Disease relevance of Killer Cells, Natural

• The strongest synergistic effect of these loci was on progression to depletion of CD4(+) T cells, which suggests that a protective response of NK cells involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1 infection [1].
• TWEAK-/- mice had overabundant natural killer (NK) cells and displayed hypersensitivity to bacterial endotoxin, with their innate immune cells producing excess interferon (IFN)-gamma and interleukin (IL)-12 [2].
• Sera from healthy persons did not contain a detectable level of sFasL, whereas those from patients with large granular lymphocytic (LGL) leukemia and natural killer (NK) cell lymphoma did [3].
• Specifically, the activity of natural killer (NK) cells, which are involved in the resistance to infections and metastasis, can be suppressed in the presence of ethanol in vitro [4].
• These findings indicate how NKp46-expressing NK cells may recognize target cells infected by influenza or parainfluenza without the decreased expression of target-cell MHC class I protein [5].

Psychiatry related information on Killer Cells, Natural

• RESULTS: Severe stress and depressive symptoms were independently related to decreases on immune measures from entry to 2-year follow-up, that is, declines in CD8+ T cells and CD56+ and CD16+ NK cell subsets [6].
• Differential effects of recombinant human interferon-gamma and interleukin 2 on natural killer cell activity of peripheral blood in early human development [7].
• RESULTS: Both patients with panic disorder and patients with social phobia had increased CD16 (natural killer) cell numbers [8].
• Alcohol consumption decreases IL-2-induced NF-kappaB activity in enriched NK cells from C57BL/6 mice [9].
• These results demonstrate that brief psychological stress is associated with some rapid immune cell changes, including release of CD8 suppressor/cytotoxic T cells and NK cells into circulation, and in young subjects, increases in NK activity [10].

High impact information on Killer Cells, Natural

• NATURAL KILLER CELL DEVELOPMENTAL PATHWAYS: A Question of Balance [11].
• Virtually all of the measurable cell-mediated cytotoxicity delivered by cytotoxic T lymphocytes and natural killer cells comes from either the granule exocytosis pathway or the Fas pathway [12].
• Their combinatorial expression creates a repertoire of NK cells that surveys the expression of almost every MHC molecule independently, thus antagonizing the spread of pathogens and tumors that subvert innate and adaptive defense by selectively downregulating certain MHC class I molecules [13].
• Certain CpG motifs (CpG-A) are especially potent at activating NK cells and inducing IFN-alpha production by PDCs, while other motifs (CpG-B) are especially potent B cell activators [14].
• A direct correlation exists between the surface density of NCR and the ability of NK cells to kill various tumors [15].

Chemical compound and disease context of Killer Cells, Natural

• Depletion of the NK cells in vivo with antiserum to asialo GM1 rendered both SCID and CB17 control mice much more sensitive to MCMV infection, as shown by titers of virus in organs and by survival curves [16].
• NKG2D-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules [17].
• The outcome of experimental metastasis of several tumors with defined biologic behavior was studied in syngeneic mice exhibiting low NK cell activity [3-wk-old normal mice and cyclophosphamide (Cy)-treated adult mice] and high NK cell activity (normal adult mice) [18].
• The splenic T-lymphocyte blastogenic and natural killer cell (NK) activities of C57BL/6 mice bearing cloned metastatic C3 or nonmetastatic C8 variants of the Lewis lung carcinoma were suppressed [19].
• Natural killer (NK) cells were assessed in patients with hyperthyroxinemia due to Graves' disease or treatment with thyroxine (T4) [20].

Biological context of Killer Cells, Natural

• On the plasma membrane of NK cells, TYROBP associates with activating receptors recognizing major histocompatibility complex (MHC) class I molecules [21].
• Ikaros proteins are required for normal T, B, and NK cell development and are postulated to activate lymphocyte-specific gene expression [22].
• Mice homozygous for a germline mutation in the Ikaros DNA-binding domain lack not only T and B lymphocytes and natural killer cells but also their earliest defined progenitors [23].
• Inducible cellular transformation by a metallothionein-ras hybrid oncogene leads to natural killer cell susceptibility [24].
• We have determined the sequence of the N-terminal amino acids of perforin purified from a mouse natural killer cell line, and, by using oligonucleotide probes corresponding to the amino acid residues, we have identified a complementary DNA encoding perforin from the cDNA library of a mouse cytotoxic T lymphocyte clone [25].

Anatomical context of Killer Cells, Natural

• Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function [26].
• Anti-CD43 monoclonal antibodies have a modest costimulatory effect on T cells, natural killer cells, B cells and monocytes, and one such antibody has been shown to activate T cells directly [27].
• Upon contact with a variety of tumor cells that are poorly recognized by NK cells, B220(+)NK1.1(+) dendritic cells secrete high levels of IFN-gamma and mediate TRAIL-dependent lysis of tumor cells [28].
• Perforin is one of the cytolytic factors present in the cytoplasmic granules of mouse cytotoxic T lymphocytes and natural killer cells [25].
• Activation of cytolytic T lymphocyte and natural killer cell function through the T11 sheep erythrocyte binding protein [29].

Associations of Killer Cells, Natural with chemical compounds

• Upon ligand binding and activation, the inhibitory NK cell receptors become tyrosine phosphorylated and recruit tyrosine phosphatases, SHP-1 and possibly SHP-2, resulting in inhibition of NK cell-mediated cytotoxicity and cytokine expression [30].
• In a subgroup of patients, the cytotoxicity of natural killer cells was lower in the pravastatin group than in the control group (9.8 percent vs. 22.2 percent specific lysis, P = 0.014) [31].
• Ethanol had no effect in rats selectively depleted of NK cells or when an NK-insensitive tumor (C4047) was used [4].
• Inhibition of the cyclooxygenase pathway with acetylsalicylic acid or indomethacin had minimal effects on NK cell activity [32].
• Agents inducing NK-cell maturation or activation such as polyinosinic-polycytidylic acid (poly(I:C], interferon (IFN) and interleukin-2 (IL-2) restore NK activity, and normalize the number of LGL [33].

Gene context of Killer Cells, Natural

• The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens [34].
• Natural killer cells predominantly express CX3CR1 and respond to fractalkine in both migration and adhesion [35].
• HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C [36].
• During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium [37].
• This review examines the pervasive effects of IL-2 and IL-15 on NK cell biology, with an emphasis on recent discoveries and lingering challenges in the field [38].

Analytical, diagnostic and therapeutic context of Killer Cells, Natural

• Notably, NK cells that are perforin competent are sufficient to restore allograft tolerance in perforin-deficient recipients [39].
• After donor antigen infusion, temporary NK-cell depletion and a 4-week administration of Leflunomide, hamster heart grafts survived even after withdrawal of immunosuppression [40].
• We then investigate how KIR ligation interrupts PTK-dependent NK cell activation signals [41].
• The intermediate affinity binding of NKIR to HLA-C, determined by alpha73 and alpha90, has an essential role in preventing cross-reactivity and ensuring the availability of NK cells for immunosurveillance; low affinity and high affinity mutants are both physiologically impaired [42].
• By adoptive transfer and complete Freund's adjuvant stimulation experiments, we demonstrated that L-selectin on NK cells and L-selectin ligands on endothelial cells are essential for NK cell recruitment to lymph nodes [43].

References