Airway-resident memory CD4 T-cell activation accelerates antigen presentation and T-cell priming in draining lymph nodes

Specialized memory CD4 T cells that reside long-term within tissues are critical components of immunity at portals of pathogen entry. In the lung, such tissue-resident memory (TRM) cells are activated rapidly after infection and promote local inflammation to control pathogen levels before circulating T cells can respond. However, optimal clearance of Influenza A virus can require TRM and responses by other virus-specific T cells that reach the lung only several days after their activation in secondary lymphoid organs. Whether local CD4 TRM sentinel activity can impact the efficiency of T cell activation in secondary lymphoid organs is not clear. Here, we found that recognition of antigen by influenza -primed TRM in the airways promotes more rapid migration of highly activated antigen-bearing dendritic cells to the draining lymph nodes. This in turn accelerated the priming of naive T cells recognizing the same antigen, resulting in newly activated effector T cells reaching the lungs earlier than in mice not harboring TRM. Our findings thus reveal a circuit linking local and regional immunity whereby antigen recognition by TRM improves effector T cell recruitment to the site of infection though enhancing the efficiency of antigen presentation in the draining lymph node.