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

LOW, JUN SIONG; FARSAKOGLU, YAGMUR; AMEZCUA VESELY, MARIA CAROLINA; SEFIK, ESEN; KELLY, JOSEPH B.; HARMAN, CHRISTIAN C.D.; JACKSON, RUAIDHRI; SHYER, JUSTIN A.; JIANG, XIAODONG; CAULEY, LINDA S.; FLAVELL, RICHARD A.; KAECH, SUSAN M.

JOURNAL OF EXPERIMENTAL MEDICINE

ROCKEFELLER UNIV PRESS

Año: 2020 vol. 217

0022-1007

D8+ 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 kineti