Dendritic cells (DCs) are highly specialised antigen-presenting cells (APCs) that are essential for the initiation and modulation of T cell-mediated immune responses. In order to induce effective CTL responses against most
infections and tumours, DCs must prime both CD4(+) and
CD8(+) antigen-specific T cells. It is, therefore, important in
vaccine design to produce
antigen-delivery systems that lead to the simultaneous presentation of multiple histocompatibility complex (MHC) class I- and class II-restricted antigenic
peptides by DCs. In this study, the
infection of immature mouse bone marrow-derived DCs (BMDCs) with recombinant adenovirus (rAd) vectors led to a marked upregulation of surface costimulatory molecules,
IL-12 p40 production and capacity to stimulate both allogeneic and
antigen-specific T cells. Furthermore,
infection of immature and mature BMDCs with a rAd encoding chicken
ovalbumin (OVA) led to presentation of the
antigen to TCR-transgenic OVA-specific CD4(+) and CD8(+) T cells. In addition, the activation state of responding CD8(+) T cells was further amplified if they recognised
antigen on rAd-transduced BMDCs in the presence of
antigen-specific CD4(+) T cells. The results suggest that rAd-encoded OVA
protein is secreted by BMDCs, taken up by endocytosis and presented in association with
MHC class II molecules for activation of OVA-specific CD4(+) T cells. Consequently, rAd-transduced immature BMDCs become better stimulators of
antigen-specific CD4(+) T cells than rAd-infected mature BMDCs. Taken together, these data have important implications for
vaccine design, and suggest that
infection of immature DCs with rAd encoding MHC class I and class II-restricted
T cell epitopes could be an efficient means of inducing effective immune responses.