Zhong Xiao-Ping, Hainey Ehmonie A, Olenchock Benjamin A, Jordan Martha S, Maltzman Jonathan S, Nichols Kim E, Shen Hao, Koretzky Gary A
The Signal Transduction Program, The Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania 19104, USA.
Nat Immunol. 2003 Sep;4(9):882-90. doi: 10.1038/ni958. Epub 2003 Jul 27.
Much is known about how T cell receptor (TCR) engagement leads to T cell activation; however, the mechanisms terminating TCR signaling remain less clear. Diacylglycerol, generated after TCR ligation, is essential in T cells. Its function must be controlled tightly to maintain normal T cell homeostasis. Previous studies have shown that diacylglycerol kinase zeta (DGKzeta), which converts diacylglycerol to phosphatidic acid, can inhibit TCR signaling. Here we show that DGKzeta-deficient T cells are hyperresponsive to TCR stimulation both ex vivo and in vivo. Furthermore, DGKzeta-deficient mice mounted a more robust immune response to lymphocytic choriomeningitis virus infection than did wild-type mice. These results demonstrate the importance of DGKzeta as a physiological negative regulator of TCR signaling and T cell activation.
关于T细胞受体（TCR）激活如何导致T细胞活化，我们已经了解很多；然而，终止TCR信号传导的机制仍不太清楚。TCR连接后产生的二酰基甘油在T细胞中至关重要。其功能必须受到严格控制以维持正常的T细胞内环境稳定。先前的研究表明，将二酰基甘油转化为磷脂酸的二酰基甘油激酶ζ（DGKζ）可以抑制TCR信号传导。在这里，我们表明，缺乏DGKζ的T细胞在体外和体内对TCR刺激的反应都过度活跃。此外，与野生型小鼠相比，缺乏DGKζ的小鼠对淋巴细胞性脉络丛脑膜炎病毒感染产生了更强有力的免疫反应。这些结果证明了DGKζ作为TCR信号传导和T细胞活化的生理性负调节因子的重要性。
