On the Role of CD8(+) T Cells in Determining Recovery Time from Influenza Virus Infection.
On the Role of CD8(+) T Cells in Determining Recovery Time from Influenza Virus Infection.
复制标题
DOI：
10.3389/fimmu.2016.00611
复制
发表时间：
2016
影响因子：
7.3
通讯作者：
McCaw JM
中科院分区：
文献类型：
--
作者：
Cao P;Wang Z;Yan AW;McVernon J;Xu J;Heffernan JM;Kedzierska K;McCaw JM
无数的实验已经确定了CD8+ T细胞应答机制在确定从甲型流感病毒感染中恢复中的重要作用。流感感染的动物模型进一步暗示了定义病毒感染的动态特征的免疫应答的多个要素。到目前为止，流感病毒模型，虽然捕捉自然感染史的特定方面，已经无法再现观察到的病毒动力学行为的全部范围内在一个单一的连贯的框架。在这里，我们介绍了一个数学模型的流感病毒动力学纳入先天，体液和细胞免疫成分，并探讨其性质，特别强调细胞免疫的作用。针对一系列小鼠数据进行校准，我们的模型能够从大量实验中重现观察到的病毒动力学。重要的是，该模型预测了效应CD8+ T细胞水平与恢复时间之间的稳健指数关系，从而随着效应CD8+ T细胞水平的增加，恢复时间迅速降低至固定的最小恢复时间。我们在最近的甲型H7N9流感住院患者的临床数据中发现了这种关系的支持。指数关系意味着具有较低水平的初始CD8+ T细胞的人可以从诱导由免疫记忆产生的额外效应CD8+ T细胞中获得显著更多的益处，免疫记忆本身通过先前的病毒感染或基于T细胞的疫苗建立。
Myriad experiments have identified an important role for CD8+ T cell response mechanisms in determining recovery from influenza A virus infection. Animal models of influenza infection further implicate multiple elements of the immune response in defining the dynamical characteristics of viral infection. To date, influenza virus models, while capturing particular aspects of the natural infection history, have been unable to reproduce the full gamut of observed viral kinetic behavior in a single coherent framework. Here, we introduce a mathematical model of influenza viral dynamics incorporating innate, humoral, and cellular immune components and explore its properties with a particular emphasis on the role of cellular immunity. Calibrated against a range of murine data, our model is capable of recapitulating observed viral kinetics from a multitude of experiments. Importantly, the model predicts a robust exponential relationship between the level of effector CD8+ T cells and recovery time, whereby recovery time rapidly decreases to a fixed minimum recovery time with an increasing level of effector CD8+ T cells. We find support for this relationship in recent clinical data from influenza A (H7N9) hospitalized patients. The exponential relationship implies that people with a lower level of naive CD8+ T cells may receive significantly more benefit from induction of additional effector CD8+ T cells arising from immunological memory, itself established through either previous viral infection or T cell-based vaccines.
登录
查看更多内容
影响因子：
3.7
作者：
Dobrovolny HM;Reddy MB;Kamal MA;Rayner CR;Beauchemin CA
通讯作者：
Beauchemin CA
在B淋巴细胞缺陷小鼠中对致命流感病毒感染的抗性和恢复。
影响因子：
15.3
作者：
Graham, M B;Braciale, T J
通讯作者：
Braciale, T J
影响因子：
2
作者：
Chao, DL;Davenport, MP;Perelson, AS
通讯作者：
Perelson, AS
影响因子：
4.4
作者：
Fang, M;Sigal, LJ
通讯作者：
Sigal, LJ
DOI：
10.1073/pnas.0705905104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Cicin-Sain, Luka;Messaoudi, Ilhem;Nikolich-Zugich, Janko
通讯作者：
Nikolich-Zugich, Janko