SLAMF7 and IL-6R define distinct cytotoxic versus helper memory CD8+ T cells

Lucie Loyal, Sarah Warth, Karsten Jürchott, Felix Mölder, Christos Nikolaou, Nina Babel, Mikalai Nienen, Sibel Durlanik, Regina Stark, Beate Kruse, Marco Frentsch, Robert Sabat, Kerstin Wolk and Andreas Thiel ()
Additional contact information
Lucie Loyal: Si-M/“Der Simulierte Mensch” a science framework of Technische Universität Berlin and Charité-Universitätsmedizin Berlin
Sarah Warth: Charité-Universitätsmedizin Berlin
Karsten Jürchott: Charité-Universitätsmedizin Berlin
Felix Mölder: Universität Duisburg-Essen
Christos Nikolaou: Charité-Universitätsmedizin Berlin
Nina Babel: Ruhr Universität Bochum
Mikalai Nienen: Charité-Universitätsmedizin Berlin
Sibel Durlanik: Charité-Universitätsmedizin Berlin
Regina Stark: Sanquin Blood Supply Foundation
Beate Kruse: Si-M/“Der Simulierte Mensch” a science framework of Technische Universität Berlin and Charité-Universitätsmedizin Berlin
Marco Frentsch: Charité-Universitätsmedizin Berlin
Robert Sabat: Charité-Universitätsmedizin Berlin
Kerstin Wolk: Charité-Universitätsmedizin Berlin
Andreas Thiel: Si-M/“Der Simulierte Mensch” a science framework of Technische Universität Berlin and Charité-Universitätsmedizin Berlin

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract The prevailing ‘division of labor’ concept in cellular immunity is that CD8+ T cells primarily utilize cytotoxic functions to kill target cells, while CD4+ T cells exert helper/inducer functions. Multiple subsets of CD4+ memory T cells have been characterized by distinct chemokine receptor expression. Here, we demonstrate that analogous CD8+ memory T-cell subsets exist, characterized by identical chemokine receptor expression signatures and controlled by similar generic programs. Among them, Tc2, Tc17 and Tc22 cells, in contrast to Tc1 and Tc17 + 1 cells, express IL-6R but not SLAMF7, completely lack cytotoxicity and instead display helper functions including CD40L expression. CD8+ helper T cells exhibit a unique TCR repertoire, express genes related to skin resident memory T cells (TRM) and are altered in the inflammatory skin disease psoriasis. Our findings reveal that the conventional view of CD4+ and CD8+ T cell capabilities and functions in human health and disease needs to be revised.

Date: 2020
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DOI: 10.1038/s41467-020-19002-6

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