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The effector program of human CD8 T cells supports tissue remodeling.

The Journal of experimental medicine

Authors: Michael Delacher, Lisa Schmidleithner, Malte Simon, Philipp Stüve, Lieke Sanderink, Agnes Hotz-Wagenblatt, Marina Wuttke, Kathrin Schambeck, Brigitte Ruhland, Veronika Hofmann, Sebastian Bittner, Uwe Ritter, Asmita Pant, Sara Salome Helbich, Morten Voss, Niels A Lemmermann, Lisa Bessiri-Schake, Toszka Bohn, Andreas Eigenberger, Ayse Nur Menevse, Claudia Gebhard, Nicholas Strieder, Hinrich Abken, Michael Rehli, Jochen Huehn, Philipp Beckhove, Thomas Hehlgans, Henrik Junger, Edward K Geissler, Lukas Prantl, Jens M Werner, Christian Schmidl, Benedikt Brors, Charles D Imbusch, Markus Feuerer

CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a tissue regeneration program is poorly understood. Here, antigen-specific assay systems revealed that human CD8 T cells not only mediated cytotoxicity but also promoted tissue remodeling. Activated CD8 T cells could produce the epidermal growth factor receptor (EGFR)-ligand amphiregulin (AREG) and sensitize epithelial cells for enhanced regeneration potential. Blocking the EGFR or the effector cytokines IFN-γ and TNF could inhibit tissue remodeling. This regenerative program enhanced tumor spheroid and stem cell-mediated organoid growth. Using single-cell gene expression analysis, we identified an AREG+, tissue-resident CD8 T cell population in skin and adipose tissue from patients undergoing abdominal wall or abdominoplasty surgery. These tissue-resident CD8 T cells showed a strong TCR clonal relation to blood PD1+TIGIT+ CD8 T cells with tissue remodeling abilities. These findings may help to understand the complex CD8 biology in tumors and could become relevant for the design of therapeutic T cell products.

© 2024 Delacher et al.

PMID: 38226976

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