Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy subjects

Sci Immunol, 2019 · DOI: 10.1126/sciimmunol.aav8995 · Published: July 5, 2019

Simple Explanation

Tissue-resident memory T cells (TRM) stay in tissues and defend against recurring problems. In the skin, these cells use markers like CD103 and CD69 to stay put. This study found that skin TRM can actually leave the tissue and enter the bloodstream. They also discovered a related group of cells in the blood that can move to other skin areas. This challenges the idea that these cells are stuck in one place and shows they can move around to protect the skin in different locations.

Study Duration

Not specified

Participants

Healthy human subjects and chylothorax patients

Evidence Level

Not specified

Key Findings

1
Human skin CD4+ TRM can downregulate CD69 and exit the skin.
2
A population of CD4+CD103+ T cells exists in human blood and lymph that shares characteristics with skin TRM.
3
Circulating CD4+CD103+ TRM can migrate to and populate secondary skin sites, re-expressing CD69.

Research Summary

This study investigates the migratory behavior of human skin-resident memory T cells (TRM), challenging the concept of strict tissue compartmentalization. The research identifies a circulating population of CD4+CD103+ T cells in human blood and lymph that shares phenotypic, functional, and clonal characteristics with skin TRM. Using a skin xenograft model, the study demonstrates that cutaneous CD4+CD103+ TRM can re-enter circulation and migrate to secondary skin sites, reassuming a TRM phenotype.

Practical Implications

Challenging Current Concepts

The study challenges the current understanding of T cell memory, suggesting that CD4+ TRM are not strictly confined to tissues but can recirculate.

New Avenues for Therapeutic Intervention

The discovery of circulating CD4+CLA+CD103+ T cells facilitates the study and manipulation of skin TRM in various contexts, including autoimmunity, infection, and tissue repair.

Understanding Skin Immunity

The research provides insights into the dynamics of skin immunity and the role of TRM in maintaining tissue homeostasis and responding to challenges.

Study Limitations

1
Tissue damage associated with surgical skin acquisition may have impacted TRM mobilization.
2
The precise role of the CD4+CLA+CD103+ population in skin immunity and homeostasis remains to be established in vivo.
3
Whether tissue-exit of cutaneous CD4+CLA+CD103+ T cells is a stochastic process or actively triggered mobilization remains to be determined.

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