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Cited by 209T-cell and B-cell ImmunologyLiver physiology and pathologyTransplantation: Methods and Outcomes

Antigen-Specific Primary Activation of CD8+ T Cells Within the Liver

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Bertolino, Patrick, Bowen, David G, McCaughan, Geoffrey W, Fazekas de St. Groth, Barbara·2001·The Journal of Immunology
DOI 10.4049/jimmunol.166.9.5430
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Abstract

It is generally accepted that naive T cells recirculate via the blood and lymph, but do not enter nonlymphoid tissues without prior activation and differentiation. In this study, we demonstrate that the liver is an exception to this rule. Naive Des-TCR transgenic CD8+ T cells specific for H-2Kb were selectively retained in the liver within a few minutes of adoptive transfer into transgenic Met-Kb mice expressing H-2Kb in the liver. Activated CD8+ cells were found in the liver, but not the blood, as soon as 2 h after transfer and underwent cell division and started to recirculate within 24 h of transfer. In contrast, CD8+ cells activated in the lymph nodes remained sequestered at that site for 2 days before entering the blood. Our results therefore suggest that, in addition to its previously described role as a non Ag-specific activated T cell graveyard, the liver is involved in Ag-specific activation of naive recirculating CD8+ T cells. This particular property of the liver, combined with the previously demonstrated ability of hepatocytes to induce tolerance by means of premature CD8+ T cell death, may be a major mechanism contributing to the acceptance of liver allografts and the chronicity of viral hepatitis.

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  • These results proved that circulating T cells have full access to hepatocellular antigens, which functionally act as a secondary lymphoid organ for CD8+ T cell priming.

    “These results proved that circulating T 458 cells have full access to hepatocellular antigens, which functionally act as a secondary 459 lymphoid organ for CD8+ T cell priming(93-95).”

    From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [93]

    The Discussion reports that naïve CD8+ T cells can be primed in the liver and that its endothelial barrier permits blood-borne cells to contact parenchymal cells. But it does not establish that circulating T cells have full access to hepatocellular antigens or that the liver functions generally as a secondary lymphoid organ; it says the antigen-presenting cell was not identified and predicts that this activation is restricted to MHC class I-restricted T cells. Page numbers were not supplied for these passages. (LLM, conf=0.86)

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  • Prior studies have provided evidence for priming of CD8+ T cells within the liver.

    “Prior studies have provided evidence for priming of CD8+ T cells within the liver.39,40,68,69”

    From TLR9-independent CD8+ T cell responses in hepatic AAV gene transfer through IL-1R1-MyD88 signaling (2024) · cites this paper as [68]

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Authors
Bertolino, P., Bowen, D. G., McCaughan, G. W., & Fazekas de St. Groth, B.
Affiliations
  • Centenary Institute (AU)
  • Centenary Institute of Cancer Medicine and Cell Biology , Newtown ,
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2001-05-01
Volume
166
Issue
9
Pages
5430-5438
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.166.9.5430
OpenAlex
W2141770821
Cited by
209
References
47
Citations by year
2026: 3 · 2025: 6 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 10 · 2014: 11 · 2013: 15 · 2012: 8
FWCI
2.05
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Sydney
  • Medical Research Council
  • National Health and Medical Research Council
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
Keywords
CD8+ T cells, liver, antigen-specific T cell activation, H-2Kb, viral hepatitis, T cell division
MeSH terms
Animals, Antigens, Differentiation, T-Lymphocyte, Autoantigens, Cell Division, Cell Movement, H-2 Antigens, Interphase, Liver, Lymph Nodes, Lymphocyte Activation, Metallothionein, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, T-Cell, Time Factors, Apoptosis, Lymphocyte Transfusion, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Adoptive Transfer, Mice

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