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Publication

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

Cell | 2019

Adaptive immunity provides life-long protection by generating central and effector memory T cells and the most recently described tissue resident memory T (TRM) cells. However, the cellular origin of CD4 TRM 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 TRM cells derive from IL-17A-producing effector (TH17) cells following immunization with heat-killed Klebsiella pneumonia (Kp). These exTH17 TRM 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 exTH17 TRM cells play an important role in bacterial clearance. Thus, we delineate the origin and function of airway CD4 TRM cells during bacterial infection, offering novel strategies for targeted vaccine design.

Pubmed ID: 31442406 RIS Download

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Associated grants

Agency: NIGMS NIH HHS, United States
Id: R01 GM131642
Agency: NIAID NIH HHS, United States
Id: R01 AI127429
Agency: NIDDK NIH HHS, United States
Id: R01 DK103744
Agency: NCATS NIH HHS, United States
Id: UL1 TR001863
Agency: NIAMS NIH HHS, United States
Id: R01 AR060744
Agency: NHGRI NIH HHS, United States
Id: R01 HG008383
Agency: NIAID NIH HHS, United States
Id: R01 AI113040
Agency: Howard Hughes Medical Institute, United States

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RRID:SCR_016342

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