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Cited by 374Liver physiology and pathologyT-cell and B-cell ImmunologyHepatitis B Virus Studies

Resident human hepatitis lymphocytes are phenotypically different from circulating lymphocytes

Norris, Suzanne, Collins, Clive, Doherty, Derek G., Smith, Fiona, McEntee, Gerry, Traynor, Oscar, Nolan, Niamh, Hegarty, John, O'Farrelly, Cliona·1998·Journal of Hepatology
DOI 10.1016/s0168-8278(98)80206-7
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Abstract

Background/aims Murine and human studies have documented the existence of subpopulations of lymphocytes in particular tissues that differ phenotypically and functionally from those in peripheral blood and may mature locally. Since little is known about lymphocyte subpopulations in the normal human liver, we have analysed the surface phenotypes of lymphocytes isolated from liver specimens taken from 15 donors at the time of liver transplantation, and compared these with those of peripheral blood lymphocytes. Methods Hepatic lymphocytes were prepared by mechanical dissociation and enzymatic digestion of liver tissue. The cells were stained with a panel of monoclonal antibodies (CD3, CD4, CD8, CD19, CD56, gammadeltaTCR, alphabetaTCR, CD8alpha-chain, CD8alphabeta dimer), and analysed by flow cytometry. In situ characterisation of hepatic lymphocytes was by haematoxylin and eosin staining of fixed liver sections and by immunohistochemical staining for common leukocyte antigen and CD3. Results Significant numbers of hepatic T lymphocytes were localised to the portal tracts and parenchyma of normal liver specimens. Flow cytometry revealed that the CD4/CD8 ratio (1:3.5) was consistently reversed compared with that in peripheral blood (2:1). Other lymphocyte populations identified include double positive CD3+CD4+CD8+ cells which accounted for a mean of 5.5% (range 3-11.6%) of hepatic CD3+ cells compared with 1.3% in blood (range 0.7-3.6%; p < 0.007), and double negative CD3+ CD4-8- cells (14.5%; range 2.7-29% compared with 5.0%; range 2.1-10.8%, p < 0.02). Over 15% (range 6.8-34%) of all hepatic CD3+ cells expressed a gammadeltaTCR compared to 2.7% (range 0.9-4.7%) of CD3+ peripheral blood lymphocytes (p < 0.004) and almost 50% of these coexpressed CD8. The CD8 alpha-chain was expressed without the beta-chain (CD8alpha+beta-) by 15.4% (range 4-29.1%) of hepatic T cells, but this phenotype was undetectable among peripheral blood lymphocytes (p < 0.009). Cells expressing both the T cell marker CD3 and the natural killer cell marker CD56 constituted 31.6% (range 14-54%) of all hepatic CD3+ lymphocytes but were rarely present amongst peripheral blood lymphocytes (0-6%; p < 0.0001). Conclusions These data are the first to describe and quantify unconventional T lymphocyte subpopulations in the normal adult human liver which may have specialised functions in regional immune responses and which may differentiate locally. These findings have important implications for our understanding of hepatic immunoregulation and the pathogenic mechanisms involved in viral and immune-mediated liver disease and allograft rejection.

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Authors
Norris, S., Collins, C., Doherty, D. G., Smith, F., McEntee, G., Traynor, O., Nolan, N., Hegarty, J., & O'Farrelly, C.
Affiliations
University College Dublin (IE)
ORCID
Venue
Journal of Hepatology
Publisher
Elsevier BV
Published
1998-01
Volume
28
Issue
1
Pages
84-90
ISSN
0168-8278 (ISSN-L)
DOI
10.1016/s0168-8278(98)80206-7
OpenAlex
W1972264376
Cited by
374
References
30
Citations by year
2026: 2 · 2025: 4 · 2024: 6 · 2023: 11 · 2022: 15 · 2021: 21 · 2020: 14 · 2019: 9 · 2018: 14 · 2017: 17 · 2016: 23 · 2015: 10 · 2014: 10 · 2013: 19 · 2012: 21
FWCI
6.11
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Journal of Hepatology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Health Research Board
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
Keywords
hepatic lymphocytes, liver, T cell subsets, CD4/CD8 ratio, CD4+CD8+ double-positive T cells, double-negative T cells, γδ T cells, CD19, CD56, liver transplantation, peripheral blood lymphocytes, lymphocyte phenotype
MeSH terms
Adolescent, Adult, Animals, Antibodies, Monoclonal, Child, Female, Humans, Liver, Lymphocytes, Male, Middle Aged, Reference Values, T-Lymphocytes, Antigens, CD, Immunophenotyping, Lymphocyte Subsets, Receptors, Antigen, T-Cell, gamma-delta, Mice

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