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The effector program of human CD8 T cells can support tissue remodeling abilities.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Abstract Paper: 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 healthy donor skin and adipose tissue with 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE223989 | GEO | 2023/11/20

REPOSITORIES: GEO

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

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

Project description: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-Ã¯ÂÂ§ 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.

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