The effector program of human CD8 T cells supports tissue remodeling

作者：Michael Delacher, Lisa M. 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 Michael Voss, Niels A. W. Lemmermann, Lisa Bessiri-Schake, Toszka Bohn, Andreas Eigenberger, Ayse N. Menevse, Claudia Gebhard, Nicholas Strieder, Hinrich Abken, Michael Rehli, Jochen Huehn, Philipp Beckhove, Thomas Hehlgans, Henrik Horst Gerhard Junger, Edward Kenneth Geissler, Lukas Prantl, Jens Martin Werner, Christian Schmidl, Benedikt Brors, Charles David Imbusch, Markus Feuerer · 发表于：The Journal of Experimental Medicine · 年份：2023 · DOI：10.1084/jem.20230488 · 被引用次数：31 · 研究领域：CAR-T cell therapy research、Immunotherapy and Immune Responses、Immune Cell Function and Interaction

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.