Cho Ok Hyun, Shin Hyun Mu, Miele Lucio, Golde Todd E, Fauq Abdul, Minter Lisa M, Osborne Barbara A
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
J Immunol. 2009 Mar 15;182(6):3380-9. doi: 10.4049/jimmunol.0802598.
The maturation of naive CD8(+) T cells into effector CTLs is a critical feature of a functional adaptive immune system. Development of CTLs depends, in part, upon the expression of the transcriptional regulator eomesodermin (EOMES), which is thought to regulate expression of two key effector molecules, perforin and granzyme B. Although EOMES is important for effector CTL development, the precise mechanisms regulating CD8(+) effector cell maturation remains poorly understood. In this study, we show that Notch1 regulates the expression of EOMES, perforin, and granzyme B through direct binding to the promoters of these crucial effector molecules. By abrogating Notch signaling, both biochemically as well as genetically, we conclude that Notch activity mediates CTL activity through direct regulation of EOMES, perforin, and granzyme B.
初始CD8(+) T细胞成熟为效应性细胞毒性T淋巴细胞（CTL）是功能性适应性免疫系统的一个关键特征。CTL的发育部分依赖于转录调节因子中胚层决定因子（EOMES）的表达，EOMES被认为可调节两种关键效应分子穿孔素和颗粒酶B的表达。尽管EOMES对效应性CTL的发育很重要，但调节CD8(+)效应细胞成熟的精确机制仍知之甚少。在本研究中，我们表明Notch1通过直接结合这些关键效应分子的启动子来调节EOMES、穿孔素和颗粒酶B的表达。通过生物化学和遗传学方法消除Notch信号，我们得出结论，Notch活性通过直接调节EOMES、穿孔素和颗粒酶B来介导CTL活性。
