Tissue-resident memory T cell reactivation by diverse antigen-presenting cells imparts distinct functional responses.

The Journal of Experimental Medicine
Jun Siong LowSusan M Kaech

Abstract

CD8+ tissue-resident memory T cells (TRM cells) are poised at the portals of infection and provide long-term protective immunity. Despite their critical roles, the precise mechanics governing TRM cell reactivation in situ are unknown. Using a TCR-transgenic Nur77-GFP reporter to distinguish "antigen-specific" from "bystander" reactivation, we demonstrate that lung CD8+ TRM cells are reactivated more quickly, yet less efficiently, than their counterparts in the draining LNs (TLN cells). Global profiling of reactivated memory T cells revealed tissue-defined and temporally regulated recall response programs. Unlike the reactivation of CD8+ TLN cells, which is strictly dependent on CD11c+XCR1+ APCs, numerous antigen-presenting partners, both hematopoietic and non-hematopoietic, were sufficient to reactivate lung CD8+ TRM cells, but the quality of TRM cell functional responses depended on the identity of the APCs. Together, this work uncovers fundamental differences in the activation kinetics, mechanics, and effector responses between CD8+ memory T cells in peripheral vs. lymphoid organs, revealing a novel tissue-specific paradigm for the reactivation of memory CD8+ T cells.

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Citations

Dec 30, 2020·Vaccines·Nicholas W Lukacs, Carrie-Anne Malinczak
Feb 15, 2021·Ecotoxicology and Environmental Safety·Yingchun ZhangZhixian Gao
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Datasets Mentioned

BETA
GSE147908

Methods Mentioned

BETA
RNA-seq
PCA
flow cytometry
bronchoalveolar lavage
PCR
HTseq
confocal microscopy

Software Mentioned

Imaris
Enrichr

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