Mhc Class Ii–Expressing Hepatocytes Function As Antigen–Presenting Cells and Activate Specific Cd4 T Lymphocyutes
Open accessAbstract
The ability to activate CD4 T cells is restricted to antigen–presenting cells that express major histocompatibility complex (MHC) class II molecules. Parenchymal cells normally do not express MHC class II molecules; however, in clinical hepatitis, viral or autoimmune, hepatocytes often exhibit aberrant MHC class II expression. It is not known whether MHC class II–expressing hepatocytes can function as antigen–presenting cells, but it has been suggested that aberrant MHC class II expression by parenchymal cells may cause autoimmune disease. Therefore, we generated transgenic mice that specifically overexpress class II transactivator molecules in hepatocytes. Hepatocytes from these mice exhibited stable MHC class II expression and were used to stimulate CD4 T cells from T–cell receptor transgenic mice and CD4 T–cell lines. MHC II–expressing hepatocytes featured costimulatory CD80 molecules and could serve as antigen–presenting cells that were able to process protein antigen and to activate specific CD4 T cells. Nevertheless, the transgenic mice with aberrant hepatocellular MHC class II expression did not exhibit any symptoms of autoimmune disease. In conclusion, MHC II–expressing hepatocytes, as found in clinical hepatitis, can present antigen and activate CD4 T cells. The ability of hepatocytes to present antigen on MHC II molecules does not seem to be a sufficient cause for inflammatory autoimmunity and hepatitis. However, we still need to explore whether such antigen presentation is occurring in vivo . The transgenic mice described in this study may serve as a model to study the immune interaction of hepatocytes and CD4 T cells in both in vitro and in vivo .
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MHC class II antigen presentation by hepatocytes cannot trigger effective activation of T cells, and in turn might favour a chronic viral infection over viral clearance.
“This evidence suggests that the fate of MHC class II antigen presentation by the hepatocyte cannot trigger an effective activation of the T cells, and in turn it might favour a chronic viral infection over viral clearance(31, 39-41).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [40]
The Abstract reports that MHC class II-expressing hepatocytes activated specific CD4 T cells, contrary to the claim that they cannot trigger T-cell activation. The Discussion says their effect on viral clearance versus persistence remains to be determined; it does not establish that hepatocyte presentation favors chronic infection. Page numbers are not available in our copy. (LLM, conf=0.89)
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Experimental — accuracy not yet measuredConstitutive expression of MHC class II on hepatocytes in murine models of choriomeningitis virus infection increases the duration of the infection and reduces production of pro-inflammatory cytokines (IFN-γ) by virus-specific CD4+ and CD8+ T cells.
“Constitutive expression of MHC class II on hepatocytes in murine models of choriomeningitis virus infection has shown to increase the duration of the infection, reducing the production of pro-inflammatory cytokines (i.e. IFN-γ) by virus-specific CD4 + T and CD8 + T cells.”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [40]
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Experimental — accuracy not yet measuredA sizeable proportion, between 23% and 48%, of patients with MASLD and/or MASH were found to exhibit signs of AIH and/or PBC, including interface hepatitis and generation of anti-nuclear or anti-mitochondrial antibodies.
“In the small number of investigations performed, a sizeable proportion (between 23% and 48%) of patients with MASLD and/or MASH were found to exhibit signs of AIH and/or PBC, including interface hepatitis and generation of anti-nuclear (ANA) or anti-mitochondrial (AMA) antibodies (38-40).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [40]
The Results and Discussion (page unavailable) describe experiments in CIITA-transgenic mice and mention autoimmune hepatitis, but do not report findings in patients with MASLD or MASH. Searches for the 23%–48% range, interface hepatitis, and ANA or AMA found no passage addressing the claimed patient findings. (LLM, conf=0.78)
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- Authors
- Herkel, J., Jagemann, B., Wiegard, C., Lazaro, J. F. G., Lueth, S., Kanzler, S., Blessing, M., Schmitt, E., & Lohse, A. W.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Lohse, Ansgar W.
- Venue
- Hepatology
- Published
- 2003-05
- Volume
- 37
- Issue
- 5
- Pages
- 1079-1085
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W1987116953
- Cited by
- 164
- References
- 47
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 10 · 2023: 7 · 2022: 6 · 2021: 13 · 2020: 8 · 2019: 12 · 2018: 5 · 2017: 12 · 2016: 2 · 2015: 8 · 2014: 11 · 2013: 4 · 2012: 6
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 490)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- MHC class II, hepatocytes, antigen-presenting cells, CD4+ T cell activation, CIITA, transgenic mice, hepatitis, autoimmune disease, antigen processing
- MeSH terms
- Animals, Antigen-Presenting Cells, Histocompatibility Antigens Class II, Hepatitis, Lymphocyte Activation, Mice, Inbred Strains, Mice, Transgenic, Nuclear Proteins, CD4-Positive T-Lymphocytes, Trans-Activators, Gene Expression, Hepatocytes, Mice
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