Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Curr Opin Virol. 2024 Apr;65:101397. doi: 10.1016/j.coviro.2024.101397. Epub 2024 Mar 8.
Influenza virus is an important human pathogen with significant pandemic potential. Tissue-resident memory T cells (Trm) in the lung provide critical protection against influenza, but unlike Trm at other mucosal sites, Trm in the respiratory tract (RT) are subject to rapid attrition in mice, mirroring the decline in protective immunity to influenza virus over time. Conversely, dysfunctional Trm can drive fibrosis in aged mice. The requirement for local antigen to induce and maintain RT Trm must be considered in vaccine strategies designed to induce this protective immune subset. Here, we discuss recent studies that inform our understanding of influenza-specific respiratory Trm, and the factors that influence their development and persistence. We also discuss how these biological insights are being used to develop vaccines that induce Trm in the RT, despite the limitations to monitoring Trm in humans.
流感病毒是一种重要的人类病原体，具有重大的大流行潜力。肺部组织驻留记忆 T 细胞（Trm）为抵御流感提供了关键保护，但与其他黏膜部位的 Trm 不同，呼吸道（RT）中的 Trm 在小鼠中会迅速耗竭，反映了随着时间的推移，对流感病毒的保护性免疫逐渐下降。相反，功能失调的 Trm 会导致老年小鼠纤维化。在设计旨在诱导这种保护性免疫亚群的疫苗策略时，必须考虑到局部抗原诱导和维持 RT Trm 的需求。在这里，我们讨论了最近的研究，这些研究使我们对流感特异性呼吸 Trm 及其影响其发育和持久性的因素有了更深入的了解。我们还讨论了如何利用这些生物学见解来开发能够在 RT 中诱导 Trm 的疫苗，尽管在监测人类 Trm 方面存在限制。
