DC family welcomes a new arrival

Honey, Karen

doi:10.1038/nri1817

Research Highlight
Published: 01 March 2006

Dendritic cells

DC family welcomes a new arrival

Karen Honey

Nature Reviews Immunology volume 6, page 172 (2006)Cite this article

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Recent studies indicate that there is substantial crosstalk between DCs and NK cells. So, both groups set out to investigate further the relationship between these two cells types. Taieb et al. studied a mouse model of antitumour immunity in which C57BL/6 mice treated with imatinib mesylate (Gleevec; Novartis) generate an antitumour response that is mediated by NK1.1⁺ cells. In this study, combining imatinib mesylate with interleukin-2 (IL-2) increased this antitumour response, and this was associated with a large number of CD11c⁺ cells infiltrating the tumours. Most of the tumour-infiltrating CD11c⁺ cells expressed B220, NK1.1 and other NK-cell markers (such as CD49b and NK group 2, member D (NKG2D)) but not Gr1, which is expressed by plasmacytoid DCs (pDCs). Consistent with these cells being a new subset of DCs, ∼50% of the CD11c⁺B220⁺NK1.1⁺ cells also expressed MHC class II molecules, and cells with this phenotype could be detected in mice lacking lymphocytes and NK cells (that is, mice lacking recombination-activating gene 2 (RAG2) and the common cytokine-receptor γ-chain (γ_c)).

B220⁺NK1.1⁺ DCs isolated from mice treated with imatinib mesylate and IL-2 mediated TRAIL (TNF-related apoptosis-inducing ligand)-dependent tumour-cell lysis. Expression of TRAIL is induced by IFNγ, and when stimulated with either tumour cells or imatinib mesylate and IL-2, these DCs produced large amounts of IFNγ. Importantly, these IKDCs controlled tumour-cell growth when transferred to mice lacking RAG2 and γ_c, indicating that IKDCs induce an effective antitumour response in vivo.

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ORIGINAL RESEARCH PAPERS

Taieb, J. et al. A novel dendritic cell subset involved in tumor immunosurveillance. Nature Med. 12, 214–219 (2006)
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Chan, C. W. et al. Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity. Nature Med. 12, 207–213 (2006)
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