Contact-dependent Stimulation and Inhibition of Dendritic Cells by Natural Killer Cells

By D. Piccioli, S. Sbrana, E. Melandri, N. Valiante. Journal of Experimental Medicine, 2002

778 citations recorded by the source corpus.

Natural killer (NK) cells and dendritic cells (DCs) are two distinct cell types of innate immunity. It is known that the in vitro interaction of human NK cells with autologous DCs results in DC lysis. Here we show that contact-dependent interactions between activated human NK cells and immature DCs (iDCs) provides a “control switch” for the immune system. At low NK/DC ratios, this interaction dramatically amplifies DC responses, whereas at high ratios it completely turns off their responses. Specifically, culture of activated human NK cells with iDCs, at low NK/DC ratios (1:5), led to exponential increases in DC cytokine production, which were completely dependent on cell-to-cell contact. DC maturation was also driven by cognate interactions with NK cells and maturation was dependent on endogenously produced TNF-α in the culture. At slightly higher NK/DC ratios (5:1), inhibition of DC functions was the dominant feature due to potent killing by the autologous NK cells. Resting NK cells also stimulated autologous DC maturation in a TNF-α/contact-dependent manner, however, increasing the NK/DC ratio only led to an enhancement of this effect.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/8c69fc05dcb5aab276cfc03510745f3fdb7a87bd

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In Immunology

1. M. Smyth
2. Robert Schreiber
3. G. Dunn
4. Lloyd J. Old
5. F. Sallusto
6. A. Lanzavecchia
7. J. Trapani
8. H. Yagita

Citations in the corpus

• Induced recruitment of NK cells to lymph nodes provides IFN-γ for TH1 priming (2004, background): “Depending on the context, in vitro human NK cells can either kill immature DCs or induce their maturation and the production of IL-12, thereby promoting T H 1 polarizatio”
• The Abundant NK Cells in Human Secondary Lymphoid Tissues Require Activation to Express Killer Cell Ig-Like Receptors and Become Cytolytic1 (2004, background): “We and others have previously demonstrated that immature dendritic cells can be lysed by NK cells (24, 28).”
• Cutting Edge: Murine Dendritic Cells Require IL-15Rα to Prime NK Cells1 (2004, background): “tivation appears to be cell-contact dependent (5, 23).”
• New aspects of natural-killer-cell surveillance and therapy of cancer (2002, background): “Priming of adaptive tumour immunity by NK cells It has recently become apparent that NK cells might also influence development of the adaptive immune response by interacting with DC”
• Cancer immunoediting: from immunosurveillance to tumor escape (2002, background): “In the draining lymph node, the newly immigrated dendritic cells induce tumor-specific CD4 + T helper cells expressing IFN-γ (T H 1 cells) that in turn facilitate the development of tumor-specific CD8 + T cell”
• Functional significance of the perforin/granzyme cell death pathway (2002, background): “cgi?l=912">CD1d -restricted NKT cells, regulate responses to peptide antigens that are presented on MHC class I molecules and to glycolipids, respectivel”
• Functions of natural killer cells (2008, background): “First, NK cells can kill immature DC in humans and mice, thereby influencing DC homeostasis, but also potentially limiting DC-based vaccination efficac”