Characterizing the CD8 T cell response to RSV infection

表征 CD8 T 细胞对 RSV 感染的反应

• 批准号: 6993827
• 负责人: JONATHAN P CASTILLO
• 金额: $ 4.83万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6993827
• 关键词: T cell receptor; T lymphocyte; biological signal transduction; immune response; immunocytochemistry; immunoregulation; laboratory mouse; microorganism immunology; postdoctoral investigator; respiratory syncytial virus; virus infection mechanism; virus protein; western blottings

DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) is a significant respiratory pathogen that afflicts children and the elderly worldwide. The fact that individuals naturally infected with RSV are susceptible to re-infection insinuates that RSV has evolved a mechanism to modulate the host adaptive immune response. Our laboratory has previously demonstrated that following RSV challenge, a significant fraction of the virus-specific CD8+ T cells in the lungs exhibit impaired effector function (i.e. cytokine production and ex vivo cytolytic activity). This defective effector response is localized primarily to the CD8+ T cells accumulating in the lung compartment; is associated with a rapid decline in the frequency of peripheral CD8+ memory T cells; and is attributed to RSV infection. This proposal will address the mechanisms contributing to the immune dysregulation of CD8+ effector T cell activity by (1) assessing the molecular basis for the defect in effector function exhibited by virus-specific CD8+ T cells in the lung; and (2) identifying the RSV gene product that induces the partial inhibition of virus-specific CD8+ effector activity in the lung. The results from this study will provide a better understanding of the relationship between RSV and CD8+ T cell immunity.

描述（由申请人提供）：呼吸道合胞病毒（RSV）是一种重要的呼吸道病原体，困扰着全世界的儿童和老年人。事实上，自然感染 RSV 的个体很容易再次感染，这表明 RSV 已经进化出一种调节宿主适应性免疫反应的机制。我们的实验室此前已证明，RSV 攻击后，肺部中很大一部分病毒特异性 CD8+ T 细胞表现出效应功能受损（即细胞因子产生和离体细胞溶解活性）。这种有缺陷的效应反应主要集中在肺室中积累的 CD8+ T 细胞；与外周 CD8+ 记忆 T 细胞频率的快速下降有关；并归因于 RSV 感染。该提案将通过以下方式解决导致 CD8+ 效应 T 细胞活性免疫失调的机制：(1) 评估肺部病毒特异性 CD8+ T 细胞表现出的效应功能缺陷的分子基础； (2)鉴定诱导肺部病毒特异性CD8+效应子活性部分抑制的RSV基因产物。这项研究的结果将有助于更好地理解 RSV 和 CD8+ T 细胞免疫之间的关系。