyrosine kinase p56(lck) (Lck) is well documented with regard to its role in regulating T cell activation and thymocyte development through delivery of signals via the mature alphabeta TCR as well as the pre-TCR. Little is known, however, about the role of Lck in Th cell subset differentiation in the periphery. Here, we assess the requirement for tyrosine kinase activation of Lck in Th1 and Th2 cell differentiation by using a dominant-negative Lck (DLGKR) transgenic (Tg) mice under the control of a lck distal promoter that directs high expression in mature T cells, in which splenic CD4 T cells developed normally. This Tg mouse provides a good experimental model system to investigate the roles of Lck in mature T cell function in vivo. We show that the catalytically inactive Lck protein at about twice-normal concentrations inhibits Th2 subset differentiation in vivo and in vitro, whilst leaving the maturation of the other T cell subset, Th1, intact. These data indicate a requirement for Lck activity in Th2 cell differentiation, and a differential dependence for Lck activity between Th2 and Th1 cell differentiation.
淋巴细胞特异性蛋白酪氨酸激酶p56(lck)(Lck)在通过成熟的αβTCR以及前TCR传递信号来调节T细胞活化和胸腺细胞发育方面已有充分的文献记载。然而，关于Lck在外周Th细胞亚群分化中的作用却知之甚少。在此，我们通过使用在lck远端启动子控制下的显性负性Lck(DLGKR)转基因(Tg)小鼠来评估Lck的酪氨酸激酶激活在Th1和Th2细胞分化中的必要性，该启动子在成熟T细胞中指导高表达，其中脾脏CD4 T细胞正常发育。这种Tg小鼠为研究Lck在体内成熟T细胞功能中的作用提供了一个良好的实验模型系统。我们发现，大约两倍于正常浓度的催化失活Lck蛋白在体内和体外均抑制Th2亚群分化，而其他T细胞亚群Th1的成熟则不受影响。这些数据表明Th2细胞分化需要Lck活性，并且Th2和Th1细胞分化对Lck活性的依赖性存在差异。
