Effector T<sub>H</sub>17 Cells Give Rise to Long-Lived T<sub>RM</sub> Cells that Are Essential for an Immediate Response against Bacterial Infection.

Amezcua Vesely, Maria Carolina; Pallis, Paris; Bielecki, Piotr; Low, Jun Siong; Zhao, Jun; Harman, Christian C D; Kroehling, Lina; Jackson, Ruaidhrí et al. · Cell · 2019

basic_science · Level V

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Abstract

Adaptive immunity provides life-long protection by generating central and effector memory T cells and the most recently described tissue resident memory T (T<sub>RM</sub>) cells. However, the cellular origin of CD4 T<sub>RM</sub> 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<sub>RM</sub> cells derive from IL-17A-producing effector (T<sub>H</sub>17) cells following immunization with heat-killed Klebsiella pneumonia (Kp). These exT<sub>H</sub>17 T<sub>RM</sub> 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<sub>H</sub>17 T<sub>RM</sub> cells play an important role in bacterial clearance. Thus, we delineate the origin and function of airway CD4 T<sub>RM</sub> cells during bacterial infection, offering novel strategies for targeted vaccine design.

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