TY - JOUR
T1 - Lymphatic endothelial cells prime naïve CD8+ T cells into memory cells under steady-state conditions
AU - Vokali, Efthymia
AU - Yu, Shann S.
AU - Hirosue, Sachiko
AU - Rinçon-Restrepo, Marcela
AU - V. Duraes, Fernanda
AU - Scherer, Stefanie
AU - Corthésy-Henrioud, Patricia
AU - Kilarski, Witold W.
AU - Mondino, Anna
AU - Zehn, Dietmar
AU - Hugues, Stéphanie
AU - Swartz, Melody A.
N1 - Funding Information:
The authors are grateful to Yue Wang, Yassin Ben Saida, Xavier Quaglia-Thermes, Giacomo O. Diaceri, Vasiliki Panagiotou, S. Oberle, Cristina Cartoni, E. Anastasiou, Elena Cabello, the EPFL Flow Cytometry Core Facility (Miguel Garcia, Loïc Tauzin, Valérie Glutz) and the University of Chicago Cytometry and Antibody Technology Core (David Leclerc, Mandel Davis, Mike Olson, and Robert Ladd) for technical support and assistance, as well as Maria-Luisa Alegre, Bana Jabri, Albert Bendelac, Amanda W. Lund, Catherine M. Card and Eleonora Simeoni for helpful discussions and suggestions. This work was funded by grants from the Swiss Cancer Research (KFS-3312-08-2013 to M.A.S.), the European Research Council (AdG-323053 to M.A.S.), and the National Institutes of Health (R01 CA219304-01A1 to M.A.S.).
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Lymphatic endothelial cells (LECs) chemoattract naïve T cells and promote their survival in the lymph nodes, and can cross-present antigens to naïve CD8+ T cells to drive their proliferation despite lacking key costimulatory molecules. However, the functional consequence of LEC priming of CD8+ T cells is unknown. Here, we show that while many proliferating LEC-educated T cells enter early apoptosis, the remainders comprise a long-lived memory subset, with transcriptional, metabolic, and phenotypic features of central memory and stem cell-like memory T cells. In vivo, these memory cells preferentially home to lymph nodes and display rapid proliferation and effector differentiation following memory recall, and can protect mice against a subsequent bacterial infection. These findings introduce a new immunomodulatory role for LECs in directly generating a memory-like subset of quiescent yet antigen-experienced CD8+ T cells that are long-lived and can rapidly differentiate into effector cells upon inflammatory antigenic challenge.
AB - Lymphatic endothelial cells (LECs) chemoattract naïve T cells and promote their survival in the lymph nodes, and can cross-present antigens to naïve CD8+ T cells to drive their proliferation despite lacking key costimulatory molecules. However, the functional consequence of LEC priming of CD8+ T cells is unknown. Here, we show that while many proliferating LEC-educated T cells enter early apoptosis, the remainders comprise a long-lived memory subset, with transcriptional, metabolic, and phenotypic features of central memory and stem cell-like memory T cells. In vivo, these memory cells preferentially home to lymph nodes and display rapid proliferation and effector differentiation following memory recall, and can protect mice against a subsequent bacterial infection. These findings introduce a new immunomodulatory role for LECs in directly generating a memory-like subset of quiescent yet antigen-experienced CD8+ T cells that are long-lived and can rapidly differentiate into effector cells upon inflammatory antigenic challenge.
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U2 - 10.1038/s41467-019-14127-9
DO - 10.1038/s41467-019-14127-9
M3 - Article
C2 - 31988323
AN - SCOPUS:85078337421
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 538
ER -