#A 83-01 ; #9094360 ;
J Exp Med. 2024 Feb 5;221(2):e20230488. doi: 10.1084/jem.20230488.
Michael Delacher # 1 2 3 4, Lisa Schmidleithner # 1 2, Malte Simon # 1 5 6, Philipp Stüve # 1 2, Lieke Sanderink 1 2, Agnes Hotz-Wagenblatt 7, Marina Wuttke 1 2, Kathrin Schambeck 1 2, Brigitte Ruhland 1 2, Veronika Hofmann 1 2, Sebastian Bittner 1 2, Uwe Ritter 1 2, Asmita Pant 1 2, Sara Salome Helbich 3 4, Morten Voss 3 4, Niels A Lemmermann 4 8 9, Lisa Bessiri-Schake 3 4, Toszka Bohn 3 4, Andreas Eigenberger 10, Ayse Nur Menevse 1 11, Claudia Gebhard 1, Nicholas Strieder 1, Hinrich Abken 1 12, Michael Rehli 1 13, Jochen Huehn 14 15 16, Philipp Beckhove 1 11 13, Thomas Hehlgans 1 2, Henrik Junger 17, Edward K Geissler 17, Lukas Prantl 10, Jens M Werner 17, Christian Schmidl 1, Benedikt Brors 5 18 6 19 20, Charles D Imbusch 3 4 6, Markus Feuerer 1 2
- PMID: 38226976
- PMCID: PMC10791561
- DOI: 10.1084/jem.20230488
Abstract
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.