T resident helper cells promote humoral responses in the lung.

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.