Human Dendritic Cells Activate Resting Natural Killer (NK) Cells and Are Recognized via the NKp30 Receptor by Activated NK Cells

By G. Ferlazzo, M. L. Tsang, L. Moretta, G. Melioli, R. Steinman, C. Münz. Journal of Experimental Medicine, 2002

1,108 citations recorded by the source corpus.

During the innate response to many inflammatory and infectious stimuli, dendritic cells (DCs) undergo a differentiation process termed maturation. Mature DCs activate antigen-specific naive T cells. Here we show that both immature and mature DCs activate resting human natural killer (NK) cells. Within 1 wk the NK cells increase two– to fourfold in numbers, start secreting interferon (IFN)-γ, and acquire cytolytic activity against the classical NK target LCL721.221. The DC-activated NK cells then kill immature DCs efficiently, even though the latter express substantial levels of major histocompatibility complex (MHC) class I. Similar results are seen with interleukin (IL)-2–activated NK cell lines and clones, i.e., these NK cells kill and secrete IFN-γ in response to immature DCs. Mature DCs are protected from activated NK lysis, but lysis takes place if the NK inhibitory signal is blocked by a human histocompatibility leukocyte antigen (HLA)-A,B,C–specific antibody. The NK activating signal mainly involves the NKp30 natural cytotoxicity receptor, and not the NKp46 or NKp44 receptor. However, both immature and mature DCs seem to use a NKp30 independent mechanism to act as potent stimulators for resting NK cells. We suggest that DCs are able to control directly the expansion of NK cells and that the lysis of immature DCs can regulate the afferent limb of innate and adaptive immunity.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/a1f812f952f2f5732bbb88feae0f0fd109546462

How researchers see this paper

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In Immunology

1. M. Smyth
2. Robert Schreiber
3. G. Dunn
4. Eric G. Pamer
5. Lloyd J. Old
6. F. Sallusto
7. A. Lanzavecchia
8. L. Moretta

Citations in the corpus

• 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”
• 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”
• TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. (2003, background): “This monocyte subset ex- cells were shown to induce IFN- secretion by NK cells presses CCR2 and thus may represent a precursor of (Ferlazzo et al., 2002; Gerosa et al., 2002).”
• Unravelling natural killer cell function: triggering and inhibitory human NK receptors (2004, background): “NCRs play a major role in the NK-mediated killing of most tumor cell lines, as revealed by monoclonal antibody (mAb)-mediated receptor-masking experiments (Moretta et al, 2001).”
• 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”
• Controlling NK Cell Responses: Integration of Signals for Activation and Inhibition (2013, background): “NKp30 is involved in the activation of NK cells by dendritic cells (DCs) (25).”