Pallandre, J. R. et al. Dendritic cell and natural killer cell cross-talk: a pivotal role of CX3CL1 in NK cytoskeleton organization and activation. Blood 112, 4420-4424

Inserm U645, EFS Bourgogne Franche Comté, University of Franche-Comté, IFR133, Besançon, France.
Blood (Impact Factor: 10.45). 09/2008; 112(12):4420-4. DOI: 10.1182/blood-2007-12-126888
Source: PubMed


Initial molecular events leading to natural killer lymphocyte (NK) and dendritic cell (DC) interactions are largely unknown. Here, the role of CX3CL1 (fractalkine), a chemokine expressed on mature dendritic cells (mDCs) has been investigated. We show that CX3CL1 promotes NK activation by mDCs. After blocking of CX3CL1 by antibody, no activation occurred but major histocompatibility complex (MHC) class I neutralization restored DC-mediated NK activation, suggesting an interaction between CX3CL1 signaling and the functioning of inhibitory KIR. Then the YTS NK cell line, in which the inhibitory receptor KIR2DL1 had been introduced, was used. The presence of KIR2DL1 did not decrease YTS activation by HLA-Cw4 DC when CX3CL1 was functional. In contrast, CX3CL1 neutralization led to killer cell immunoglobulin-like receptor (KIR) phosphorylation and SHP-1 recruitment in YTS(KIR2DL1) cultured with HLA-Cw4 mDCs. Moreover, CX3CL1 neutralization promoted dispersion of lipid rafts and the formation of a multiprotein complex required for cytoskeletal rearrangements in YTS NK cells. These findings point to a pivotal role of CX3CL1 in the activation of resting NK cells by mature DCs.

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    • "In general, the formation of stimulatory synapses between DCs and NK cells plays a critical role during NK cell activation induced by DC-derived cytokines, including IL-12 (47). Also, the interaction of CXC3CL1 expressed on DCs with CX3CR1 on NK cells results in IFN-γ release by NK cells (48) and it has been shown that influenza virus-infected DCs can support IFN-γ production by triggering the activating receptors NKp46 and NKG2D (49). "
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    ABSTRACT: In recent years, the essential role of bi-directional cross-talk between natural killer (NK) and dendritic cells (DC) during immune responses has been clearly elucidated. In particular, this cross-talk results in the development of an efficient innate response, through DC-mediated NK cell activation, and a potent adaptive immune response, through NK-mediate DC editing and maturation. Recently, some novel human DC subsets have been identified: migratory DCs in afferent lymph and draining lymph nodes; CLEC9A(+)/BDCA3(+) (CD141) DCs in interstitial dermis, liver, lung; inflammatory DCs in several inflammatory fluids. At the same time, it has been shown that also human NK cells are present in these compartments. Here, we will review the most recent findings on NK/DC cross-talk and we will discuss the necessity of acquiring more complete knowledge about these interactions in view of the new information available on both DC and NK cell subsets.
    Frontiers in Immunology 04/2014; 5:159. DOI:10.3389/fimmu.2014.00159
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    • "DCs and NK cells specialize in complementary functions, including IL-12 or IFN-α/β secretion and antigen presentation for the former, and IFN-γ secretion and killing of infected or tumor cells for the latter . Thus, the outcome of NK-DC crosstalk is likely to increase lytic activity against malignancies compared to NK cell cytotoxicity alone (Walzer et al., 2005; Pallandre et al., 2008; Wehner et al., 2009; Jacobs and Ullrich, 2012). Additional investigations are "
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    ABSTRACT: Allogeneic natural killer (NK) cells are used for adoptive immunotherapy after stem cell transplantation. In order to overcome technical limitations in NK cell purification and activation, the following study investigates the impact of different variables on NK cell recovery, cytotoxicity, and T-cell depletion during good manufacturing practice (GMP)-grade NK cell selection. Forty NK cell products were derived from 54 unstimulated donor leukaphereses using immunomagnetic CD3 T-cell depletion, followed by a CD56 cell enrichment step. For T-cell depletion, either the depletion 2.1 program in single or double procedure (D2.11depl, n = 18; D2.12depl, n = 13) or the faster depletion 3.1 (D3.1, n = 9) was used on the CliniMACS instrument. Seventeen purified NK cell products were activated in vitro by IL-2 for 12 days. The whole process resulted in a median number of 7.59 × 10(8) CD56(+)CD3(-) cells with both purity and viability of 94%, respectively. The T-cell depletion was significantly better using D2.11depl/2depl compared to D3.1 (log 4.6/log 4.9 vs. log 3.7; p < 0.01) and double procedure in two stages led always to residual T cells below 0.1%. In contrast D3.1 was superior to D2.11depl/2depl with regard to recovery of CD56(+)CD3(-) NK cells (68% vs. 41%/38%). Concomitant monocytes and especially IL-2 activation led to increased NK cell activity against malignant target cells compared to unstimulated NK cells, which correlated with both up-regulation of natural cytotoxicity receptors and intracellular signaling. Overall, wide variations in the NK cell expansion rate and the distribution of NK cell subpopulations were found. In conclusion, our results indicate that GMP-grade purification of NK cells might be improved by a sequential processing of T-cell depletion program D2.1 and D3.1. In addition NK cell expansion protocols need to be further optimized.
    Frontiers in Oncology 05/2013; 3:118. DOI:10.3389/fonc.2013.00118
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