Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection

Adaptive immunity provides life-long protection by generating central and effector memory T cells and the most recently described tissue resident memory T (T RM ) cells. However, the cellular origin of CD4 T RM cells and their contribution to host defense remain elusive. Using IL-17A tracking-fate mouse models, we found that a significant fraction of lung CD4 T RM cells derive from IL-17A-producing effector (T H 17) cells following immunization with heat-killed Klebsiella pneumonia (Kp). These exT H 17 T RM cells are maintained in the lung by IL-7, produced by lymphatic endothelial cells. During a memory response, neither antibodies, γδ T cells, nor circulatory T cells are sufficient for the rapid host defense required to eliminate Kp. Conversely, using parabiosis and depletion studies, we demonstrated that exT H 17 T RM cells play an important role in bacterial clearance. Thus, we delineate the origin and function of airway CD4 T RM cells during bacterial infection, offering novel strategies for targeted vaccine design.