T CELL IMMUNITY TO RESPIRATORY VIRUS INFECTIONS

呼吸道病毒感染是全世界发病率和死亡率的一个主要原因。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核心作用，并且是改进当前旨在强调针对这类病毒的细胞反应的疫苗的重要靶标。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）来研究记忆性CD8+ T细胞的召回。初步数据显示，大量抗原特异性T细胞不仅存在于脾脏中，也存在于仙台病毒和流感病毒感染后的肺组织和灌洗液中。有趣的是，就CD8+ T细胞的表型和频率而言，肺中的记忆性CD8+ T细胞与脾脏中观察到的CD8+ T细胞不同。该提议的潜在假设是，肺部的记忆性CD8+ T细胞对继发性感染期间的快速回忆反应做出了重大贡献。这一假设将通过(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）确定不同群体的记忆细胞对回忆反应的相对贡献来验证。

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.