Previous Article | Next Article ![]()
Journal of Virology, December 1999, p. 10245-10253, Vol. 73, No. 12
Department of Immunohematology and Blood
Bank1 and Laboratory of Molecular
Carcinogenesis,
Received 1 June 1999/Accepted 3 September 1999
Human monocyte-derived dendritic cells (DC) infected with
recombinant adenoviruses (rAd) are promising candidate vaccines for
inducing protective immunity against pathogens and tumors. However,
since some viruses are known to negatively affect DC function, it is
important to investigate the interactions between rAd and DC. We now
show that infection by rAd enhances the immunostimulatory capacity of
immature human monocyte-derived DC through the upregulation of the
costimulatory molecules CD80, CD86, and CD40 and the major histocompatibility complex class I and II molecules. Although rAd
infection fails to induce the secretion of interleukin-12 (IL-12) and
only marginally induces the expression of the DC maturation marker
CD83, it acts in synergy with CD40 triggering in rendering DC fully
mature. rAd-infected DC triggered through CD40 produce more IL-12 and
are more efficient in eliciting T-helper type 1 responses than DC
activated by CD40 triggering only. rAd lacking one or more of the early
regions, E1, E2A, E3, and E4, which play an important role in
virus-host cell interactions are equally capable of DC activation.
Efficient DC infection requires a high multiplicity of infection
(>1,000), a fact which can be attributed to the absence of the
coxsackievirus and adenovirus receptor on this cell type. Despite the
poor ability of DC to be infected by rAd, which may be improved by
targeting rAd to alternative DC surface molecules, DC infected with all
currently tested rAd constitute potent immunostimulators. Our study
provides new insights into the interactions between two highly
promising vaccine components, rAd and DC, and indicates that their
combination into one vaccine may be very advantageous for the
stimulation of T-cell immunity.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Adenoviruses Activate Human Dendritic Cells without Polarization
toward a T-Helper Type 1-Inducing Subset
*
Corresponding author. Mailing address: Department of
Immunohematology and Blood Bank, Building E3-Q, Leiden University
Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands. Phone: 31 71 526 4007. Fax: 31 71 521 6751. E-mail:
D.G.Rea{at}Immunohematology.Medfac.Leidenuniv.nl.
Journal of Virology, December 1999, p. 10245-10253, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
| J. Bacteriol. | Mol. Cell. Biol. | Microbiol. Mol. Biol. Rev. |
|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|