Dendritic cells and HIV-1 infection. Dendritic cells (DC) are potent antigen presenting cells responsible for the activation of naive T cells and therefore are potential targets for HIV-1. In vitro studies have demonstrated that DC are rapidly and efficiently infected with HIV-1. Productive infection is mediated in part by chemokine receptors that function as coreceptors. The infection leads to loss of DC maturation, alteration of DC morphology, downregulation of MHC class I and class II molecules, and the production of interferon gamma (IFN-gamma). Viral proteins produced as a result of HIV-1 replication affect DC function, leading to apoptosis and altered cytokine secretion. These alterations can be reversed by IL-12, which can be supplied by a novel DC-based vaccine (DC/SFU), where the vaccine is made up of autologous, interleukin-2 (IL-2) expanded T cells and a recombinant vaccinia expressing IL-12. This vaccine is also able to inhibit viral replication and downmodulate viral transcription. This vaccine reverses the effects of HIV-1 infection on DC and stimulates autologous T cells to proliferate and produce IFN-gamma, thereby producing a DC-induced immune response. Further studies are underway to determine whether this vaccination regimen can prevent HIV-1 infection in humans.