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Soluble N-Acetylgalactosamine-Modified Antigens Enhance Hepatocyte-Dependent Antigen Cross-Presentation and Result in Antigen-Specific CD8+ T Cell Tolerance Development
- Source :
- Frontiers in Immunology, Frontiers in Immunology, Vol 12 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- Hepatocytes compose up to 80% of the total liver and have been indicated as important players in the induction of immunologic tolerance in this organ. We show that hepatocytes possess the molecular machinery required for the cross-presentation of extracellular antigens. Using a derivative of the model antigen ovalbumin (OVA) covalently modified with a polymer containing multiple N-acetylgalactosamine residues (pGal-OVA) that enhance extracellular antigen uptake by mimicking the glycome of apoptotic debris, we show efficient hepatocyte-dependent induction of cross-tolerance of both adoptively transferred OT-I cells and endogenous OVA-specific CD8+ T lymphocytes, for example inducing tolerance to OVA-expressing skin transplants. Our study confirms that hepatocytes are capable of inducing peripheral tolerogenesis and provides proof of concept that they may be a valuable candidate for in vivo targeted tolerogenic treatments.
- Subjects :
- lcsh:Immunologic diseases. Allergy
Acetylgalactosamine
Ovalbumin
Immunology
Vesicular Transport Proteins
Mice, Transgenic
CD8-Positive T-Lymphocytes
Cross-Priming
Antigen
medicine
Extracellular
Immune Tolerance
Immunology and Allergy
Cytotoxic T cell
Animals
ATP Binding Cassette Transporter, Subfamily B, Member 2
Antigens
priming
Immunologic Tolerance
Cells, Cultured
cross-presentation
Original Research
Mice, Knockout
Antigen Presentation
antigen modifications
tolerance
cross-presentation/priming
biology
Chemistry
Cross-presentation
Skin Transplantation
Adoptive Transfer
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
Solubility
CD8 T cell
Hepatocyte
biology.protein
hepatocytes
lcsh:RC581-607
CD8
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....a35ac58bbcf71a5f64c170acf103d92d