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Increased function and survival of IL‐15‐transduced human dendritic cells are mediated by up‐regulation of IL‐15Rα and Bcl‐2
Author(s) -
Tourkova Irina L.,
Yurkovetsky Zoya R.,
Gambotto Andrea,
Makarenkova Valeria P.,
Perez Lori,
Balkir Levent,
Robbins Paul D.,
Shurin Michael R.,
Shurin Galina V.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.5.1037
Subject(s) - biology , cd86 , apoptosis , signal transduction , cd40 , cancer research , transduction (biophysics) , dendritic cell , microbiology and biotechnology , transfection , cell culture , t cell , immunology , cytotoxic t cell , antigen , immune system , in vitro , biochemistry , genetics
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.