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白细胞介素-2受体信号在急性和慢性病毒感染中对CD8 + T细胞反应的不同作用。

Differential role of IL-2R signaling for CD8+ T cell responses in acute and chronic viral infections.

作者信息

Bachmann Martin F, Wolint Petra, Walton Senta, Schwarz Katrin, Oxenius Annette

机构信息

Cytos Biotechnology AG, Zürich-Schlieren, Switzerland.

出版信息

Eur J Immunol. 2007 Jun;37(6):1502-12. doi: 10.1002/eji.200637023.

DOI:10.1002/eji.200637023
PMID:17492805
Abstract

IL-2 is a cytokine with multiple and even divergent functions; it has been described as a key cytokine for in vitro T cell proliferation but is also essential for down-regulating T cell responses by inducing activation-induced cell death as well as regulatory T cells. The in vivo analysis of IL-2 function in regulating specific T cell responses has been hampered by the fact that mice deficient in IL-2 or its receptors develop lymphoproliferative diseases and/or autoimmunity. Here we generated chimeric mice harboring both IL-2R-competent and IL-2R-deficient T cells and assessed CD8+ T cell induction, function and maintenance after acute or persistent viral infections. Induction and maintenance of CD8+ T cells were relatively independent of IL-2R signaling during acute/resolved viral infection. In marked contrast, IL-2 was crucial for secondary expansion of memory CD8+ T cells and for the maintenance of virus-specific CD8+ T cells during persistent viral infections. Thus, depending on the chronicity of antigen exposure, IL-2R signaling is either essential or largely dispensable for induction and maintenance of virus-specific CD8+ T cell responses.

摘要

白细胞介素-2(IL-2)是一种具有多种甚至相互矛盾功能的细胞因子;它被描述为体外T细胞增殖的关键细胞因子,但通过诱导活化诱导的细胞死亡以及调节性T细胞来下调T细胞反应也至关重要。由于缺乏IL-2或其受体的小鼠会发生淋巴细胞增殖性疾病和/或自身免疫,因此对IL-2在调节特定T细胞反应中的功能进行体内分析受到了阻碍。在这里,我们构建了同时含有具有IL-2受体功能和缺乏IL-2受体的T细胞的嵌合小鼠,并评估了急性或持续性病毒感染后CD8 + T细胞的诱导、功能和维持情况。在急性/已消退的病毒感染期间,CD8 + T细胞的诱导和维持相对独立于IL-2受体信号传导。与之形成鲜明对比的是,在持续性病毒感染期间,IL-2对于记忆性CD8 + T细胞的二次扩增以及病毒特异性CD8 + T细胞的维持至关重要。因此,根据抗原暴露的慢性程度,IL-2受体信号传导对于病毒特异性CD8 + T细胞反应的诱导和维持要么必不可少,要么在很大程度上是可有可无的。

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