CCR8 expression defines tissue-resident memory T cells in human skin

McCully, Michelle L., Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938, Andrews, Robert, Jones, Rhiannon E., Miners, Kelly L., Roger, Laureline, Baird, Duncan M. ORCID: https://orcid.org/0000-0001-8408-5467, Cameron, Mark J., Jessop, Zita M., Whitaker, Iain S., Davies, Eleri L., Price, David A. and Moser, Bernhard ORCID: https://orcid.org/0000-0002-4354-4572 2018. CCR8 expression defines tissue-resident memory T cells in human skin. Journal of Immunology 200 (5) , pp. 1639-1650. 10.4049/jimmunol.1701377

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Abstract

Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is regulated by TCR engagement and the skin tissue microenvironment. To extend these observations, we examined the relationship between CCR8+ and CCR8− skin T cells in vivo. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue localization (CD103) and retention (CD69) markers, low levels of inhibitory receptors (programmed cell death protein 1, Tim-3, LAG-3), and a lack of senescence markers (CD57, killer cell lectin-like receptor subfamily G member 1). In contrast, CCR8− skin T cells are heterogeneous and comprise variable numbers of exhausted (programmed cell death protein 1+), senescent (CD57+, killer cell lectin-like receptor subfamily G member 1+), and effector (T-bethi, Eomeshi) T cells. Importantly, conventional and high-throughput sequencing of expressed TCR β-chain (TRB) gene rearrangements showed that these CCR8-defined populations are clonotypically distinct, suggesting unique ontogenies in response to separate antigenic challenges and/or stimulatory conditions. Moreover, CCR8+ and CCR8− skin T cells were phenotypically stable in vitro and displayed similar levels of telomere erosion, further supporting the likelihood of a nonlinear differentiation pathway. On the basis of these results, we propose that long-lived memory T cells in human skin can be defined by the expression of CCR8.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) Medicine
Additional Information:	This article is distributed under the terms of the CC BY 4.0 Unported license.
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Date of First Compliant Deposit:	29 March 2018
Date of Acceptance:	27 November 2017
Last Modified:	11 Oct 2023 21:53
URI:	https://orca.cardiff.ac.uk/id/eprint/110398

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