Source:http://linkedlifedata.com/resource/pubmed/id/19205034
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2009-5-4
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pubmed:abstractText |
Peripheral CD8 T-cell tolerance can be generated outside lymphatic tissue in the liver, but the course of events leading to tolerogenic interaction of hepatic cell populations with circulating T-cells remain largely undefined. Here we demonstrate that preferential uptake of systemically circulating antigen by murine liver sinusoidal endothelial cells (LSECs), and not by other antigen-presenting cells in the liver or spleen, leads to cross-presentation on major histocompatibility complex (MHC) I molecules, which causes rapid antigen-specific naïve CD8 T-cell retention in the liver but not in other organs. Using bone-marrow chimeras and a novel transgenic mouse model (Tie2-H-2K(b) mice) with endothelial cell-specific MHC I expression, we provide evidence that cross-presentation by organ-resident and radiation-resistant LSECs in vivo was both essential and sufficient to cause antigen-specific retention of naïve CD8 T-cells under noninflammatory conditions. This was followed by sustained CD8 T-cell proliferation and expansion in vivo, but ultimately led to the development of T-cell tolerance. Conclusion: Our results show that cross-presentation of circulating antigens by LSECs caused antigen-specific retention of naïve CD8 T-cells and identify antigen-specific T-cell adhesion as the first step in the induction of T-cell tolerance.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1527-3350
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
49
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1664-72
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pubmed:meshHeading |
pubmed-meshheading:19205034-Animals,
pubmed-meshheading:19205034-Antigen Presentation,
pubmed-meshheading:19205034-Antigens,
pubmed-meshheading:19205034-CD8-Positive T-Lymphocytes,
pubmed-meshheading:19205034-Cell Migration Inhibition,
pubmed-meshheading:19205034-Cells, Cultured,
pubmed-meshheading:19205034-Cross-Priming,
pubmed-meshheading:19205034-Endothelial Cells,
pubmed-meshheading:19205034-Immune Tolerance,
pubmed-meshheading:19205034-Liver,
pubmed-meshheading:19205034-Mice,
pubmed-meshheading:19205034-Mice, Inbred C57BL,
pubmed-meshheading:19205034-Mice, Transgenic,
pubmed-meshheading:19205034-Ovalbumin
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pubmed:year |
2009
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pubmed:articleTitle |
Systemic antigen cross-presented by liver sinusoidal endothelial cells induces liver-specific CD8 T-cell retention and tolerization.
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pubmed:affiliation |
Institute of Molecular Medicine and Experimental Immunology, University Hospital Aachen, Aachen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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