Novel function of perforin in negatively regulating CD4^+ T cell activation by affecting calcium signaling

查看全文 作　　者：Enguang [1]Bi;Chunjian [1]Huang;Yu [1]Hu;Xiaodong [1]Wu;Weiwen [1]Deng;Guomei [1]Lin;Zhiduo [1]Liu;Lin [1]Tian;Shuhui [2]Sun;Kairui [1]Mao;Jia [1]Zou;Yuhan [1]Zheng;Bing [1,3]Sun

机构地区：[1]Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China;[2]Fudan University School of Medicine, Shanghai 200032, China;[3]Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025, China

出　　处：《Cell Research》索引2009年第19卷第7期,共12页

基　　金：Acknowledgments We thank Drs Hua Gu (Columbia University, USA), Weiguo Zhang (Duke University Medical Center, USA), and Youhai H Chen (University of Pennsylvania, USA) for reviewing the manuscript and for suggestions, and Dr Ilia Voskoboinik (Peter MacCallum Cancer Centre, Australia) for providing the mouse perforin cDNA in pKS(+) Bluescript. Ragl^-/- mice were gifts from Xiaolong Liu (Shanghai Institutes for Biological Sciences, China). This work was supported by grants from the National Natural Science Foundation of China (30325018, 30530700, 30623003, and 30421005) and CAS project (KSCX1-YW-R-43), grants from the National Key Project 973 (2006CB504300 and 2007CB512404), grants from the Technology Commission of Shanghai Municipality (04DZ14902, 04DZ19108, 06DZ22032, 04DZ19112, 07XD14033, and 07DZ22916), 863 key project (2006AA02A247), and a grant from the E-institutes of Shanghai Universities Immunology Division. 摘　　要：Perforin 是主要从事调停的形成毛孔的蛋白质目标 T 房间死亡并且被细胞毒素的 T 淋巴细胞(CTL ) 和自然漂亮房间采用。然而,它是否也在常规 CD4+ T 房间功能起一个作用,仍然保持不清楚。这里,我们报导那在 perforin 缺乏(PKO ) 老鼠, CD4+ T 房间是响应 T 的 hyperproliferative 房间受体(TCR ) 刺激。hyperproliferation 的这个特征被改进在房间分割并且在 IL-2 分泌物伴随。看起来, perforin 缺乏不在胸腺怒气和淋巴节点影响 T 房间开发。在 vivo, perforin 缺乏导致增加的抗原特定的 T 房间增长和抗体生产。而且, PKO 老鼠更产生试验性的自体免疫的眼色素层炎。探讨分子的机制,我们发现在 TCR 刺激以后,从 PKO 老鼠的 CD4+ T 房间显示增加的细胞内部的钙流动并且随后提高抄写因素 NFAT1 的激活。我们的结果显示 perforin 在由影响 TCR 依赖的 Ca2+ 发信号调整 CD4+ T 房间激活和有免疫力的反应起一个否定作用。 关键词：T细胞活化 CD4 钙信号穿孔细胞毒性T淋巴细胞 T细胞受体自然杀伤细胞维和行动

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Novel function of perforin in negatively regulating CD4^+ T cell activation by affecting calcium signaling

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