Natural killer cells: Walking three paths down memory lane

Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Trends in Immunology (Impact Factor: 10.4). 03/2013; 34(6). DOI: 10.1016/
Source: PubMed


Immunological memory has traditionally been regarded as a unique feature of the adaptive immune response, mediated in an antigen-specific manner by T and B lymphocytes. All other hematopoietic cells, including natural killer (NK) cells, are classified as innate immune cells, which have been considered short-lived but can respond rapidly against pathogens in a manner not thought to be driven by antigen. Interestingly, NK cells have recently been shown to survive long term after antigen exposure and subsequently mediate antigen-specific recall responses. In this review, we address the similarities between, and the controversies surrounding, three major viewpoints of NK memory that have arisen from these recent studies: (i) mouse cytomegalovirus (MCMV)-induced memory; (ii) cytokine-induced memory; and (iii) liver-restricted memory cells.

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Available from: Yosuke Kamimura, Jun 05, 2014
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    • "In regards to the latter, NK cells have been described as having some aspects of memory, with changed phenotype lasting long after exposure to infection [35] [36]. In addition to detectible receptor expression, NK cells were shown here to respond to the TLR1/2 agonist, Pam3sk4, and this induced activity correlated with hBD-3 induced activity (Fig. 6B). "
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    ABSTRACT: We previously showed that human beta defensin-3 (hBD-3) activates mDC via TLR1/2. Here we investigated the effects of hBD-3 on NK cell activation state and effector functions. We observed that hBD-3 activates PBMC to secrete IFN-γ and kill K562 and HUH hepatoma target cells in an NK dependent fashion, and both TLR1/2 and CCR2 are involved. TLR1, TLR2 and CCR2 were expressed on NK cells, and in purified NK culture experiments we observed hBD-3 to directly act on NK cells, resulting in CD69 upregulation and IFNγ secretion. We also observed mDC-hBD-3 enhanced NK cytolytic activity and IFNγ production. These results implicate hBD-3 in its ability to directly activate NK cells and increase NK cell effector function, as well as promote mDC-dependent NK activity. HBD-3 may therefore act as a mediator of innate cell interactions that result in bridging of innate and adaptive immunity. Published by Elsevier Inc.
    Cellular Immunology 06/2015; 297(2). DOI:10.1016/j.cellimm.2015.06.004 · 1.92 Impact Factor
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    • "Prior studies have established that NK cells can mount an immune response with many of the features of adaptive immunity when challenged with viruses or chemical haptens (O'Leary et al., 2006; Sun et al., 2009a, 2010; Paust et al., 2010; Min-Oo et al., 2013). Here, we have examined whether alloantigens also elicit the expansion of alloantigen-specific NK cells with enhanced responses upon rechallenge. "
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    ABSTRACT: Natural killer (NK) cells provide important host defense against microbial pathogens and can generate a population of long-lived memory NK cells after infection or immunization. Here, we addressed whether NK cells can expand and differentiate after alloantigen stimulation, which may be important in hematopoietic stem cell and solid tissue transplantation. A subset of NK cell in C57BL/6 mice expresses the activating Ly49D receptor that is specific for H-2D(d). These Ly49D(+) NK cells can preferentially expand and differentiate when challenged with allogeneic H-2D(d) cells in the context of an inflammatory environment. H-2D(d) is also recognized by the inhibitory Ly49A receptor, which, when coexpressed on Ly49D(+) NK cells, suppresses the expansion of Ly49D(+) NK cells. Specificity of the secondary response of alloantigen-primed NK cells was defined by the expression of activating Ly49 receptors and regulated by the inhibitory receptors for MHC class I. Thus, the summation of signals through a repertoire of Ly49 receptors controls the adaptive immune features of NK cells responding to allogeneic cells.
    Journal of Experimental Medicine 11/2014; 211(12). DOI:10.1084/jem.20140798 · 12.52 Impact Factor
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    • "This view has been steadily upgraded in recent years. It has been shown for example in mice that infection with viruses and other pathogens determines the expansion of specific NK cell subsets (29–31) which maintain for prolonged periods of time the ability to produce increased amounts of TNFα and IFNγ. This observation is reminiscent of memory T cell function thus suggesting a possible memory-like feature of NK cells. "
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    ABSTRACT: Natural killer (NK) cell function is regulated by a balance between the triggering of activating and inhibitory receptors expressed on their surface. A relevant effort has been focused so far on the study of KIR carriage/expression setting the basis for NK cell education and self-tolerance. Focus on the evolution and regulation of activating NK receptors has lagged behind so far. Our understanding of activating receptor expression and regulation has recently improved by evidences derived from in vitro and in vivo studies. Virus infection - either acute or chronic - determines preferential expansion of NK cells with specific phenotype, activating receptors, and with recall-like functional activity. Studies on patients with viral infection (HIV and HCV) and specific diverging clinical courses confirm that inter-individual differences may exist in baseline expression of natural cytotoxicity receptors (NKp46 and NKp30). The findings that patients with divergent clinical courses have different kinetics of activating receptor density expression upon NK cell activation in vitro provide an additional, time-dependent, functional parameter. Kinetic changes in receptor expression thus represent an additional parameter to basal receptor density expression. Different expression and inducibilities of activating receptors on NK cells contribute to the high diversity of NK cell populations and may help our understanding of the inter-individual differences in innate responses that underlie divergent disease courses.
    Frontiers in Immunology 07/2014; 5:305. DOI:10.3389/fimmu.2014.00305
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