IMMUNITY IN SYSTEMIC AND MUCOSAL VIRUS INFECTIONS

全身和粘膜病毒感染的免疫力

• 批准号: 6374380
• 负责人: Liisa Kaarina Selin
• 金额: $ 27.3万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-15 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6374380
• 关键词: Betaherpesvirinae; Orthomyxoviridae; cellular immunity; cross immunity; cytotoxic T lymphocyte; immunologic memory; interleukin 10; laboratory mouse; leukocyte activation /transformation; lymphocytic choriomeningitis virus; mucosal immunity; vaccinia virus

DESCRIPTION: (Adapted from the Investigator's abstract): This is a revised application from Dr. Liisa Selin to study cross-reactive immunity to systemic and mucosal viral infections. Many viruses, such as Epstein Barr virus (EBV), cytomegalovirus (CMV), and influenza (FLU) virus, are potent inducers of T cell responses, resulting in the generation of high levels of CD8 cytotoxic T lymphocytes (CTL). These virus-specific T cell mediated immune responses can lead to symptomatic disease and pathogenesis, the severity of which can vary significantly between individuals. Studies of both human and mouse viral infections have tended to focus on whether a T cell response is required to clear a particular virus, on the kinetics of virus clearance in relation to the T cell response, and on T cell epitope specificity for individual viruses. However, in nature the host has a history of multiple infections in sequence and memory T cell pools of significant size and complexity. Our work in the mouse system has shown that these memory T cell populations are not dormant T cell reservoirs, but are, in fact continuously cycling and can actively participate in responses to new unrelated viruses. The investigator has found that acute virus infections in mice elicit CTL cross-reactive with alloantigens and with viruses from previous infections. A heterologous viral infection stimulates T cell responses that may prime an immune response and either provide some protective immunity to a second unrelated viral infection or else induce severe immunopathology. Subsequent to a second viral infection, the memory CTL response to the first virus is diminished and qualitatively altered. The investigator proposes an immunological network whereby CD8 T cells often cross-react with more than one antigen, and where memory T cell pools are continually being modified as they contribute to the immune responses against putatively unrelated pathogens. This type of cross-reactivity may partially explain the individual variation in pathogenesis caused by the same virus, and knowledge of such cross-reactivity may be important for future vaccine development. The purpose of this study is to systematically examine in the mouse model whether these cross-reactive T cell responses play a role in protective immunity and immunopathogenesis in both mucosal and systemic virus infections.

描述：（改编自研究者摘要）：这是一份修订版 Liisa Selin博士申请研究全身性交叉反应免疫 和粘膜病毒感染。许多病毒，如爱泼斯坦巴尔病毒（EBV）， 巨细胞病毒（CMV）和流感病毒（FLU）是T细胞的有效诱导剂， 反应，导致产生高水平的CD8细胞毒性T细胞 淋巴细胞（CTL）。这些病毒特异性T细胞介导的免疫应答可以 导致症状性疾病和发病机制，其严重程度可能不同 个体之间的重要性。人类和小鼠病毒的研究 感染往往集中在是否需要T细胞反应， 清除特定病毒，对病毒清除动力学的影响 T细胞应答和对单个病毒的T细胞表位特异性。 然而，在自然界中，宿主有顺序的多次感染史 以及具有显著大小和复杂性的记忆T细胞池。我们搞好 小鼠系统已经表明，这些记忆T细胞群不是休眠T细胞， 细胞库，但事实上，不断循环，并可以积极 参与对新的不相关病毒的反应。调查员发现 小鼠急性病毒感染引起CTL与同种异体抗原交叉反应， 以及之前感染的病毒。一种异源病毒感染 刺激T细胞反应，可能引发免疫反应， 对第二次不相关的病毒感染提供一定的保护性免疫力， 导致严重免疫病理学。在第二次病毒感染后， 对第一种病毒的记忆性CTL应答减弱并发生质的改变。 研究人员提出了一种免疫网络，其中CD8 T细胞通常 与一种以上的抗原交叉反应，并且记忆T细胞池 不断被修饰，因为它们有助于免疫反应， 不相关的病原体。这种类型的交叉反应可能部分 解释由同一病毒引起的发病机制的个体差异，以及 了解这种交叉反应性对于未来疫苗可能是重要的 发展本研究的目的是系统地考察 小鼠模型是否这些交叉反应性T细胞反应发挥作用， 粘膜和全身病毒的保护性免疫和免疫发病机制 感染.