PMID- 17576158
OWN - NLM
STAT- MEDLINE
DCOM- 20070807
LR  - 20091119
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 18
IP  - 6
DP  - 2007 Jun
TI  - Activation of immature monocyte-derived dendritic cells after transduction with 
      high doses of lentiviral vectors.
PG  - 536-46
AB  - Dendritic cells (DCs) are an attractive tool for immunomodulation, targeting 
      mature DCs (mDCs) for immunization or immature/semimature DCs (iDCs) for 
      tolerization. Therefore, introducing antigens into DCs has become a prime topic 
      in various immunological disciplines. Numerous studies have shown that 
      lentiviruses are an efficient vehicle for this purpose. This study evaluates the 
      effects of lentiviral transduction on iDC activation. Immature DCs are 
      efficiently transduced with increasing doses of lentivirus without affecting cell 
      viability. Transduction at low multiplicities of infection (MOIs) did not result 
      in phenotypical or functional maturation. Higher doses of lentivirus, however, 
      resulted in upregulation of adhesion, costimulatory, and HLA molecules, as well 
      as in increased allostimulatory capacity and secretion of interleukin (IL)-6, 
      IL-8, and tumor necrosis factor-alpha. Production of IL-12 p70, IL-10, and 
      interferon-alpha was observed only at extremely high doses. Protein kinase R 
      phosphorylation on transduction at an MOI of 150 was demonstrated by Western 
      blotting. A Toll-like receptor (TLR)-driven luciferase reporter assay showed 
      dose-dependent activation of TLR2, TLR3, and TLR8, which was independent of the 
      pseudotype, production, or transduction protocol and was abrogated on heat 
      inactivation. These data show that lentiviral vectors provide not only the 
      antigen but also appropriate activation signals to iDCs, favoring their use for 
      immunotherapy and vaccine development.
FAU - Breckpot, Karine
AU  - Breckpot K
AD  - Laboratory of Molecular and Cellular Therapy, Department of Physiology and 
      Immunology, Medical School of Vrije Universiteit Brussel, 1090 Brussels, Belgium. 
      karine.breckpot@vub.ac.be
FAU - Emeagi, Perpetua
AU  - Emeagi P
FAU - Dullaers, Melissa
AU  - Dullaers M
FAU - Michiels, Annelies
AU  - Michiels A
FAU - Heirman, Carlo
AU  - Heirman C
FAU - Thielemans, Kris
AU  - Thielemans K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Cytokines)
RN  - 0 (Toll-Like Receptors)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
SB  - IM
MH  - Cell Adhesion
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology
MH  - Flow Cytometry
MH  - *Gene Transfer Techniques
MH  - Genetic Vectors
MH  - Humans
MH  - Lentivirus/*genetics
MH  - Monocytes/*immunology
MH  - Phenotype
MH  - Toll-Like Receptors/genetics/metabolism
MH  - *Transduction, Genetic
MH  - eIF-2 Kinase/genetics/metabolism
EDAT- 2007/06/20 09:00
MHDA- 2007/08/08 09:00
CRDT- 2007/06/20 09:00
PHST- 2007/06/20 09:00 [pubmed]
PHST- 2007/08/08 09:00 [medline]
PHST- 2007/06/20 09:00 [entrez]
AID - 10.1089/hum.2007.006 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2007 Jun;18(6):536-46. doi: 10.1089/hum.2007.006.