CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin

Area of Science:

• Immunology
• Dermatology
• Cell Biology

Background:

• Human skin contains two T cell populations of equal size.
• CCR8 expression on T cells is influenced by T cell receptor engagement and the skin microenvironment.

Purpose of the Study:

• To investigate the in vivo relationship between CCR8-expressing (CCR8+) and CCR8-non-expressing (CCR8-) skin T cells.
• To determine if CCR8 expression can define distinct T cell subsets in human skin.

Main Methods:

• Phenotypic, functional, and transcriptomic analyses of skin T cells.
• Conventional and high-throughput sequencing of T cell receptor beta chain (TRB) gene rearrangements.
• In vitro assessment of phenotypic stability and telomere erosion.

Main Results:

• CCR8+ skin T cells exhibit characteristics of resident memory T cells, including homeostatic proliferation and expression of tissue-retention markers (CD103, CD69).
• CCR8- skin T cells are heterogeneous, containing exhausted, senescent, and effector T cells.
• CCR8-defined populations are clonotypically distinct, suggesting different origins and responses to stimuli.
• Both CCR8+ and CCR8- T cells showed phenotypic stability in vitro with similar telomere erosion.

Conclusions:

• CCR8 expression is a reliable marker for identifying long-lived resident memory T cells in human skin.
• CCR8-defined populations represent distinct T cell lineages with unique ontogenies.
• This classification provides a new framework for understanding T cell heterogeneity and function in the skin.