Lymphatic endothelial cells prime naïve CD8+ T cells into memory cells under steady-state conditions

Efthymia Vokali, Shann S. Yu, Sachiko Hirosue, Marcela Rinçon-Restrepo, Fernanda Duraes, Stefanie Scherer, Patricia Corthésy-Henrioud, Witold W. Kilarski, Anna Mondino, Dietmar Zehn, Stéphanie Hugues and Melody A. Swartz ()
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Efthymia Vokali: École Polytechnique Fédérale de Lausanne (EPFL)
Shann S. Yu: École Polytechnique Fédérale de Lausanne (EPFL)
Sachiko Hirosue: École Polytechnique Fédérale de Lausanne (EPFL)
Marcela Rinçon-Restrepo: École Polytechnique Fédérale de Lausanne (EPFL)
Fernanda Duraes: Faculty of Medicine, University of Geneva
Stefanie Scherer: Swiss Vaccine Research Institute
Patricia Corthésy-Henrioud: École Polytechnique Fédérale de Lausanne (EPFL)
Witold W. Kilarski: École Polytechnique Fédérale de Lausanne (EPFL)
Anna Mondino: San Raffaele Scientific Institute
Dietmar Zehn: Swiss Vaccine Research Institute
Stéphanie Hugues: Faculty of Medicine, University of Geneva
Melody A. Swartz: École Polytechnique Fédérale de Lausanne (EPFL)

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-019-14127-9

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