Increased function and survival of IL-15-transduced human dendritic cells are mediated by up-regulation of IL-15Ralpha and Bcl-2

It has been recently demonstrated that dendritic cells (DC) coincubated with interleukin (IL)-15 express high levels of the Bcl-2 family of proteins and display an increased resistance to tumor-induced apoptotic death. Here, the phenotype, functions, and survival of human DC transduced with adenoviral vector encoding the human IL-15 gene were studied. The transduction of DC with the IL-15 gene resulted in a significant elevation of expression of CD83, CD86, and CD40 molecules, which was blocked by anti-IL-15 monoclonal antibodies. This effect was also accompanied by an increased production of IL-12 and stimulated ability of DC to induce T cell proliferation. Furthermore, transduction of DC with the IL-15 gene significantly increased their resistance to prostate cancer-induced apoptosis: Overexpression of IL-15 on DC blocked tumor-induced inhibition of Bcl-2 expression and prolonged DC survival after coincubation with tumor cells. Finally, overexpression of IL-15 in DC was associated with a higher level of expression of IL-15 receptor alpha chain mRNA. In summary, these results suggest that transduction of DC with the IL-15 gene markedly stimulates DC function and protects them from tumor-induced apoptosis.