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Skin resident memory CD8+ T cells are phenotypically and functionally distinct from circulating populations and lack
J A Seidel1, M Vukmanovic-Stejic1, B Muller-Durovic1,2
1Division of Infection and Immunity, University College London, UK.
Clinical and Experimental Immunology
|July 22, 2018
Summary
Skin resident memory CD8+ T cells (TRM) are phenotypically and functionally distinct from circulating T cells. Understanding these differences in TRM is crucial for developing new disease treatment strategies.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Skin resident memory CD8+ T lymphocytes (TRM) play a critical role in immune surveillance and disease pathogenesis.
- Understanding the unique characteristics of TRM is essential for developing targeted immunotherapies.
Purpose of the Study:
- To investigate the phenotypic and functional distinctions between human skin-resident CD8+ TRM and circulating CD8+ T cells.
- To explore the potential for manipulating TRM function for therapeutic benefit.
Main Methods:
- Isolation and characterization of CD8+ TRM from healthy human skin.
- Comparison of TRM with circulating CD8+ T cells using flow cytometry and functional assays.
- In vitro activation studies and blockade of inhibitory receptors (e.g., PD-1).
Main Results:
- Skin CD8+ TRM exhibited distinct phenotypes, including lower expression of KLRG1, CD57, perforin, and granzyme B compared to circulating counterparts.
- In vitro activation induced granzyme B expression in TRM, which was further enhanced by PD-1 blockade.
- A subset of CD8+ TRM secreted high levels of TNF-α and IL-2, a unique cytokine profile not commonly observed in circulating T cells.
Conclusions:
- Cutaneous CD8+ TRM are phenotypically and functionally diverse, differing significantly from circulating CD8+ T cells.
- Standard markers for T cell differentiation in blood are not applicable to skin TRM.
- Environmental signals in the skin stringently control the function of cutaneous TRM.
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