The Vast Majority of CLA+ T Cells Are Resident in Normal Skin
Abstract
There are T cells within normal, noninflamed skin that most likely conduct immunosurveillance and are implicated in the development of psoriasis. We isolated T cells from normal human skin using both established and novel methods. Skin resident T cells expressed high levels of CLA, CCR4, and CCR6, and a subset expressed CCR8 and CXCR6. Skin T cells had a remarkably diverse TCR repertoire and were mostly Th1 memory effector cells with smaller subsets of central memory, Th2, and functional T regulatory cells. We isolated a surprising number of nonexpanded T cells from normal skin. To validate this finding, we counted T cells in sections of normal skin and determined that there are ∼1 × 106 T cells/cm2 normal skin and an estimated 2 × 1010 T cells in the entire skin surface, nearly twice the number of T cells in the circulation. Moreover, we estimate that 98% of CLA+ effector memory T cells are resident in normal skin under resting conditions. These findings demonstrate that there is a large pool of memory T cells in normal skin that can initiate and perpetuate immune reactions in the absence of T cell recruitment from the blood.
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Isolation of T cells from human tissues often requires enzymatic digestion with collagenases, which may affect the expression of certain proteins, particularly chemokine receptors such as CCR6, due to their large structure and multiple transmembrane domains.
“Isolation of T cells from human tissues often requires enzymatic digestion with collagenases, which may affect the expression of certain proteins, particularly chemokine receptors, such as CCR6 [279], due to their large structure and multiple transmembrane domains.”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [279]
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- Authors
- Clark, R. A., Chong, B., Mirchandani, N., Brinster, N. K., Yamanaka, K.-I., Dowgiert, R. K., & Kupper, T. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Henry Ford Hospital (US)
- St. Luke's-Roosevelt Hospital Center (US)
- Lahey Hospital and Medical Center (US)
- Mie University (JP)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-04-01
- Volume
- 176
- Issue
- 7
- Pages
- 4431-4439
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2113765099
- Cited by
- 796
- References
- 38
- Citations by year
- 2026: 16 · 2025: 34 · 2024: 40 · 2023: 44 · 2022: 42 · 2021: 59 · 2020: 52 · 2019: 46 · 2018: 48 · 2017: 44 · 2016: 53 · 2015: 46 · 2014: 57 · 2013: 39 · 2012: 37
- FWCI
- 11.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R37 AI 25082, R37AI025082)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR042689, P30-AR42689, T32 AR 07098, R01AR065807, T32AR007098)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- skin-resident T cells, psoriasis, T cell receptor diversity, central memory T cells, regulatory T cells, Th2 cells, CCR4, CCR6, CCR8, CXCR6, T cell homing
- MeSH terms
- Antigens, Differentiation, T-Lymphocyte, Antigens, Neoplasm, Cell Movement, Cell Separation, Cells, Cultured, Gene Expression Regulation, Humans, Immunologic Memory, Membrane Glycoproteins, Phenotype, Protein Binding, Receptors, Antigen, T-Cell, Skin, T-Lymphocytes, E-Selectin
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