The role of mTOR in memory CD8 T-cell differentiation.
The role of mTOR in memory CD8 T-cell differentiation.
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DOI：
10.1111/j.0105-2896.2010.00898.x
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发表时间：
2010-05
影响因子：
8.7
通讯作者：
Ahmed R
中科院分区：
文献类型：
--
作者：
Araki K;Youngblood B;Ahmed R
哺乳动物雷帕霉素靶蛋白（mTOR）是一种调节细胞生长和代谢的细胞内激酶。其特异性抑制剂雷帕霉素目前作为免疫抑制药物用于移植受者，以防止同种异体移植排斥反应。研究表明，雷帕霉素的免疫抑制作用机制复杂多样。据报道，该药物可抑制T细胞增殖，诱导无反应性，调节T细胞运输，促进调节性T细胞，还可防止树突状细胞成熟以及I型IFN的产生。然而，其他几项研究矛盾地证明了雷帕霉素通过改善抗原呈递和调节巨噬细胞和骨髓树突状细胞的细胞因子产生来产生免疫刺激作用。最近，已经表明雷帕霉素也对记忆性CD8+ T细胞分化表现出免疫刺激作用。该药物改善了由病毒感染和疫苗接种诱导的记忆CD8+ T细胞的数量和质量，表明mTOR是记忆CD8+ T细胞分化的主要调节因子。这些发现对新型疫苗方案的开发具有影响。本文综述了mTOR在记忆性CD8+ T细胞分化中的作用，并比较了雷帕霉素在CD8+ T细胞、CD4+ T细胞和树突状细胞中的作用。我们还讨论了这些发现在临床环境中的潜在应用。
The mammalian target of rapamycin (mTOR) is an intracellular kinase that regulates cell growth and metabolism. Its specific inhibitor rapamycin is currently used in transplant recipients as an immunosuppressive drug to prevent allograft rejection. Studies have shown complex and diverse mechanisms for the immunosuppressive effects of rapamycin. The drug has been reported to inhibit T-cell proliferation, induce anergy, modulate T-cell trafficking, promote regulatory T cells, and also prevent maturation of dendritic cells as well as production of type I IFN production. However, several other studies have paradoxically demonstrated immunostimulatory effects of rapamycin by improving antigen presentation and regulating cytokine production from macrophages and myeloid dendritic cells. Recently, it has been shown that rapamycin also exhibits immunostimulatory effects on memory CD8+ T-cell differentiation. The drug improved both quantity and quality of memory CD8+ T cells induced by viral infection and vaccination, showing that mTOR is a major regulator of memory CD8+ T-cell differentiation. These discoveries have implications for the development of novel vaccine regimens. Here we review the role of mTOR in memory CD8+ T-cell differentiation and compare the effect of rapamycin between CD8+ T cells, CD4+ T cells, and dendritic cells. Also we discuss potential application of these findings in a clinical setting.
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DOI：
10.1084/jem.20001021
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blattman JN;Antia R;Sourdive DJ;Wang X;Kaech SM;Murali-Krishna K;Altman JD;Ahmed R
通讯作者：
Ahmed R
影响因子：
20.3
作者：
Hackstein, H;Taner, T;Thomson, AW
通讯作者：
Thomson, AW
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
158.5
作者：
Ekberg, Henrik;Tedesco-Silva, Helio;Halloran, Philip F.
通讯作者：
Halloran, Philip F.
影响因子：
8.8
作者：
Gao, W.;Lu, Y.;Strom, T. B.
通讯作者：
Strom, T. B.