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

• Published in: Journal of leukocyte biology Vol. 72; no. 5; pp. 1037 - 1045
• Main Authors: Tourkova, Irina L., Yurkovetsky, Zoya R., Gambotto, Andrea, Makarenkova, Valeria P., Perez, Lori, Balkir, Levent, Robbins, Paul D., Shurin, Michael R., Shurin, Galina V.
• Format: Journal Article
• Language: English
• Published: Society for Leukocyte Biology 01-11-2002
• Subjects: apoptosis; immunosuppression; prostate cancer
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.72.5.1037

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 α 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.