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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.

Adenoviruses Activate Human Dendritic Cells without Polarization toward a T-Helper Type 1-Inducing Subset

Delphine Rea,1,* Frederik H. E. Schagen,2 Rob C. Hoeben,2 Majid Mehtali,3 Menzo J. E. Havenga,4 Rene E. M. Toes,1 Cornelis J. M. Melief,1 and Rienk Offringa1

Department of Immunohematology and Blood Bank1 and Laboratory of Molecular Carcinogenesis, Department of Molecular Cell Biology,2 Leiden University Medical Center, 2300 RC Leiden, and IntroGene B.V., 2301 CA Leiden,4 The Netherlands, and Transgene S.A., 67000 Strasbourg, France3

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.

* 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.


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