Adenoviruses activate human dendritic cells without polarization toward a T-helper type 1-inducing subset

Human monocyte-derived dendritic cells (DC) infected with recombinant adeno viruses (rAd) are promising candidate vaccines for inducing protective immu nity against pathogens and tumors. However, since some viruses are known to negatively affect DC function, it is important to investigate the interact ions between rAd and DC, We now show that infection by rAd enhances the imm unostimulatory capacity of immature human monocyte-derived DC through the u pregulation of the costimulatory molecules CD80, CD86, and CD40 and the maj or histocompatibility complex class I and II molecules. Although rAd infect ion fails to induce the secretion of interleukin-12 (IL-12) and only margin ally induces the expression of the DC maturation marker CD83, it acts in sy nergy with CD40 triggering in rendering DC fully mature, rAd-infected DC tr iggered 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 l acking 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 a ctivation, Efficient DC infection requires a high multiplicity of infection (>1,000), a fact which can be attributed to the absence of the coxsackievi rus 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 alterna tive DC surface molecules, DC infected with all currently tested rAd consti tute potent immunostimulators, Our study provides new insights into the int eractions 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.