T CELL IMMUNITY TO RESPIRATORY VIRUS INFECTIONS

T 细胞对呼吸道病毒感染的免疫力

• 批准号: 6209815
• 负责人: ROBERT J HOGAN
• 金额: $ 3.24万
• 依托单位: TRUDEAU INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6209815
• 关键词: Orthomyxoviridae; cell population study; cytotoxic T lymphocyte; immunologic memory; laboratory mouse; parainfluenza virus type 1; respiratory infections

Respiratory virus infections are a major cause of morbidity and mortality worldwide. CD8+ cytotoxic T lymphocytes (CTL) have been shown to play a central role in controlling primary infection and represent an important target for improving current vaccines designed to emphasize cellular responses against this class of viruses. In the current proposal, we take advantage of two well-established models of respiratory virus infections (Sendai virus and influenza virus) to investigate the recall of memory CD8+ T cells. Preliminary data show that substantial numbers of antigen-specific T cells can be found not only in the spleen, but also in the lung tissue and lavage following both Sendai virus and influenza virus infection. Interestingly, memory CD8+ T cells in the lung differ from those observed in the spleen in terms of phenotype and frequency among CD8+ T cells. The underlying hypothesis of the proposal is that memory CD8+ T cells in the lung make a substantial contribution to the rapid recall response during secondary infection. This hypothesis will be tested by (I) characterizing antigen-specific CD8+ memory T cells that persist in the lungs following recovery from respiratory virus infection, and (II) determining the relative contributions of distinct populations of memory cells to the recall response.

呼吸道病毒感染是全世界发病和死亡的主要原因。 CD8+ 细胞毒性 T 淋巴细胞 (CTL) 已被证明在控制原发性感染中发挥着核心作用，并且是改进当前旨在强调针对此类病毒的细胞反应的疫苗的重要目标。 在当前的提案中，我们利用两种成熟的呼吸道病毒感染模型（仙台病毒和流感病毒）来研究记忆 CD8+ T 细胞的记忆。 初步数据显示，仙台病毒和流感病毒感染后，不仅在脾脏中，而且在肺组织和灌洗液中都可以发现大量抗原特异性 T 细胞。 有趣的是，肺中的记忆 CD8+ T 细胞与脾脏中观察到的 CD8+ T 细胞的表型和频率不同。该提案的基本假设是，肺部的记忆 CD8+ T 细胞对继发感染期间的快速记忆反应做出了重大贡献。 这一假设将通过以下方式进行检验：(I) 表征从呼吸道病毒感染恢复后持续存在于肺部的抗原特异性 CD8+ 记忆 T 细胞，以及 (II) 确定不同记忆细胞群体对回忆反应的相对贡献。