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。 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 cytotoxicityYoichi 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. |
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