Source:http://linkedlifedata.com/resource/pubmed/id/18922914
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rdf:type | |
lifeskim:mentions |
umls-concept:C0003320,
umls-concept:C0024204,
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0205263,
umls-concept:C0439851,
umls-concept:C0449450,
umls-concept:C1179480,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1511636,
umls-concept:C1552596,
umls-concept:C1706438,
umls-concept:C1947931,
umls-concept:C2698600
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pubmed:issue |
20
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pubmed:dateCreated |
2008-10-16
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pubmed:abstractText |
Encounter of self-antigens in the periphery by mature T cells induces tolerance in the steady-state. Hence, it is not understood why the same peripheral antigens are also promiscuously expressed in the thymus to mediate central tolerance. Here, we analyzed CD8(+) T-cell tolerance to such an antigen constituted by ovalbumin under the control of the tyrosinase promoter. As expected, endogenous CD8(+) T-cell responses were altered in the periphery of transgenic mice, resulting from promiscuous expression of the self-antigen in mature medullary epithelial cells and deletion of high-affinity T cells in the thymus. In adoptive T-cell transfer experiments, we observed constitutive presentation of the self-antigen in peripheral lymph nodes. Notably, this self-antigen presentation induced persisting cytotoxic cells from high-affinity CD8(+) T-cell precursors. Lymph node resident melanoblasts expressing tyrosinase directly presented the self-antigen to CD8(+) T cells, independently of bone marrow-derived antigen-presenting cells. This peripheral priming was independent of the subcellular localization of the self-antigen, indicating that this mechanism may apply to other melanocyte-associated antigens. Hence, central tolerance by promiscuous expression of peripheral antigens is a mandatory, rather than a superfluous, mechanism to counteract the peripheral priming, at least for self-antigens that can be directly presented in lymph nodes. The peripheral priming by lymph node melanoblasts identified here may constitute an advantage for immunotherapies based on adoptive T-cell transfer.
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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 |
Oct
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pubmed:issn |
1538-7445
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
68
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8410-8
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pubmed:meshHeading |
pubmed-meshheading:18922914-Animals,
pubmed-meshheading:18922914-Antigen Presentation,
pubmed-meshheading:18922914-Autoantigens,
pubmed-meshheading:18922914-Immunotherapy,
pubmed-meshheading:18922914-Lymph Nodes,
pubmed-meshheading:18922914-Melanocytes,
pubmed-meshheading:18922914-Melanoma,
pubmed-meshheading:18922914-Mice,
pubmed-meshheading:18922914-Mice, Inbred C57BL,
pubmed-meshheading:18922914-Mice, Inbred DBA,
pubmed-meshheading:18922914-Ovalbumin,
pubmed-meshheading:18922914-T-Lymphocytes, Cytotoxic
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pubmed:year |
2008
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pubmed:articleTitle |
Direct presentation of a melanocyte-associated antigen in peripheral lymph nodes induces cytotoxic CD8+ T cells.
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pubmed:affiliation |
Department of Dermatology, Louis Jeantet Laboratory, Skin Cancers, University Medical Center, Geneva, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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