Source:http://linkedlifedata.com/resource/pubmed/id/15383561
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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0003320,
umls-concept:C0021853,
umls-concept:C0026724,
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0205263,
umls-concept:C0221908,
umls-concept:C1155266,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1704410,
umls-concept:C1706438,
umls-concept:C1879547,
umls-concept:C2698600
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pubmed:issue |
7
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pubmed:dateCreated |
2004-9-22
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pubmed:abstractText |
Intestinal autoimmune diseases are thought to be associated with a breakdown in tolerance, leading to mucosal lymphocyte activation perhaps as a result of encounter with bacterium-derived Ag. To study mucosal CD8(+) T cell activation, tolerance, and polarization of autoimmune reactivity to self-Ag, we developed a novel (Fabpl(4x at -132)-OVA) transgenic mouse model expressing a truncated form of OVA in intestinal epithelia of the terminal ileum and colon. We found that OVA-specific CD8(+) T cells were partially tolerant to intestinal epithelium-derived OVA, because oral infection with Listeria monocytogenes-encoding OVA did not elicit an endogenous OVA-specific MHC class I tetramer(+)CD8(+) T cell response and IFN-gamma-, IL-4-, and IL-5-secreting T cells were decreased in the Peyer's patches, mesenteric lymph nodes, and intestinal mucosa of transgenic mice. Adoptive transfer of OVA-specific CD8(+) (OT-I) T cells resulted in their preferential expansion in the Peyer's patches and mesenteric lymph nodes and subsequently in the epithelia and lamina propria but failed to cause mucosal inflammation. Thus, CFSE-labeled OT-I cells greatly proliferated in these tissues by 5 days posttransfer. Strikingly, OT-I cell-transferred Fabpl(4x at -132)-OVA transgenic mice underwent a transient weight loss and developed a CD8(+) T cell-mediated acute enterocolitis 5 days after oral L. monocytogenes-encoding OVA infection. These findings indicate that intestinal epithelium-derived "self-Ag" gains access to the mucosal immune system, leading to Ag-specific T cell activation and clonal deletion. However, when Ag is presented in the context of bacterial infection, the associated inflammatory signals drive Ag-specific CD8(+) T cells to mediate intestinal immunopathology.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Autoantigens,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acid-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ovalbumin
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
173
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4324-30
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15383561-Acute Disease,
pubmed-meshheading:15383561-Administration, Oral,
pubmed-meshheading:15383561-Adoptive Transfer,
pubmed-meshheading:15383561-Amino Acid Sequence,
pubmed-meshheading:15383561-Animals,
pubmed-meshheading:15383561-Autoantigens,
pubmed-meshheading:15383561-CD8-Positive T-Lymphocytes,
pubmed-meshheading:15383561-Carrier Proteins,
pubmed-meshheading:15383561-Cell Differentiation,
pubmed-meshheading:15383561-Cell Line,
pubmed-meshheading:15383561-Cell Movement,
pubmed-meshheading:15383561-Cells, Cultured,
pubmed-meshheading:15383561-Enterocolitis,
pubmed-meshheading:15383561-Epitopes, T-Lymphocyte,
pubmed-meshheading:15383561-Fatty Acid-Binding Proteins,
pubmed-meshheading:15383561-Humans,
pubmed-meshheading:15383561-Immune Tolerance,
pubmed-meshheading:15383561-Immunity, Mucosal,
pubmed-meshheading:15383561-Intestinal Mucosa,
pubmed-meshheading:15383561-Listeria monocytogenes,
pubmed-meshheading:15383561-Listeriosis,
pubmed-meshheading:15383561-Lymph Nodes,
pubmed-meshheading:15383561-Lymphocyte Activation,
pubmed-meshheading:15383561-Mesentery,
pubmed-meshheading:15383561-Mice,
pubmed-meshheading:15383561-Mice, Inbred C57BL,
pubmed-meshheading:15383561-Mice, Transgenic,
pubmed-meshheading:15383561-Molecular Sequence Data,
pubmed-meshheading:15383561-Ovalbumin,
pubmed-meshheading:15383561-Peyer's Patches
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pubmed:year |
2004
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pubmed:articleTitle |
Intestinal epithelial antigen induces mucosal CD8 T cell tolerance, activation, and inflammatory response.
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pubmed:affiliation |
Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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