Ready for Prime Time: NK Cell Priming by Dendritic Cells

Laboratory of Immunogenetics, NIAID-NIH, 12441 Parklawn Drive, Rockville, MD 20852, USA.
Immunity (Impact Factor: 21.56). 05/2007; 26(4):385-7. DOI: 10.1016/j.immuni.2007.04.001
Source: PubMed


Natural killer (NK) cells were long thought to respond directly to infected cells and tumor cells. In this issue of Immunity, Lucas et al. (2007) repeal this view by showing that NK cells acquire functionality through priming by dendritic cells.

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Available from: Eric O. Long
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    • "However, resting NK cells from laboratory mice react only weakly to stimuli unless mice or cells are prestimulated by toll-like receptor (TLR) agonists, cytokines or infection (Long 2007). In mice, NK cells have been reported to be almost absent from lymph nodes (LNs), to not contain perforin or granzyme B (Gzmb), and quickly die in cytokine-free culture (Fehniger et al. 2007; Long 2007). In contrast, human NK cells are abundant in LNs, contain perforin and Gzmb in the resting state, can be triggered by activating receptors and show better survival (Fehniger et al. 2003; Ferlazzo et al. 2004; Bryceson et al. 2006); moreover, cultured human NK cells respond more strongly than murine counterparts (Bergman et al. 2000). "
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    ABSTRACT: Recent reports have shown that natural killer (NK) cells may be long-lived, possess memory-like features and may need microbial priming to become fully reactive. Thus, the notion that these cells are typically innate, nonadaptive lymphocytes has been challenged. If microbial priming is essential for functional maturity, it is necessary to raise the question whether NK cells of laboratory mice, kept under strict hygienic conditions, represent these cells adequately. In their natural habitat, mice will encounter microbes to a greater extent, and we here investigated whether NK cells of feral mice showed signs of being primed. In comparison with C57BL/6 mice raised under specific pathogen-free conditions, NK cells from feral mice had high expression of CD69, KLRG1, granzyme B and NKp46 and a higher proportion of CD27+ cells, mostly CD11b-, as well as a higher presence in peripheral lymph nodes. Following cytokine stimulation, feral mouse NK cells had quickly inducible CD25 expression and a stronger interferon-gamma response. These findings indicate a high degree of pre-activation of NK cells of free-living mice, indicating a strong environmental impact on NK cells, which may be highly relevant for interpretation of studies in the mouse model.
    Full-text · Article · Sep 2011 · Molecular Ecology
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    • "DCs function in the initiation of the anti-tumor immune responses through the recruitment and the activation of T-cells [34], B-cells [5] and NK cells [35] into tumors. So, we examined these populations of immune cells in tumors inoculated with the RBP-J deficient and the control DCs in mice. "
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    ABSTRACT: Dendritic cells (DCs) are professional antigen presenting cells that initiate specific immune responses against tumor cells. Transcription factor RBP-J-mediated Notch signaling regulates DC genesis, but whether this pathway regulates DC function in anti-tumor immunity remains unclear. In the present work we attempted to identify the role of Notch signaling in DC-mediated anti-tumor immune response. When DCs were co-inoculated together with tumor cells, while the control DCs repressed tumor growth, the RBP-J deficient DCs had lost tumor repression activity. This was most likely due to that DCs with the conditionally ablated RBP-J were unable to evoke anti-tumor immune responses in the solid tumors. Indeed, tumors containing the RBP-J deficient DCs had fewer infiltrating T-cells, B-cells and NK-cells. Similarly, the draining lymph nodes of the tumors with RBP-J-/- DCs were smaller in size, and contained fewer cells of the T, B and NK lineages, as compared with the controls. At the molecular level, the RBP-J deficient DCs expressed lower MHC II, CD80, CD86, and CCR7, resulting in inefficient DC migration and T-cell activation in vitro and in vivo. T-cells stimulated by the RBP-J deficient DCs did not possess efficient cytotoxicity against tumor cells, in contrast to the control DCs. The RBP-J-mediated Notch signaling is essential for DC-dependent anti-tumor immune responses. The deficiency of RBP-J impairs the DC-based anti-tumor immunity through affecting series of processes including maturation, migration, antigen presentation and T-cell activation. The Notch signaling pathway might be a target for the establishment of the DC-based anti-tumor immunotherapies.
    Full-text · Article · Apr 2010 · Molecular Cancer
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    • "However, DCs are also inducers of tolerance by mediating deletion of selfreactive thymocytes and anergy of mature T cells or generating regulatory T cells, which display inhibitory functions on T and NK cells. DC can also modulate the innate players of immunity that is the NK and NKT cell compartments (Ikarashi et al., 2001; Zitvogel, 2002; Long, 2007; Lucas et al., 2007). "
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    ABSTRACT: On the basis of experimental models and some human data, we can assume that tumor outgrowth results from the balance between immunosurveillance (the extrinsic tumor suppressor mechanisms) and immunosubversion dictated by transformed cells and/or the corrupted surrounding microenvironment. Cancer immunosurveillance relies mainly upon conventional lymphocytes exerting either lytic or secretory functions, whereas immunosubversion results from the activity of regulatory T or suppressor myeloid cells and soluble mediators. Although specific tools to target or ablate dendritic cells (DCs) became only recently available, accumulating evidence points to the critical role of the specialized DC system in dictating most of the conventional and regulatory functions of tumor-specific T lymphocytes. Although DC can be harnessed to silence tumor development, tumors in turn can exploit DC to evade immunity. Indeed, DCs harbor defects in their differentiation and stimulatory functions in cancer-bearing hosts and can actively promote T-cell tolerance to self-tumor antigens. In this review, we will focus on the dual role of DC during tumor progression and discuss pharmacoimmunological strategies to harness DC against cancer.
    Full-text · Article · Nov 2008 · Oncogene
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