T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice
T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice
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DOI：
10.1128/jvi.01049-10
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发表时间：
2010-09-15
影响因子：
5.4
通讯作者：
Perlman, Stanley
中科院分区：
文献类型：
--
作者：
Zhao, Jincun;Zhao, Jingxian;Perlman, Stanley
先天免疫反应失调和细胞因子/趋化因子表达旺盛被认为是冠状病毒（SARS-CoV）引起的严重急性呼吸道综合征（SARS）发病机制的关键因素。然而，我们最近发现，低效的免疫激活和病毒特异性T细胞反应较差是SARS-CoV感染小鼠严重疾病的基础。在这里，我们扩展了这些结果，以表明病毒特异性T细胞，在没有激活先天免疫反应的情况下，足以显着提高生存率和减少临床疾病。我们证明了T细胞负责病毒清除，因为将SARS-CoV免疫脾细胞或体外产生的T细胞静脉过继转移到SCID或BALB/c小鼠中可提高存活率并降低肺中的病毒滴度。通过用SARS-CoV肽脉冲树突状细胞免疫增强病毒特异性CD 8 T细胞的数量也导致了强大的T细胞应答、更早的病毒清除和增加的存活。这些研究首次表明，T细胞在SARS-CoV清除中起着至关重要的作用，并且次优的T细胞应答有助于在SARS中观察到的病理变化。它们还为SARS疫苗的设计提供了一种新的方法。
A dysregulated innate immune response and exuberant cytokine/chemokine expression are believed to be critical factors in the pathogenesis of severe acute respiratory syndrome (SARS), caused by a coronavirus (SARS-CoV). However, we recently showed that inefficient immune activation and a poor virus-specific T cell response underlie severe disease in SARS-CoV-infected mice. Here, we extend these results to show that virus-specific T cells, in the absence of activation of the innate immune response, were sufficient to significantly enhance survival and diminish clinical disease. We demonstrated that T cells are responsible for virus clearance, as intravenous adoptive transfer of SARS-CoV-immune splenocytes or in vitro-generated T cells to SCID or BALB/c mice enhanced survival and reduced virus titers in the lung. Enhancement of the number of virus-specific CD8 T cells by immunization with SARS-CoV peptide-pulsed dendritic cells also resulted in a robust T cell response, earlier virus clearance, and increased survival. These studies are the first to show that T cells play a crucial role in SARS-CoV clearance and that a suboptimal T cell response contributes to the pathological changes observed in SARS. They also provide a new approach to SARS vaccine design.