Visualizing the viral burden: Phenotypic and functional alterations of T cells and APCs during persistent infection
Visualizing the viral burden: Phenotypic and functional alterations of T cells and APCs during persistent infection
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DOI：
10.4049/jimmunol.172.10.6239
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发表时间：
2004-05-15
影响因子：
4.4
通讯作者：
Oldstone, MBA
中科院分区：
文献类型：
--
作者：
Homann, D;McGavern, DB;Oldstone, MBA
持续的病毒感染继续构成重大的公共卫生问题。未能实现病毒控制使免疫系统面临慢性病毒负荷，其可能涉及免疫细胞本身并直接损害效应淋巴细胞和APC的功能。在这项研究中，我们使用的淋巴细胞脉络丛脑膜炎病毒系统的持续病毒感染的自然鼠宿主和使用分析技术直接离体可视化的病毒感染的免疫细胞。我们报告说，几乎所有的免疫系统细胞可以被感染，但病毒负荷的分布是有区别地分配给淋巴细胞和APC亚群的定义表型。重要的是，血液中发现的免疫细胞感染谱广泛代表大多数器官中的细胞感染模式，并且与Ab或补体的存在无关。通过病毒感染和未感染的细胞亚群的直接比较，我们证明，淋巴细胞性脉络丛脑膜炎病毒感染的T细胞显示优先激活，歪斜的细胞因子谱，并增加凋亡。相反，APC的活化增加是普遍的，并且与病毒Ag的存在无关。我们的数据表明，免疫细胞感染的特定模式与不同形式的免疫刺激和免疫抑制改变相关，这可能为了解与感染性疾病相关的自身免疫过程提供见解，并为旨在恢复完全免疫的治疗干预提供线索。
Persistent viral infections continue to present major public health problems. Failure to achieve virus control confronts the immune system with a chronic viral burden that may involve immune cells themselves and directly compromise the functionality of effector lymphocytes and APCs. In this study we use the lymphocytic choriomeningitis virus system for persistent viral infection of its natural murine host and use analytical techniques for direct ex vivo visualization of virus-infected immune cells. We report that virtually all cells of the immune system can be infected, but the distribution of the viral burden is differentially allocated to lymphocyte and APC subsets of defined phenotypes. Importantly, the profile of immune cell infection found in the blood is broadly representative for the pattern of cellular infection in most organs and is independent of the presence of Abs or complement. By direct comparison of virus-infected and uninfected cell subsets, we demonstrate that lymphocytic choriomeningitis virus-infected T cells show preferential activation, skewed cytokine profiles, and increased apoptosis. In contrast, increased activation of APCs is generalized and independent of the presence of viral Ag. Our data indicate that specific patterns of immune cell infection are associated with distinct forms of immunostimulatory and immunosuppressive alterations that may provide insights into autoimmune processes associated with infectious disease and offer clues for therapeutic interventions aimed at restoration of complete immunity.