Overexpression of interleukin-12 enables dendritic cells to activate NK cells and confer systemic antitumor immunity Journal Article
| Authors: | Miller, G.; Lahrs, S.; DeMatteo, R. P. |
| Article Title: | Overexpression of interleukin-12 enables dendritic cells to activate NK cells and confer systemic antitumor immunity |
| Abstract: | 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-gamma 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. |
| Keywords: | genetics; flow cytometry; methodology; mouse; animal; cytology; metabolism; animals; mice; interleukin 2; dendritic cell; pathology; tumor cells, cultured; biosynthesis; immunology; dendritic cells; cell culture; neoplasms, experimental; natural killer cell; killer cells, natural; immunophenotyping; experimental neoplasm; antigens, cd; neoplasm transplantation; leukocyte antigen; adoptive immunotherapy; immunotherapy, adoptive; interleukin-2; cancer transplantation; coculture; coculture techniques; article |
| Journal Title: | FASEB Journal |
| Volume: | 17 |
| Issue: | 6 |
| ISSN: | 0892-6638 |
| Publisher: | Federation of American Societies for Experimental Biology |
| Date Published: | 2003-04-01 |
| Start Page: | 728 |
| End Page: | 730 |
| Language: | English |
| PUBMED: | 12594171 |
| PROVIDER: | scopus |
| DOI: | 10.1096/fj.02-0900fje |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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