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Published online before print March 1, 2007

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(Journal of Leukocyte Biology. 2007;81:1422-1433.)
© 2007 by Society for Leukocyte Biology

Natural killer dendritic cells are an intermediate of developing dendritic cells

Li Chen^*, Edward Calomeni^*, Jing Wen^*, Keiko Ozato, Rulong Shen^* and Jian-Xin Gao^*,,1

^* Department of Pathology and
Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, Ohio, USA; and
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

¹ Correspondence: Department of Pathology, The Ohio State University Medical Center, 129 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA. E-mail: jian-xin.gao{at}osumc.edu

NK dendritic cells (DCs; NKDCs) appear to emerge as a distinct DC subset in humans and rodents, which have the functions of NK cells and DCs. However, the developmental relationship of NKDCs (CD11c⁺NK1.1⁺) to CD11c⁺NK1.1^– DCs has not been addressed. Herein, we show that NKDCs exist exclusively in the compartment of CD11c⁺MHC II^– cells in the steady state and express variable levels of DC subset markers, such as the IFN-producing killer DC marker B220, in a tissue-dependent manner. They can differentiate into NK1.1^– DCs, which is accompanied by the up-regulation of MHC Class II molecules and down-regulation of NK1.1 upon adoptive transfer. However, NK cells (NK⁺CD11c^–) did not differentiate into NK1.1⁺CD11c⁺ cells upon adoptive transfer. Bone marrow-derived Ly6C⁺ monocytes can be a potential progenitor of NKDCs, as some of them can differentiate into CD11c⁺NK1.1⁺ as well as CD11c⁺NK1.1^– cells in vivo. The steady-state NKDCs have a great capacity to lyse tumor cells but little capability to present antigens. Our studies suggest that NKDCs are an intermediate of developing DCs. These cells appear to bear the unique surface phenotype of CD11c⁺NK1.1⁺MHC II^– and possess strong cytotoxic function yet show a poor ability to present antigen in the steady state. These findings suggest that NKDCs may play a critical role in linking innate and adaptive immunity.

Key Words: differentiation • IFN-producing killer dendritic cells (IKDC) • Ly6C⁺ monocytes

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