Timing of CD8 T cell effector responses in viral infections.
Timing of CD8 T cell effector responses in viral infections.
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DOI：
10.1098/rsos.150661
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发表时间：
2016-02
影响因子：
3.5
通讯作者：
Wodarz D
中科院分区：
文献类型：
--
作者：
Stipp SR;Iniguez A;Wan F;Wodarz D
CD8 T细胞或细胞毒性T淋巴细胞（CTL）应答是免疫系统对抗病毒感染的重要分支。抗病毒CTL应答的动力学已经在实验和数学模型方面进行了一些详细的表征。一个有趣的实验观察涉及CTL应答的时机。最近的一项研究报道，在小鼠的肺炎病毒中，效应CTL倾向于仅在达到最大病毒载量后到达肺，这一观察结果起初似乎是违反直觉的，因为预防病理需要更早的CTL介导的活性。CTL介导的效应子活性的延迟也被引用作为与基于CTL的疫苗相关的困难的可能解释。本文使用数学模型表明，在特定的参数制度，延迟的CTL效应活性可以是有利的宿主在这个意义上，它可以增加病毒清除的机会。然而，CTL清除感染的能力增加，预计将以急性病理学为代价，引起权衡，这是根据进化过程进行讨论。这项工作为理解所描述的实验观察提供了理论基础。
CD8 T cell or cytotoxic T lymphocyte (CTL) responses are an important branch of the immune system in the fight against viral infections. The dynamics of anti-viral CTL responses have been characterized in some detail, both experimentally and with mathematical models. An interesting experimental observation concerns the timing of CTL responses. A recent study reported that in pneumonia virus of mice the effector CTL tended to arrive in the lung only after maximal virus loads had been achieved, an observation that seems at first counterintuitive because prevention of pathology would require earlier CTL-mediated activity. A delay in CTL-mediated effector activity has also been quoted as a possible explanation for the difficulties associated with CTL-based vaccines. This paper uses mathematical models to show that in specific parameter regimes, delayed CTL effector activity can be advantageous for the host in the sense that it can increase the chances of virus clearance. The increased ability of the CTL to clear the infection, however, is predicted to come at the cost of acute pathology, giving rise to a trade-off, which is discussed in the light of evolutionary processes. This work provides a theoretical basis for understanding the described experimental observations.