Activation and inactivation of antiviral CD8 T cell responses during murine pneumovirus infection
Activation and inactivation of antiviral CD8 T cell responses during murine pneumovirus infection
复制标题
DOI：
10.4049/jimmunol.175.10.6597
复制
发表时间：
2005-11-15
影响因子：
4.4
通讯作者：
van der Most, RG
中科院分区：
文献类型：
--
作者：
Claassen, EAW;van der Kant, PAA;van der Most, RG
小鼠肺炎病毒（PVM）是小鼠的天然病原体，并且已经被提议作为用于在其天然宿主中复制肺炎病毒的易处理的模型，其模拟人类感染人呼吸道合胞病毒（RSV）。与RSV在小鼠中观察到的情况相比，PVM感染在小鼠中的病毒产生方面是高产的。由于RSV抑制感染小鼠肺部的CD 8 T细胞效应功能，我们研究了PVM诱导的CD 8 T细胞应答的性质，以研究天然病毒宿主环境中肺炎病毒诱导的T细胞应答。PVM感染与大量活化的CD 8 T细胞流入肺部有关。在鉴定三种PVM特异性CD 8 T细胞表位后，计数肺CD 8 T细胞应答。对三个表位特异的分泌亮氨酸的CD 8 T细胞的组合频率远小于活化的CD 8 T细胞的总数。此外，通过MHC I类五聚体染色和体外刺激随后细胞内IFN-γ和TNF-α染色对针对这些表位之一（来自磷蛋白的残基261-270）的CD 8 T细胞应答进行定量，表明大多数对P-261表位特异的肺CD 8在细胞因子产生方面是缺陷的。这种缺陷型在感染后96天仍保留，与人RSV感染小鼠肺中的情况相似。数据表明PVM抑制肺中的T细胞效应功能。
Pneumonia virus of mice (PVM) is a natural pathogen of mice and has been proposed as a tractable model for the replication of a pneumovirus in its natural host, which mimics human infection with human respiratory syncytial virus (RSV). PVM infection in mice is highly productive in terms of virus production compared with the situation seen with RSV in mice. Because RSV suppresses CD8 T cell effector function in the lungs of infected mice, we have investigated the nature of PVM-induced CD8 T cell responses to study pneumovirus-induced T cell responses in a natural virus-host setting. PVM infection was associated with a massive influx of activated CD8 T cells into the lungs. After identification of three PVM-specific CD8 T cell epitopes, pulmonary CD8 T cell responses were enumerated. The combined frequency of cytokine-secreting CD8 T cells specific for the three epitopes was much smaller than the total number of activated CD8 T cells. Furthermore, quantitation of the CD8 T cell response against one of these epitopes (residues 261-270 from the phosphoprotein) by MHC class I pentamer staining and by in vitro stimulation followed by intracellular IFN-gamma and TNF-alpha staining indicated that the majority of pulmonary CD8 specific for the P-261 epitope were deficient in cytokine production. This deficient phenotype was retained up to 96 days postinfection, similar to the situation in the lungs of human RSV-infected mice. The data suggest that PVM suppresses T cell effector functions in the lungs.