Source:http://linkedlifedata.com/resource/pubmed/id/15647325
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2005-3-28
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pubmed:abstractText |
Dendritic cells (DC) play a central role in the immune response, linking innate and adaptative responses to pathogens. Myeloid DC (MDC) produce interleukin-12 in response to bacterial stimuli, whereas plasmacytoid DC (PDC) produce high levels of type I interferon upon viral infection. Human leukocyte antigen (HLA)-DR engagement has been shown to induce apoptosis in various antigen-presenting cells (APC). We now report the consequences of HLA-DR molecule engagement in human PDC, which had thus far not been studied as a result of the difficulty in isolating such cells. HLA-DR engagement on PDC, obtained using a two-step, immunomagnetic separation, led to recruitment of HLA-DR molecules at the site of engagement in mature but not immature PDC. In contrast, relocalization of protein kinase C (PKC) isoenzymes, indicating PKC activation, was observed at the site of HLA-DR engagement and was accompanied by relocalization of a lipid raft marker, the ganglioside M1 staining, in immature and mature PDC. Similar to MDC, HLA-DR-mediated apoptosis was regulated throughout PDC maturation. Freshly isolated PDC were resistant, whereas CD40 ligand-matured PDC were sensitive to HLA-DR-mediated apoptosis. Neither caspase activation nor PKC activation was required for HLA-DR-mediated apoptosis. However, the intrinsic pathway of apoptosis was implicated as mature PDC underwent mitochondrial depolarization in response to HLA-DR engagement. These data provide further arguments for considering HLA-DR-mediated apoptosis as a conserved mechanism of regulating survival of diverse APC and support the ongoing development of humanized ligands for HLA class II molecules as therapeutic tools for use in lymphoproliferative disease.
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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 |
Apr
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pubmed:issn |
0741-5400
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
77
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
560-7
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15647325-Apoptosis,
pubmed-meshheading:15647325-Cells, Cultured,
pubmed-meshheading:15647325-Dendritic Cells,
pubmed-meshheading:15647325-Enzyme Activation,
pubmed-meshheading:15647325-HLA-DR Antigens,
pubmed-meshheading:15647325-Humans,
pubmed-meshheading:15647325-Membrane Microdomains,
pubmed-meshheading:15647325-Plasma Cells,
pubmed-meshheading:15647325-Protein Kinase C,
pubmed-meshheading:15647325-Signal Transduction
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pubmed:year |
2005
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pubmed:articleTitle |
MHC class II signaling function is regulated during maturation of plasmacytoid dendritic cells.
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pubmed:affiliation |
Laboratoire d'Hématologie et de Biologie des Cellules Sanguines (UPRES 22-33), Faculté de Médicine, Rennes, Cedex, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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