IMMUNITY IN SYSTEMIC AND MUCOSAL VIRUS INFECTIONS

全身和粘膜病毒感染的免疫力

• 批准号: 6193249
• 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/6193249
• 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：（根据调查员的摘要进行了改编）：这是一个修订版 Liisa Selin博士的应用来研究系统性的交叉反应免疫 和粘膜病毒感染。许多病毒，例如爱泼斯坦巴尔病毒（EBV）， 巨细胞病毒（CMV）和流感（流感）病毒是T细胞的有效诱导剂 反应，导致高水平的CD8细胞毒性T产生 淋巴细胞（CTL）。这些病毒特异性T细胞介导的免疫反应可以 导致症状性疾病和发病机理，其严重程度可能有所不同 在个人之间显着。人类和小鼠病毒的研究 感染倾向于关注是否需要T细胞反应 清除特定病毒，以相对于病毒清除的动力学 T细胞反应，以及针对单个病毒的T细胞表位特异性。 但是，在本质上，宿主有多种感染的病史 和记忆T细胞池的大小和复杂性。我们在 鼠标系统表明，这些记忆T细胞群体不是休眠的T 细胞库，但实际上是连续骑自行车的，可以积极地 参与对新无关病毒的反应。调查员发现 小鼠中的急性病毒感染引起CTL的交叉反应与同种抗原 以及先前感染的病毒。异源病毒感染 刺激T细胞反应的T细胞反应，并且要么 对第二种无关病毒感染提供一些保护性免疫，否则 诱导严重的免疫病理学。第二次病毒感染之后 记忆CTL对第一种病毒的反应减少并定性改变。 研究人员提出了一个免疫网络，CD8 T细胞经常 与多个抗原和记忆T细胞池的交叉反应 由于对反应的免疫反应做出贡献，不断被修改 推定的无关病原体。这种类型的交叉反应性可能部分 解释由同一病毒引起的发病机理的个体变异，并解释 对这种交叉反应性的了解对于将来的疫苗可能很重要 发展。这项研究的目的是系统地检查 鼠标模型这些交叉反应性T细胞反应是否在 粘膜和全身病毒中的保护性免疫和免疫病变 感染。