PMID- 15647325
OWN - NLM
STAT- MEDLINE
DCOM- 20050524
LR  - 20071115
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 77
IP  - 4
DP  - 2005 Apr
TI  - MHC class II signaling function is regulated during maturation of plasmacytoid 
      dendritic cells.
PG  - 560-7
AB  - 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.
FAU - Drenou, Bernard
AU  - Drenou B
AD  - Laboratoire d'Hematologie et de Biologie des Cellules Sanguines (UPRES 22-33), 
      Faculte de Medicine, Rennes, Cedex, France.
FAU - Amiot, Laurence
AU  - Amiot L
FAU - Setterblad, Niclas
AU  - Setterblad N
FAU - Taque, Sophie
AU  - Taque S
FAU - Guilloux, Valerie
AU  - Guilloux V
FAU - Charron, Dominique
AU  - Charron D
FAU - Fauchet, Renee
AU  - Fauchet R
FAU - Mooney, Nuala
AU  - Mooney N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050112
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (HLA-DR Antigens)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Apoptosis/immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology/physiology
MH  - Enzyme Activation
MH  - HLA-DR Antigens/analysis/*physiology
MH  - Humans
MH  - Membrane Microdomains/immunology
MH  - Plasma Cells/immunology
MH  - Protein Kinase C/metabolism
MH  - Signal Transduction/*immunology
EDAT- 2005/01/14 09:00
MHDA- 2005/05/25 09:00
CRDT- 2005/01/14 09:00
PHST- 2005/01/14 09:00 [pubmed]
PHST- 2005/05/25 09:00 [medline]
PHST- 2005/01/14 09:00 [entrez]
AID - jlb.0704423 [pii]
AID - 10.1189/jlb.0704423 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2005 Apr;77(4):560-7. doi: 10.1189/jlb.0704423. Epub 2005 Jan 12.