Source:http://linkedlifedata.com/resource/pubmed/id/18566407
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2008-6-20
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| pubmed:abstractText |
Skeletal muscles account for more than 30% of the human body, yet mechanisms of immunological tolerance to this tissue remain mainly unexplored. To investigate the mechanisms of tolerance to muscle-specific proteins, we generated transgenic mice expressing the neo-autoantigen OVA exclusively in skeletal muscle (SM-OVA mice). SM-OVA mice were bred with OT-I or OT-II mice that possess a transgenic TCR specific for OVA peptides presented by MHC class I or class II, respectively. Tolerance to OVA did not involve clonal deletion, anergy or an increased regulatory T cell compartment. Rather, CD4+ T cell tolerance resulted from a mechanism of ignorance revealed by their response following OVA immunization. In marked contrast, CD8+ T cells exhibited a loss of OVA-specific cytotoxic activity associated with up-regulation of the immunoregulatory programmed death-1 molecule. Adoptive transfer experiments further showed that OVA expression in skeletal muscle was required to maintain this functional tolerance. These results establish a novel asymmetric model of immunological tolerance to muscle autoantigens involving Ag ignorance for CD4+ T cells, whereas muscle autoantigens recognized by CD8+ T cells results in blockade of their cytotoxic function. These observations may be helpful for understanding the breakage of tolerance in autoimmune muscle diseases.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ovalbumin,
http://linkedlifedata.com/resource/pubmed/chemical/PD-1 antigen, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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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 |
181
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
408-17
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| pubmed:meshHeading |
pubmed-meshheading:18566407-Animals,
pubmed-meshheading:18566407-Antigens,
pubmed-meshheading:18566407-Antigens, Differentiation,
pubmed-meshheading:18566407-CD4-Positive T-Lymphocytes,
pubmed-meshheading:18566407-CD8-Positive T-Lymphocytes,
pubmed-meshheading:18566407-Cells, Cultured,
pubmed-meshheading:18566407-Chickens,
pubmed-meshheading:18566407-Forkhead Transcription Factors,
pubmed-meshheading:18566407-Gene Expression,
pubmed-meshheading:18566407-Immune Tolerance,
pubmed-meshheading:18566407-Mice,
pubmed-meshheading:18566407-Mice, Inbred C57BL,
pubmed-meshheading:18566407-Mice, Transgenic,
pubmed-meshheading:18566407-Muscle, Skeletal,
pubmed-meshheading:18566407-Ovalbumin,
pubmed-meshheading:18566407-Receptors, Antigen, T-Cell,
pubmed-meshheading:18566407-Transgenes,
pubmed-meshheading:18566407-Up-Regulation
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| pubmed:year |
2008
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| pubmed:articleTitle |
Functional tolerance of CD8+ T cells induced by muscle-specific antigen expression.
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| pubmed:affiliation |
Institut National de la Santé et de la Recherche Médicale, Unité 905, University of Rouen, and Department of Immunology, Rouen University Hospital, Rouen, France. sebastien.calbo@univ-rouen.fr
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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