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BioMed Research International
Volume 2013 (2013), Article ID 460706, 18 pages
Research Article

Natural Killer Dendritic Cells Enhance Immune Responses Elicited by α-Galactosylceramide-Stimulated Natural Killer T Cells

1Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul 143-747, Republic of Korea
2Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea

Received 31 December 2012; Revised 28 April 2013; Accepted 13 May 2013

Academic Editor: Anton M. Jetten

Copyright © 2013 Sung Won Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited by α-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γ by NKDCs after α-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated following α-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited by α-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated by α-GC-stimulated NKT cells in vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.