Cross‐presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 T cell tolerance
Open accessAbstract
After ingestion, oral antigens distribute systemically and provoke T cell stimulation outside the gastrointestinal tract. Within the liver, scavenger liver sinusoidal endothelial cells (LSEC) eliminate blood‐borne antigens and induce T cell tolerance. Here we investigated whether LSEC contribute to oral tolerance. Oral antigens were efficiently cross‐presented on H‐2K b by LSEC to naive CD8 T cells. Cross‐presentation efficiency in LSEC but not dendritic cells was increased by antigen‐exposure to heat or low pH. Mechanistically, cross‐presentation in LSEC requires endosomal maturation, involves hsc73 and proteasomal degradation. H‐2K b‐restricted cross‐presentation of oral antigens by LSEC in vivo induced CD8 T cell priming and led to development of CD8 T cell tolerance in two independent experimental systems. Adoptive transfer of LSEC from mice fed with antigen (ovalbumin) into RAG2–/– knockout mice, previously reconstituted with naive ovalbumin‐specific CD8 T cells, prevented development of specific cytotoxicity and expression of IFN‐γ in CD8 T cells. Using a new transgenic mouse line expressing H‐2K b only on endothelial cells, we have demonstrated that oral antigen administration leads to tolerance in H‐2K b‐restricted CD8 T cells. Collectively, our data demonstrate a participation of the liver, in particular scavenger LSEC, in development of CD8 T cell tolerance towards oral antigens.
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Hepatic infiltration by CD4+ T, CD8+ T and B lymphocytes is evident in different experimental models of MASH.
“Hepatic infiltration by CD4+ T, CD8+ T and B lymphocytes is evident in different experimental models of MASH (28-30), while Rag1 -/mice which lack mature T and B cells are protected from lobular inflammation and liver cell injury induced by feeding a cholinedeficient high fat diet (28).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [30]
The Introduction (page unavailable) discusses liver sinusoidal endothelial cells presenting antigens to CD4 and CD8 T cells, and the section on LSEC cross-tolerizing CD8 T cells (page unavailable) reports tolerance after oral antigen exposure. Searches for MASH, steatohepatitis, and hepatic lymphocyte infiltration found no passage addressing infiltration by CD4, CD8, and B cells in experimental MASH models. (LLM, conf=0.76)
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- Authors
- Limmer, A., Ohl, J., Wingender, G., Berg, M., Jüngerkes, F., Schumak, B., Djandji, D., Scholz, K., Klevenz, A., Hegenbarth, S., Momburg, F., Hämmerling, G. J., Arnold, B., & Knolle, P. A.
- Affiliations
- University of Bonn (DE)
- German Cancer Research Center (DE)
- Corresponding author
- Limmer, Andreas
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2005-10
- Volume
- 35
- Issue
- 10
- Pages
- 2970-2981
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2127036601
- Cited by
- 169
- References
- 59
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 8 · 2023: 7 · 2022: 8 · 2021: 13 · 2020: 12 · 2019: 7 · 2018: 6 · 2017: 7 · 2016: 4 · 2015: 8 · 2014: 5 · 2013: 9 · 2012: 5
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Volkswagen Foundation
- Rheinische Friedrich-Wilhelms-Universität Bonn
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- oral tolerance, liver sinusoidal endothelial cells, cross-presentation, CD8+ T cell tolerance, oral antigen, H-2Kb, endosomal maturation, Hsc70, proteasomal degradation, ovalbumin, adoptive transfer, interferon-gamma
- MeSH terms
- Animals, Antigens, Immune Tolerance, Liver, Antigen Presentation, Mice, Knockout, CD8-Positive T-Lymphocytes, Adoptive Transfer, Endothelial Cells, Cross-Priming, Mice
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