Nature Immunology：发现一种T细胞何时出击的机制 - 生物研究-生物谷

杀伤性Ｔ细胞是一种重要的免疫细胞，能够破坏被病毒感染或癌变的细胞，日本专家在25日的《自然·免疫学》杂志网络版上发表报告说，他们发现了杀伤性Ｔ细胞是如何确定出击时机的。    

杀伤性Ｔ细胞是白细胞的一种，它们担负着向出现异常的细胞内注入分解酶，破坏这些异常细胞的任务，但杀伤性Ｔ细胞发挥这种功能的具体机制一直不明。  

日 本德岛大学教授安友康二等人发现，当其他一些免疫细胞首先感觉到某细胞出现异常时，这些免疫细胞便分泌出特殊物质。这些物质与杀伤性Ｔ细胞表面的 Notch2分子结合后，杀伤性Ｔ细胞就会对异常细胞展开攻击。老鼠实验证实，如果其他免疫细胞不能分泌上述特殊物质，或者该物质与Notch2分子不能 结合，它们的免疫功能就会减弱，这样的老鼠感染病毒后的死亡率也要高于正常老鼠。  

日本研究人员指出，如果能依靠药物控制杀伤性Ｔ细胞的出击时机，或许能帮助治疗癌症和某些病毒性传染病。（生物谷Bioon.com）

生物谷推荐原始出处：

Nature Immunology   Published online: 24 August 2008 | doi:10.1038/ni.1649

Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity

Yoichi Maekawa, Yoshiaki Minato, Chieko Ishifune, Takeshi Kurihara, Akiko Kitamura, Hidefumi Kojima, Hideo Yagita, Mamiko Sakata-Yanagimoto, Toshiki Saito, Ichiro Taniuchi, Shigeru Chiba, Saburo Sone & Koji Yasutomo

The acquisition of cytotoxic effector function by CD8⁺ T cells is crucial for the control of intracellular infection and tumor invasion. However, it remains unclear which signaling pathways are required for the differentiation of CD8⁺ cytotoxic T lymphocytes. We show here that Notch2-deficient T cells had impaired differentiation into cytotoxic T lymphocytes. In addition, dendritic cells with lower expression of the Notch ligand Delta-like 1 induced the differentiation of cytotoxic T lymphocytes less efficiently. We found that the intracellular domain of Notch2 interacted with a phosphorylated form of the transcription factor CREB1, and together these proteins bound the transcriptional coactivator p300 to form a complex on the promoter of the gene encoding granzyme B. Our results suggest that the highly regulated, dynamic control of T cell cytotoxicity depends on the integration of Notch2 and CREB1 signals.