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Activation of immature monocyte-derived dendritic cells after transduction with high doses of lentiviral vectors

Karine Breckpot, Perpetua Emeagi, Melissa Dullaers UGent, Annelies Michiels, Carlo Heirman and Kris Thielemans (2007) HUMAN GENE THERAPY. 18(6). p.536-546
abstract
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-a. Production of IL-12 p70, IL-10, and interferon-a 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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
MATURATION, INDUCTION, RESPONSES, VIRAL-INFECTION, IN-VIVO, THERAPEUTIC ANTITUMOR IMMUNITY, EFFICIENT GENE-TRANSFER, TOLERANCE, IMMUNOTHERAPY, MACROPHAGES
journal title
HUMAN GENE THERAPY
Hum. Gene Ther.
volume
18
issue
6
pages
536 - 546
Web of Science type
Article
Web of Science id
000247721600006
JCR category
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
JCR impact factor
4.33 (2007)
JCR rank
17/138 (2007)
JCR quartile
1 (2007)
ISSN
1043-0342
DOI
10.1089/hum.2007.006
language
English
UGent publication?
no
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1227893
handle
http://hdl.handle.net/1854/LU-1227893
date created
2011-05-20 09:24:53
date last changed
2016-12-19 15:44:49
@article{1227893,
  abstract     = {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-a. Production of IL-12 p70, IL-10, and interferon-a 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.},
  author       = {Breckpot, Karine and Emeagi, Perpetua and Dullaers, Melissa and Michiels, Annelies and Heirman, Carlo and Thielemans, Kris},
  issn         = {1043-0342},
  journal      = {HUMAN GENE THERAPY},
  keyword      = {MATURATION,INDUCTION,RESPONSES,VIRAL-INFECTION,IN-VIVO,THERAPEUTIC ANTITUMOR IMMUNITY,EFFICIENT GENE-TRANSFER,TOLERANCE,IMMUNOTHERAPY,MACROPHAGES},
  language     = {eng},
  number       = {6},
  pages        = {536--546},
  title        = {Activation of immature monocyte-derived dendritic cells after transduction with high doses of lentiviral vectors},
  url          = {http://dx.doi.org/10.1089/hum.2007.006},
  volume       = {18},
  year         = {2007},
}

Chicago
Breckpot, Karine, Perpetua Emeagi, Melissa Dullaers, Annelies Michiels, Carlo Heirman, and Kris Thielemans. 2007. “Activation of Immature Monocyte-derived Dendritic Cells After Transduction with High Doses of Lentiviral Vectors.” Human Gene Therapy 18 (6): 536–546.
APA
Breckpot, K., Emeagi, P., Dullaers, M., Michiels, A., Heirman, C., & Thielemans, K. (2007). Activation of immature monocyte-derived dendritic cells after transduction with high doses of lentiviral vectors. HUMAN GENE THERAPY, 18(6), 536–546.
Vancouver
1.
Breckpot K, Emeagi P, Dullaers M, Michiels A, Heirman C, Thielemans K. Activation of immature monocyte-derived dendritic cells after transduction with high doses of lentiviral vectors. HUMAN GENE THERAPY. 2007;18(6):536–46.
MLA
Breckpot, Karine, Perpetua Emeagi, Melissa Dullaers, et al. “Activation of Immature Monocyte-derived Dendritic Cells After Transduction with High Doses of Lentiviral Vectors.” HUMAN GENE THERAPY 18.6 (2007): 536–546. Print.