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

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Abstract

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 affect 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 promoted more rapid migration of highly activated antigen-bearing DC 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.

Authors

Caroline M. Finn, Kunal Dhume, Eugene Baffoe, Lauren A. Kimball, Tara M. Strutt, K. Kai McKinstry