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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2006-9-20
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pubmed:abstractText |
Dendritic cell (DC) presentation of self antigen to thymocytes is essential to the establishment of central tolerance. We show here that circulating DCs were recruited to the thymic medulla through a three-step adhesion cascade involving P-selectin, interactions of the integrin VLA-4 with its ligand VCAM-1, and pertussis toxin-sensitive chemoattractant signaling. Ovalbumin-specific OT-II thymocytes were selectively deleted after intravenous injection of antigen-loaded exogenous DCs. We documented migration of endogenous DCs to the thymus in parabiotic mice and after painting mouse skin with fluorescein isothiocyanate. Antibody to VLA-4 blocked the accumulation of peripheral tissue-derived DCs in the thymus and also inhibited the deletion of OT-II thymocytes in mice expressing membrane-bound ovalbumin in cardiac myocytes. These findings identify a migratory route by which peripheral DCs may contribute to central tolerance.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1529-2908
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1092-100
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16951687-Animals,
pubmed-meshheading:16951687-Antigen Presentation,
pubmed-meshheading:16951687-Antigens, CD4,
pubmed-meshheading:16951687-Cell Movement,
pubmed-meshheading:16951687-Clonal Deletion,
pubmed-meshheading:16951687-Dendritic Cells,
pubmed-meshheading:16951687-Integrin alpha4beta1,
pubmed-meshheading:16951687-Interleukin-2 Receptor alpha Subunit,
pubmed-meshheading:16951687-Mice,
pubmed-meshheading:16951687-Mice, Inbred C57BL,
pubmed-meshheading:16951687-Ovalbumin,
pubmed-meshheading:16951687-P-Selectin,
pubmed-meshheading:16951687-T-Lymphocytes,
pubmed-meshheading:16951687-T-Lymphocytes, Regulatory,
pubmed-meshheading:16951687-Thymus Gland,
pubmed-meshheading:16951687-Vascular Cell Adhesion Molecule-1
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pubmed:year |
2006
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pubmed:articleTitle |
Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus.
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pubmed:affiliation |
The CBR Institute for Biomedical Research, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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