Role of T Cells in Virus Control and Disease after Infection with Pneumonia Virus of Mice
Role of T Cells in Virus Control and Disease after Infection with Pneumonia Virus of Mice
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DOI：
10.1128/jvi.00375-08
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发表时间：
2008-12-01
影响因子：
5.4
通讯作者：
Ehl, Stephan
中科院分区：
文献类型：
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作者：
Frey, Stefanie;Krempl, Christine D.;Ehl, Stephan
小鼠感染小鼠肺炎病毒（PVM）被用作一种天然宿主实验模型，用于研究与其密切相关的人类呼吸道合胞病毒感染的发病机制。我们分析了T细胞在PVM感染后对病毒控制和病理的作用。C57BL/6小鼠感染PVM 15株亚致死剂量后，肺部细胞毒性T淋巴细胞增加了100倍，其中20%对PVM具有特异性。T细胞缺陷型小鼠无法清除PVM，并在没有对照小鼠感染后出现的肺炎临床或组织病理学症状的情况下成为病毒携带者。T细胞数量有限的小鼠在没有体重减轻的情况下无法实现病毒控制，这表明T细胞介导的病毒控制与免疫病理学密切相关。CD4和CD8 T细胞都独立地对病毒清除和疾病产生作用。在缺乏穿孔素、γ干扰素或肿瘤坏死因子α的情况下，病毒控制和疾病情况相似。有趣的是，致死性高剂量PVM感染后的疾病和死亡率与T细胞无关。这些数据说明了T细胞在控制PVM感染中的关键作用，并证明了T细胞依赖和非依赖途径都以病毒剂量依赖的方式导致疾病。
Infection of mice with pneumonia virus of mice (PVM) is used as a natural host experimental model for studying the pathogenesis of infection with the closely related human respiratory syncytial virus. We analyzed the contribution of T cells to virus control and pathology after PVM infection. Control of a sublethal infection with PVM strain 15 in C57BL/6 mice was accompanied by a 100-fold increase in pulmonary cytotoxic T lymphocytes, 20% of which were specific for PVM. T-cell-deficient mice failed to eliminate PVM and became virus carriers in the absence of the clinical or histopathological signs of pneumonia that occurred after infection of control mice. Mice with limited T-cell numbers did not achieve virus control without weight loss, indicating that T-cell-mediated virus control was closely linked to immunopathology. Both CD4 and CD8 T cells independently contributed to virus elimination and disease. Virus control and disease were similar in the absence of perforin, gamma interferon, or tumor necrosis factor alpha. Interestingly, disease and mortality after lethal high-dose PVM infection were independent of T cells. These data illustrate a key role for T cells in control of PVM infection and demonstrate that both T-cell-dependent and -independent pathways contribute to disease in a viral dose-dependent fashion.