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Sci Immunol. 2019 Jul 5;4(37). pii: eaav8995. doi: 10.1126/sciimmunol.aav8995.

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

Author information

1
Department of Biosciences, University of Salzburg, Salzburg, Austria.
2
Benaroya Research Institute, Seattle, WA 98101, USA.
3
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4
Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA.
5
Experimental and Clinical Cell Therapy Institute, Spinal Cord and Tissue Regeneration Center, Paracelsus Medical University, Salzburg, Austria.
6
Benaroya Research Institute, Seattle, WA 98101, USA. campbell@benaroyaresearch.org iris.gratz@sbg.ac.at.
7
Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
8
Department of Biosciences, University of Salzburg, Salzburg, Austria. campbell@benaroyaresearch.org iris.gratz@sbg.ac.at.
9
EB House Austria, Department of Dermatology, University Hospital of the Paracelsus Medical University, Salzburg, Austria.

Abstract

Tissue-resident memory T cells (TRM) persist locally in nonlymphoid tissues where they provide frontline defense against recurring insults. TRM at barrier surfaces express the markers CD103 and/or CD69, which function to retain them in epithelial tissues. In humans, neither the long-term migratory behavior of TRM nor their ability to reenter the circulation and potentially migrate to distant tissue sites has been investigated. Using tissue explant cultures, we found that CD4+CD69+CD103+ TRM in human skin can down-regulate CD69 and exit the tissue. In addition, we identified a skin-tropic CD4+CD69-CD103+ population in human lymph and blood that is transcriptionally, functionally, and clonally related to the CD4+CD69+CD103+ TRM population in the skin. Using a skin xenograft model, we confirmed that a fraction of the human cutaneous CD4+CD103+ TRM population can reenter circulation and migrate to secondary human skin sites where they reassume a TRM phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4+ T cell memory in humans.

PMID:
31278120
DOI:
10.1126/sciimmunol.aav8995

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