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：（改编自研究者的摘要）：这是修订版 Liisa Selin 博士申请研究系统性交叉反应免疫 和粘膜病毒感染。许多病毒，例如 Epstein Barr 病毒 (EBV)， 巨细胞病毒 (CMV) 和流感 (FLU) 病毒是 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 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制，其严重程度可能有所不同 个体之间显着。人类和小鼠病毒的研究 感染往往集中于是否需要 T 细胞反应 清除特定病毒，根据病毒清除动力学与 T 细胞反应，以及针对个体病毒的 T 细胞表位特异性。 然而，本质上宿主有多次依次感染的历史 以及具有显着大小和复杂性的记忆 T 细胞池。我们的工作在 小鼠系统表明这些记忆 T 细胞群并不是休眠 T 细胞 细胞储存库，但实际上是不断循环的，并且可以主动 参与对新的不相关病毒的反应。调查人员发现 小鼠急性病毒感染引起 CTL 与同种异体抗原发生交叉反应 以及以前感染的病毒。异源病毒感染 刺激 T 细胞反应，从而引发免疫反应，或者 对第二种不相关的病毒感染提供一定的保护性免疫力，或者 诱发严重的免疫病理学。第二次病毒感染后， 记忆CTL对第一种病毒的反应减弱并发生质变。 研究人员提出了一个免疫网络，其中 CD8 T 细胞经常 与不止一种抗原发生交叉反应，记忆 T 细胞池所在的位置 由于它们有助于抵抗病毒的免疫反应，因此不断被修改 假定不相关的病原体。这种类型的交叉反应可能部分 解释同一病毒引起的发病机制的个体差异，以及 了解这种交叉反应可能对未来的疫苗很重要 发展。本研究的目的是系统地考察 小鼠模型中这些交叉反应性 T 细胞反应是否在 粘膜和全身病毒的保护性免疫和免疫发病机制 感染。