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(Journal of Leukocyte Biology. 2002;72:1037-1045.)
© 2002 by Society for Leukocyte Biology

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

Irina L. Tourkova^*, Zoya R. Yurkovetsky, Andrea Gambotto, Valeria P. Makarenkova^*, Lori Perez^*, Levent Balkir^*, Paul D. Robbins, Michael R. Shurin^*, and Galina V. Shurin^*

Departments of
^* Pathology,
Surgery, and
Immunology, University of Pittsburgh Medical Center and University of Pittsburgh Cancer Institute, and
Department of Molecular Biology and Biochemistry, University of Pittsburgh, Pennsylvania

Correspondence: Galina V. Shurin, Ph.D., Clinical Immunopathology, University of Pittsburgh Medical Center, 5725 CHP MT, 200 Lothrop Street, Pittsburgh, PA 15213. E-mail: shuringv{at}msx.upmc.edu

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 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.

Key Words: apoptosis • immunosuppression • prostate cancer

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