|
|
Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-07-2146.

Submitted July 18, 2002
Accepted November 7, 2002
Humoral immune response in mice against a circulating antigen induced by adenoviral transfer is strictly dependent on expression in antigen-presenting cells
Bart R De Geest*, Sophie A Van Linthout, and Desire Collen
Department for Molecular and Cardiovascular Research, Center for Molecular and Vascular Biology, Leuven, Belgium
* Corresponding author; email: Bart.Degeest{at}med.kuleuven.ac.be.
Adenoviral transfer of human apo A-I in Balb/c mice induces a strong humoral immune response against the transgene product when expression is driven from the ubiquitously active CMV promoter but no immune response when driven by the hepatocyte-specific 256 bp apo A-I promoter. Here the hypothesis, that the humoral immune response against the circulating transgene product correlates with its expression in antigen presenting cells, was tested. No humoral immune response was observed after adenoviral transfer of vectors with human apo A-I expression driven by the hepatocyte-specific apo C-II or 1.5 kb human 1-antitrypsin promoter, but antibodies were induced after transfer with vectors driven by the ubiquitously active U1b promoter and the murine MHCII E promoter. A strict correlation was observed between antigen expression in the spleen and the occurrence of an immune response. Co-injection of the 1.5 kb human 1-antitrypsin and the murine MHCII E promoter driven vectors resulted in a very short-lived humoral immune response against human apo A-I, suggesting that the time-course of human apo A-I expression is a critical determinant of the development of tolerance for human apo A-I. High titers of antibodies against human apo A-I after subcutaneous gene transfer with the MHCII E promoter driven vector underscore the potential of this promoter for vaccination purposes. In conclusion, humoral immune response in mice against a circulating antigen induced by adenoviral transfer is strictly dependent on expression in antigen-presenting cells.

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

|
 |

|
 |
 
B. D. Brown, A. Cantore, A. Annoni, L. S. Sergi, A. Lombardo, P. Della Valle, A. D'Angelo, and L. Naldini
A microRNA-regulated lentiviral vector mediates stable correction of hemophilia B mice
Blood,
December 15, 2007;
110(13):
4144 - 4152.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Annoni, M. Battaglia, A. Follenzi, A. Lombardo, L. Sergi-Sergi, L. Naldini, and M.-G. Roncarolo
The immune response to lentiviral-delivered transgene is modulated in vivo by transgene-expressing antigen-presenting cells but not by CD4+CD25+ regulatory T cells
Blood,
September 15, 2007;
110(6):
1788 - 1796.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. Cao, E. Dobrzynski, L. Wang, S. Nayak, B. Mingle, C. Terhorst, and R. W. Herzog
Induction and role of regulatory CD4+CD25+ T cells in tolerance to the transgene product following hepatic in vivo gene transfer
Blood,
August 15, 2007;
110(4):
1132 - 1140.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Dobrzynski, J. C. Fitzgerald, O. Cao, F. Mingozzi, L. Wang, and R. W. Herzog
Prevention of cytotoxic T lymphocyte responses to factor IX-expressing hepatocytes by gene transfer-induced regulatory T cells
PNAS,
March 21, 2006;
103(12):
4592 - 4597.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Dobrzynski and R. W. Herzog
Tolerance Induction by Viral In Vivo Gene Transfer
Clin. Med. Res.,
November 1, 2005;
3(4):
234 - 240.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Dobrzynski, F. Mingozzi, Y.-L. Liu, E. Bendo, O. Cao, L. Wang, and R. W. Herzog
Induction of antigen-specific CD4+ T-cell anergy and deletion by in vivo viral gene transfer
Blood,
August 15, 2004;
104(4):
969 - 977.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Follenzi, M. Battaglia, A. Lombardo, A. Annoni, M. G. Roncarolo, and L. Naldini
Targeting lentiviral vector expression to hepatocytes limits transgene-specific immune response and establishes long-term expression of human antihemophilic factor IX in mice
Blood,
May 15, 2004;
103(10):
3700 - 3709.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Zhang, L. Xu, M. E. Haskins, and K. Parker Ponder
Neonatal gene transfer with a retroviral vector results in tolerance to human factor IX in mice and dogs
Blood,
January 1, 2004;
103(1):
143 - 151.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|