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Overexpression of interleukin‐12 enables dendritic cells to activate NK cells and confer systemic antitumor immunity
Author(s) -
Miller George,
Lahrs Svenja,
DeMatteo Ronald P.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0900fje
Subject(s) - interleukin 12 , interleukin 21 , janus kinase 3 , microbiology and biotechnology , lymphokine activated killer cell , interleukin 15 , in vivo , biology , dendritic cell , secretion , immunology , chemistry , cytokine , cancer research , interleukin , in vitro , cytotoxic t cell , immune system , t cell , endocrinology , biochemistry
Dendritic cells (DC) are initiators of T cell‐mediated immunity. However, less is known about the relationship between DC and natural killer (NK) cells, and direct evidence of their interaction in vivo is scarce. Interleukin (IL)‐12 is an activator of both DC and NK cells. We postulated that secretion of IL‐12 by DC would enable them to activate NK cells. Bone marrow‐derived DC propagated only in granulocyte macrophage colony‐stimulating factor did not activate NK cells. In contrast, DC engineered to express IL‐12 markedly stimulated NK cells as determined by coculture experiments in vitro , assays of NK cells isolated from treated animals, and survival experiments in a systemic tumor model. Activation depended on both DC‐NK cellular interaction and secretion of IL‐12. Adoptive transfer of DC expressing IL‐12 to mice markedly increased NK cell interferon‐γ production and lytic activity in vivo . Treated mice were also protected against B16 melanoma hepatic metastases. The in vivo effects on NK cells were DC‐specific. Administration of IL‐12 protein alone or melanoma cells or fibroblasts engineered to secrete IL‐12 were only weakly activating. Our findings demonstrate that IL‐12 expression by DC enables them to activate NK cells and provide evidence for a substantial DC‐NK relationship in vivo .