The effector program of human CD8 T cells supports tissue remodeling

Area of Science:

• Immunology
• Regenerative Medicine
• Cell Biology

Background:

• CD8 T lymphocytes are traditionally recognized for their cytotoxic functions.
• The potential of human CD8 T cells to induce tissue regeneration remains largely unexplored.

Purpose of the Study:

• To investigate the capacity of human CD8 T cells to promote tissue regeneration.
• To identify the mechanisms and molecular players involved in CD8 T cell-mediated tissue remodeling.

Main Methods:

• Utilized antigen-specific assay systems to assess CD8 T cell functions.
• Employed single-cell gene expression analysis to identify specific CD8 T cell populations.
• Investigated the role of epidermal growth factor receptor (EGFR) and effector cytokines (IFN-γ, TNF) in tissue remodeling.

Main Results:

• Human CD8 T cells demonstrated both cytotoxic and tissue remodeling capabilities.
• Activated CD8 T cells produced amphiregulin (AREG), sensitizing epithelial cells for enhanced regeneration.
• Blocking EGFR or effector cytokines inhibited tissue remodeling, which supported tumor spheroid and organoid growth.
• Identified AREG+ tissue-resident CD8 T cells in human skin and adipose tissue with regenerative potential.

Conclusions:

• Human CD8 T cells possess a previously unrecognized ability to induce tissue regeneration.
• Amphiregulin (AREG) production by CD8 T cells is a key mechanism in promoting epithelial repair and tissue remodeling.
• These findings have implications for understanding CD8 T cell biology in tumors and developing novel therapeutic strategies.