Disruption of Akt kinase activation is important for immunosuppression induced by measles virus

Disruption of Akt kinase activation is important for immunosuppression induced by measles virus
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DOI:
10.1038/89106
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发表时间:
2001-06-01
期刊:
影响因子:
82.9
通讯作者:
Schneider-Schaulies, S
Schneider-Schaulies, S
中科院分区:
医学1区
文献类型:
--
作者:
Avota, E;Avots, A;Schneider-Schaulies, S

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麻疹病毒(MV)融合和血凝素糖蛋白诱导的表面接触介导的信号传导是必要的,足以在体外和体内诱导T细胞无反应性。为了确定所涉及的细胞内途径,我们分析了原代人T细胞和Kit-225细胞中的白细胞介素(IL)-2R信号传导。与IL-2依赖的JAK/STAT通路活化不同,在体外和体内MV接触后Akt激酶的活化受损。MV干扰Akt活化对于免疫抑制是重要的,因为催化活性Akt的表达阻止了MV糖蛋白的负信号传导。因此,我们在这里表明,MV利用一种新的策略来干扰免疫抑制过程中的T细胞活化。
Surface-contact-mediated signaling induced by the measles virus (MV) fusion and hemagglutinin glycoproteins is necessary and sufficient to induce T-cell unresponsiveness in vitro and in vivo. To define the intracellular pathways involved, we analyzed interleukin (IL)-2R signaling in primary human T cells and in Kit-225 cells. Unlike IL-2-dependent activation of JAK/STAT pathways, activation of Akt kinase was impaired after MV contact both in vitro and in vivo. MV interference with Akt activation was important for immunosuppression, as expression of a catalytically active Akt prevented negative signaling by the MV glycoproteins. Thus, we show here that MV exploits a novel strategy to interfere with T-cell activation during immunosuppression.