Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells

Rei Watanabe, Ahmed Gehad, Chao Yang, Laura L. Scott, Jessica E. Teague, Christoph Schlapbach, Christopher P. Elco, Victor Huang, Tiago R. Matos, Thomas S. Kupper, Rachael A. Clark

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

The skin of an adult human contains about 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice, but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in human skin. We discriminated resident from recirculating T cells in human-engrafted mice and lymphoma patients using alemtuzumab, a medication that depletes recirculating T cells from skin, and then analyzed these T cell populations in healthy human skin. All nonrecirculating resident memory T cells (TRM) expressed CD69, but most were CD4+, CD103-, and located in the dermis, in contrast to studies in mice. Both CD4+ and CD8+ CD103+ TRM were enriched in the epidermis, had potent effector functions, and had a limited proliferative capacity compared to CD103- TRM. TRM of both types had more potent effector functions than recirculating T cells. We observed two distinct populations of recirculating T cells, CCR7+/L-selectin+ central memory T cells (TCM) and CCR7+/L-selectin- T cells, which we term migratory memory T cells (TMM). Circulating skin-tropic TMM were intermediate in cytokine production between TCM and effector memory T cells. In patients with cutaneous T cell lymphoma, malignant TCM and TMM induced distinct inflammatory skin lesions, and TMM were depleted more slowly from skin after alemtuzumab, suggesting that TMM may recirculate more slowly. In summary, human skin is protected by four functionally distinct populations of T cells, two resident and two recirculating, with differing territories of migration and distinct functional activities.

Original languageEnglish (US)
Article number279ra39
JournalScience Translational Medicine
Volume7
Issue number279
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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T-Lymphocytes
Skin
Population
L-Selectin
Cutaneous T-Cell Lymphoma
Dermis
Epidermis
Lymphoma
Epithelium
Cytokines

ASJC Scopus subject areas

  • Medicine(all)

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Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells. / Watanabe, Rei; Gehad, Ahmed; Yang, Chao; Scott, Laura L.; Teague, Jessica E.; Schlapbach, Christoph; Elco, Christopher P.; Huang, Victor; Matos, Tiago R.; Kupper, Thomas S.; Clark, Rachael A.

In: Science Translational Medicine, Vol. 7, No. 279, 279ra39, 01.01.2015.

Research output: Contribution to journalArticle

Watanabe, R, Gehad, A, Yang, C, Scott, LL, Teague, JE, Schlapbach, C, Elco, CP, Huang, V, Matos, TR, Kupper, TS & Clark, RA 2015, 'Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells', Science Translational Medicine, vol. 7, no. 279, 279ra39. https://doi.org/10.1126/scitranslmed.3010302
Watanabe, Rei ; Gehad, Ahmed ; Yang, Chao ; Scott, Laura L. ; Teague, Jessica E. ; Schlapbach, Christoph ; Elco, Christopher P. ; Huang, Victor ; Matos, Tiago R. ; Kupper, Thomas S. ; Clark, Rachael A. / Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells. In: Science Translational Medicine. 2015 ; Vol. 7, No. 279.
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AU - Schlapbach, Christoph

AU - Elco, Christopher P.

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AU - Kupper, Thomas S.

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AB - The skin of an adult human contains about 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice, but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in human skin. We discriminated resident from recirculating T cells in human-engrafted mice and lymphoma patients using alemtuzumab, a medication that depletes recirculating T cells from skin, and then analyzed these T cell populations in healthy human skin. All nonrecirculating resident memory T cells (TRM) expressed CD69, but most were CD4+, CD103-, and located in the dermis, in contrast to studies in mice. Both CD4+ and CD8+ CD103+ TRM were enriched in the epidermis, had potent effector functions, and had a limited proliferative capacity compared to CD103- TRM. TRM of both types had more potent effector functions than recirculating T cells. We observed two distinct populations of recirculating T cells, CCR7+/L-selectin+ central memory T cells (TCM) and CCR7+/L-selectin- T cells, which we term migratory memory T cells (TMM). Circulating skin-tropic TMM were intermediate in cytokine production between TCM and effector memory T cells. In patients with cutaneous T cell lymphoma, malignant TCM and TMM induced distinct inflammatory skin lesions, and TMM were depleted more slowly from skin after alemtuzumab, suggesting that TMM may recirculate more slowly. In summary, human skin is protected by four functionally distinct populations of T cells, two resident and two recirculating, with differing territories of migration and distinct functional activities.

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