TY - JOUR
T1 - Increased function and survival of IL-15-transduced human dendritic cells are mediated by up-regulation of IL-15rα and Bcl-2
AU - Tourkova, Irina L.
AU - Yurkovetsky, Zoya R.
AU - Gambotto, Andrea
AU - Makarenkova, Valeria P.
AU - Perez, Lori
AU - Balkir, Levent
AU - Robbins, Paul D.
AU - Shurin, Michael R.
AU - Shurin, Galina V.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Immunosuppression
KW - Prostate cancer
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UR - http://www.scopus.com/inward/citedby.url?scp=0036855828&partnerID=8YFLogxK
M3 - Article
C2 - 12429727
AN - SCOPUS:0036855828
SN - 0741-5400
VL - 72
SP - 1037
EP - 1045
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 5
ER -