Immune Cell Biology Laboratory, Department of Biomedicine, University of Basel, University Hospital Basel, CH-4031 Basel, Switzerland.
Personalised Health Basel- Oncology Cluster Basel, University of Basel, Basel, Switzerland.
Sci Immunol. 2021 Jan 8;6(55). doi: 10.1126/sciimmunol.abb6808.
Influenza is a deadly and costly infectious disease, even during flu seasons when an effective vaccine has been developed. To improve vaccines against respiratory viruses, a better understanding of the immune response at the site of infection is crucial. After influenza infection, clonally expanded T cells take up permanent residence in the lung, poised to rapidly respond to subsequent infection. Here, we characterized the dynamics and transcriptional regulation of lung-resident CD4 T cells during influenza infection and identified a long-lived, dependent population that we have termed T resident helper (T) cells. T cells arise in the lung independently of lymph node T follicular helper cells but are dependent on B cells, with which they tightly colocalize in inducible bronchus-associated lymphoid tissue (iBALT). Deletion of in CD4 T cells before heterotypic challenge infection resulted in redistribution of CD4 T cells outside of iBALT areas and impaired local antibody production. These results highlight iBALT as a homeostatic niche for T cells and advocate for vaccination strategies that induce T cells in the lung.
流感是一种致命且代价高昂的传染病，即使在流感季节有有效疫苗的情况下也是如此。为了改进针对呼吸道病毒的疫苗，深入了解感染部位的免疫反应至关重要。流感感染后，克隆扩增的 T 细胞在肺部永久定居，随时准备对后续感染迅速做出反应。在这里，我们描述了流感感染期间肺驻留 CD4 T 细胞的动力学和转录调控，并鉴定了一种称为 T 驻留辅助（T）细胞的长寿、依赖的群体。T 细胞在肺部独立于淋巴结滤泡辅助 T 细胞产生，但依赖于 B 细胞，与 B 细胞紧密共定位于诱导性支气管相关淋巴组织（iBALT）中。在异型挑战感染前，在 CD4 T 细胞中缺失导致 CD4 T 细胞在 iBALT 区域外重新分布，并损害局部抗体产生。这些结果突出了 iBALT 作为 T 细胞的稳态小生境，并主张诱导肺部 T 细胞的疫苗接种策略。
