The effector program of human CD8 T cells can promote both target cell killing and tissue remodeling

CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a regenerative program is not understood. Here, antigen-specific assay systems revealed that human CD8 T cells not only mediated cytotoxicity, but also promoted bystander fibroblast and epithelial cell activation, leading to the production of tissue regenerative factors. Tissue remodeling by CD8 T cells could be inhibited by blocking the epidermal growth factor receptor or the effector cytokines IFN-ï§ and TNF. The regenerative program also enhanced tumor spheroid and primary organoid growth. Using single-cell chromatin accessibility and gene expression analysis, we identified a tissue-resident CD8 T cell population in healthy donor skin and adipose tissue with a strong TCR clonal relation to blood PD1+TIGIT+ CD8 T cells with tissue remodeling abilities. Our findings may help to understand CD8 in the tumor micromilieu and become relevant for the design of CD8 T-cell therapies.EGA study EGAS00001006960