Human natural killer cells in health and disease

Department of Pediatrics, Columbia University, New York, New York, United States
Pediatric Blood & Cancer (Impact Factor: 2.39). 10/2007; 49(5):615-23. DOI: 10.1002/pbc.21158
Source: PubMed


Natural killer (NK) cells are an essential component of the innate immune system and play a critical role in tumor immune surveillance. NK cells express their own repertoire of receptors (NKRs) that bind to major histocompatibility class I or class I-like molecules. The balance of signals from stimulation or inhibition of NKRs determines the ability of NK cells to lyse specific targets. In haploidentical stem cell transplantation with purified stem cells, NK cell alloreactivity (killer immunoglobulin-like receptor [KIR] mismatch) has been demonstrated to reduce the risk of relapse in acute myeloid leukemia. There is a need for adequately powered prospective randomized studies to determine the usefulness of NK cells as adoptive immunotherapy, optimal NK cell doses and timing of administration. Further studies are required to determine optimal selection of donors and recipients, both on NKR matching/mismatching, undergoing haploidentical and unrelated hematopoetic stem cell transplantation.

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Available from: Evan Shereck, Oct 24, 2014
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    • "The phenotype of NKs is defined as CD3 − , CD16 + , and CD56 + . Basically, NK cells protect the host by eliminating the invasion of microorganisms and also inhibiting the process of malignant transformation; thus, the cytotoxicity of NKs should be kept in a normal range [8] [9]. The lower NK cytotoxicity has been connected to the severity of several diseases, such as chronic fatigue immune dysfunction syndrome [10], atherosclerosis [11], myeloproliferative disorders [12], and obsessive-compulsive disorder [13]. "
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    ABSTRACT: A personalized probiotic microfluidic chip system has been established and used to screen the probiotics which had the highest value of IFN-íµí»¾/IL-10 or IL-10/IFN-íµí»¾ among six probiotics, including L. paracasei BRAP01, L. acidophilus AD300, B. longum BA100, E. faecium BR0085, L. rhamnosus AD500, and L. reuteri BR101. One hundred volunteers were included and their PBMCs were collected and stimulated by the six probiotics. People who belonged to the IFN-íµí»¾ group took the probiotics that exerted the highest ratio of IFN-íµí»¾/IL-10 and vice versa in IL-10 group. A significant increase in NK cytotoxicity of 69 volunteers in the IFN-íµí»¾ group was observed compared to the IL-10 group (íµí±› = 21) and control group (íµí±› = 10). The result also showed that L. paracasei BRAP01 and L. acidophilus AD300 were the two dominant inducers in IFN-íµí»¾ group which yielded higher value of IFN-íµí»¾/IL-10 than the other 4 probiotics, while L. reuteri BR101 was the most effective agent on the ratio of IL-10/IFN-íµí»¾ in the IL-10 group. Our finding highlighted the concept of personalized probiotics and also provided a good foundation to investigate the probiotics with NK activity.
    Journal of Immunology Research 11/2014; 2014(2). DOI:10.1155/2014/721505 · 2.93 Impact Factor
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    • "In type 1 inflammatory immune responses including atherosclerosis and acute phase of MI, IFN-γ is known to play a major role in activating monocytes and macrophages (Boehm et al., 1997; Schroder et al., 2004) and driving them toward inflammatory phenotype (e.g., M1 macrophages or Ly6C hi monocytes) (Abbas et al., 1996). NK cells are key players in the innate immune response and produce a variety of cytokines such as IL-1beta, tumor necrosis factor alpha (TNFα), and IFN-γ and thereby participate in regulating innate and adaptive immunity (Yokoyama et al., 2004; Shereck et al., 2007). They represent a specialized lymphoid population , and act in an activating and inhibiting way by expressing different receptors (Moretta and Moretta, 2004). "
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    ABSTRACT: Inflammatory monocytes and macrophages have been identified as key players in the pathogenesis of atherosclerosis, arterial hypertension, and myocardial infarction (MI). They become powerful mediators of vascular inflammation through their capacity to secrete and induce the production of proinflammatory cytokines, chemokines and adhesion molecules and through the production of reactive oxygen species mainly via their NADPH oxidase. Importantly, a crosstalk exists between NK cells and monocytes that works via a feedforwad amplification loop of T-bet/Interferon-gamma/interleukin-12 signaling, that causes mutual activation of both NK cells and monocytes and that fosters recruitment of inflammatory cells to sites of inflammation. Recently, we have discovered that this crosstalk is crucial for the unrestricted development of angiotensin II (ATII) induced vascular injury in arterial hypertension, the most important risk factor for atherosclerosis and cardiovascular disease worldwide. In this review, we will also discuss possible implications of this interplay between NK cells and monocytes for the pathogenesis of coronary atherosclerosis and myocardial infarction and potential therapeutic options.
    Frontiers in Physiology 08/2014; 5:295. DOI:10.3389/fphys.2014.00295 · 3.53 Impact Factor
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    • "NK cells express specific receptors (NK1.1, NKG2D in mice; NKp46, CD56, and CD57 in humans) and produce large amounts of perforin and granzyme B in addition to immunomodulatory factors such as interferon gamma (IFNγ) and TNFα upon activation [42] [43]. NK cells are particularly responsive to malignant or infected cells while also potentially contributing to transplant rejection and autoimmunity [44] [45]. "
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    ABSTRACT: Emerging evidence suggests a strong interaction between the gut microbiota and health and disease. The interactions of the gut microbiota and the liver have only recently been investigated in detail. Receiving approximately 70% of its blood supply from the intestinal venous outflow, the liver represents the first line of defense against gut-derived antigens and is equipped with a broad array of immune cells (i.e., macrophages, lymphocytes, natural killer cells, and dendritic cells) to accomplish this function. In the setting of tissue injury, whereby the liver is otherwise damaged (e.g., viral infection, toxin exposure, ischemic tissue damage, etc.), these same immune cell populations and their interactions with the infiltrating gut bacteria likely contribute to and promote these pathologies. The following paper will highlight recent studies investigating the relationship between the gut microbiota, liver biology, and pathobiology. Defining these connections will likely provide new targets for therapy or prevention of a wide variety of acute and chronic liver pathologies.
    Gastroenterology Research and Practice 07/2010; 2010(1687-6121). DOI:10.1155/2010/453563 · 1.75 Impact Factor
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