|
|
Previous Article | Table of Contents | Next Article 
Blood, 15 August 2000, Vol. 96, No. 4, pp. 1327-1333
GENE THERAPY
Dendritic cells transduced by multiply deleted HIV-1 vectors
exhibit normal phenotypes and functions and elicit an HIV-specific
cytotoxic T-lymphocyte response in vitro
Andreas Gruber,
June Kan-Mitchell,
Kelli L. Kuhen,
Tetsu Mukai, and
Flossie Wong-Staal
From the Departments of Medicine and Biology,
University of California, San Diego, CA; and Karmanos Cancer Institute,
Wayne State University, Detroit, MI.
Dendritic cells (DCs) genetically modified to continually express
and present antigens may be potent physiologic adjuvants for induction
of prophylactic or therapeutic immunity. We have previously shown that
an env and nef deleted HIV-1 vector
(HIV-1 EN) pseudotyped with VSV-G transduced monocyte-derived
macrophages as well as CD34+ precursors of DCs. Here we
extended these findings with HIV-1 EN to highly differentiated human
DCs derived in culture from circulating monocytes (DCs). In addition, a
new vector derived from HIV-1 EN but further deleted in its remaining
accessory genes vif, vpr, and vpu
(HIV-1 EN V3) was also tested. Both vectors efficiently
transduced DCs. Transduction of DCs did not significantly alter their
viability or their immunophenotype when compared with untransduced DCs.
Furthermore, the phagocytic potential of immature DCs, as well as their
ability to differentiate into mature DCs capable of stimulating T-cell
proliferation, was not affected. Finally, DCs transduced by the
HIV-1 EN vector were able to elicit a primary antiviral cytotoxic
T-cell response in autologous CD8 T cells. These results suggest that
HIV-1-based vectors expressing viral antigens may be useful for in
vivo active immunization as well as ex vivo priming of cytotoxic T
cells for adoptive T-cell therapy.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
B. A. Colleton, X.-L. Huang, N. M. Melhem, Z. Fan, L. Borowski, G. Rappocciolo, and C. R. Rinaldo
Primary Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Responses Induced by Myeloid Dendritic Cells
J. Virol.,
June 15, 2009;
83(12):
6288 - 6299.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F.-c. Lin, Y. Peng, L. A. Jones, P. H. Verardi, and T. D. Yilma
Incorporation of CD40 Ligand into the Envelope of Pseudotyped Single-Cycle Simian Immunodeficiency Viruses Enhances Immunogenicity
J. Virol.,
February 1, 2009;
83(3):
1216 - 1227.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Peng, F.-c. Lin, P. H. Verardi, L. A. Jones, M. B. McChesney, and T. D. Yilma
Pseudotyped Single-Cycle Simian Immunodeficiency Viruses Expressing Gamma Interferon Augment T-Cell Priming Responses In Vitro
J. Virol.,
March 1, 2007;
81(5):
2187 - 2195.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Pichlmair, S. S. Diebold, S. Gschmeissner, Y. Takeuchi, Y. Ikeda, M. K. Collins, and C. Reis e Sousa
Tubulovesicular Structures within Vesicular Stomatitis Virus G Protein-Pseudotyped Lentiviral Vector Preparations Carry DNA and Stimulate Antiviral Responses via Toll-Like Receptor 9
J. Virol.,
January 15, 2007;
81(2):
539 - 547.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Majumder, M. L. Janket, E. A. Schafer, K. Schaubert, X.-L. Huang, J. Kan-Mitchell, C. R. Rinaldo Jr., and V. Ayyavoo
Human Immunodeficiency Virus Type 1 Vpr Impairs Dendritic Cell Maturation and T-Cell Activation: Implications for Viral Immune Escape
J. Virol.,
July 1, 2005;
79(13):
7990 - 8003.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. H. Tan, S. C. Beutelspacher, S.-A. Xue, Y.-H. Wang, P. Mitchell, J. C. McAlister, D. F. P. Larkin, M. O. McClure, H. J. Stauss, M. A. Ritter, et al.
Modulation of human dendritic-cell function following transduction with viral vectors: implications for gene therapy
Blood,
May 15, 2005;
105(10):
3824 - 3832.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Zarei, S. Abraham, J.-F. Arrighi, O. Haller, T. Calzascia, P. R. Walker, T. M. Kundig, C. Hauser, and V. Piguet
Lentiviral Transduction of Dendritic Cells Confers Protective Antiviral Immunity In Vivo
J. Virol.,
July 15, 2004;
78(14):
7843 - 7845.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Kan-Mitchell, B. Bisikirska, F. Wong-Staal, K. L. Schaubert, M. Bajcz, and M. Bereta
The HIV-1 HLA-A2-SLYNTVATL Is a Help-Independent CTL Epitope
J. Immunol.,
May 1, 2004;
172(9):
5249 - 5261.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Breckpot, C. Heirman, C. De Greef, P. van der Bruggen, and K. Thielemans
Identification of New Antigenic Peptide Presented by HLA-Cw7 and Encoded by Several MAGE Genes Using Dendritic Cells Transduced with Lentiviruses
J. Immunol.,
February 15, 2004;
172(4):
2232 - 2237.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Palmowski, L. Lopes, Y. Ikeda, M. Salio, V. Cerundolo, and M. K. Collins
Intravenous Injection of a Lentiviral Vector Encoding NY-ESO-1 Induces an Effective CTL Response
J. Immunol.,
February 1, 2004;
172(3):
1582 - 1587.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Wang, M. Messerle, R. Sapinoro, K. Santos, P. K. Hocknell, X. Jin, and S. Dewhurst
Murine Cytomegalovirus Abortively Infects Human Dendritic Cells, Leading to Expression and Presentation of Virally Vectored Genes
J. Virol.,
July 1, 2003;
77(13):
7182 - 7192.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. VandenDriessche, L. Thorrez, L. Naldini, A. Follenzi, L. Moons, Z. Berneman, D. Collen, and M. K. L. Chuah
Lentiviral vectors containing the human immunodeficiency virus type-1 central polypurine tract can efficiently transduce nondividing hepatocytes and antigen-presenting cells in vivo
Blood,
July 18, 2002;
100(3):
813 - 822.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. S. von Bergwelt-Baildon, R. H. Vonderheide, B. Maecker, N. Hirano, K. S. Anderson, M. O. Butler, Z. Xia, W. Y. Zeng, K. W. Wucherpfennig, L. M. Nadler, et al.
Human primary and memory cytotoxic T lymphocyte responses are efficiently induced by means of CD40-activated B cells as antigen-presenting cells: potential for clinical application
Blood,
May 1, 2002;
99(9):
3319 - 3325.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Gruber, J. C. Wheat, K. L. Kuhen, D. J. Looney, and F. Wong-Staal
Differential Effects of HIV-1 Protease Inhibitors on Dendritic Cell Immunophenotype and Function
J. Biol. Chem.,
December 14, 2001;
276(51):
47840 - 47843.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Neil, F. Martin, Y. Ikeda, and M. Collins
Postentry Restriction to Human Immunodeficiency Virus-Based Vector Transduction in Human Monocytes
J. Virol.,
June 15, 2001;
75(12):
5448 - 5456.
[Abstract]
[Full Text]
|
 |
|
|
|