Cited by 316T-cell and B-cell ImmunologyLiver physiology and pathologyLiver Diseases and Immunity

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The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity

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Bowen, David G., Zen, Monica, Holz, Lauren, Davis, Thomas, McCaughan, Geoffrey W., Bertolino, Patrick·2004·Journal of Clinical Investigation

DOI 10.1172/jci21593PMC PMC514586

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Abstract

Hepatic immunobiology is paradoxical: although the liver possesses unusual tolerogenic properties, it is also the site of effective immune responses against multiple pathogens and subject to immune-mediated pathology. The mechanisms underlying this dichotomy remain unclear. Following previous work demonstrating that the liver may act as a site of primary T cell activation, we demonstrate here that the balance between immunity and tolerance in this organ is established by competition for primary activation of CD8+ T cells between the liver and secondary lymphoid tissues, with the immune outcome determined by the initial site of activation. Using a transgenic mouse model in which antigen is expressed within both liver and lymph nodes, we show that while naive CD8+ T cells activated within the lymph nodes were capable of mediating hepatitis, cells undergoing primary activation within the liver exhibited defective cytotoxic function and shortened half-life and did not mediate hepatocellular injury. The implications of these novel findings may pertain not only to the normal maintenance of peripheral tolerance, but also to hepatic allograft tolerance and the immunopathogenesis of chronic viral hepatitis.

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The role of CLEVER-1 in lymphocyte recruitment to the human liver
Shetty, S. (2011) · University of Birmingham Institutional Research Archive (University of Birmingham)
Immunology of Liver
Tian, Z., & Chen, Y. (2012) · Springer eBooks · doi:10.1007/978-3-642-28702-2_8

Authors: Bowen, D. G., Zen, M., Holz, L., Davis, T., McCaughan, G. W., & Bertolino, P.
Affiliations: Centenary Institute (AU)
ORCID: Bowen, David G.
Zen, Monica
Holz, Lauren
McCaughan, Geoffrey W.
Bertolino, Patrick
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2004-09-01
Volume: 114
Issue: 5
Pages: 701-712
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci21593
PMC: PMC514586
OpenAlex: W1968141301
Cited by: 316
References: 53
Citations by year: 2026: 3 · 2025: 2 · 2024: 5 · 2023: 8 · 2022: 7 · 2021: 11 · 2020: 11 · 2019: 12 · 2018: 11 · 2017: 14 · 2016: 15 · 2015: 14 · 2014: 18 · 2013: 27 · 2012: 23
FWCI: 6.14
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Children’s Hospital of Wisconsin Research Institute
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 › Hepatology › Liver Diseases and Immunity
Keywords: liver, CD8+ T cells, peripheral tolerance, secondary lymphoid organs, hepatitis, cytotoxic function, chronic viral hepatitis, transgenic mouse model
MeSH terms: Adjuvants, Immunologic, Animals, Antibodies, Monoclonal, Hepatitis, Immune Tolerance, Liver, Lymph Nodes, T-Lymphocytes, CD8-Positive T-Lymphocytes, L-Selectin, Mice

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The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity

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