Natural killer cells: Walking three paths down memory lane

University of California, San Francisco, San Francisco, California, United States
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.

Download full-text


Available from: Yosuke Kamimura, Jun 05, 2014
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Jun 2015 · Cellular Immunology
  • Source
    • "Accumulating evidence now support that NK cells possess properties previously attributed to the adaptive immune system. Long-lived NK cells differentiate following viral infection; they exhibit functions that recall those of memory lymphocytes(reviewed in [159]. DNAM-1 was recently shown to play a critical role in the generation of memory NK cells following MCMV infection[160]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Natural killer (NK) cells constitute a population of lymphocytes involved in innate immune functions, they play a critical role in anti-viral immune surveillance. Viruses have evolved with their host species for millions of years, each exerting a selective pressure upon the other. As a corollary, the pathways used by the immune system that are critical to control viral infection can be revealed by defining the role of viral gene products that are non-essential for virus replication. We relate here the battery of resources available to NK cells to recognize and eliminate viruses and reciprocally the immune evasion mechanisms developed by viruses to prevent NK cell activation.
    Full-text · Article · Feb 2015 · Future Virology
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Preview · Article · Nov 2014 · Journal of Experimental Medicine
Show more