Disease relevance of Killer Cells

• Splenic killer cell phenotype in normal as well as all treated animals was ASGM1+, Thy-1-, and Lyt-2-. The combination therapy resulted in the strongest mononuclear cell infiltration in the lungs, with areas of young granulation tissue suggestive of repair sites of original metastases [1].
• At dosages of 20 mg clotrimazole/kg/d, all subjects showed Gardos channel inhibition, reduced erythrocyte dehydration, increased cell K+ content, and somewhat increased hemoglobin levels [2].
• These findings provide the first direct evidence that the infiltrating cells in the aortic tissue mainly consist of killer cells, and strongly suggest that these killer cells, especially gamma delta T lymphocytes, may recognize HSP-65 and play a critical role in the vascular cell injury of Takayasu's arteritis by releasing perforin [3].
• Glucose-dependent insulinotropic polypeptide (GIP) is a 42-amino acid peptide produced by K cells of the mammalian proximal small intestine and is a potent stimulant of insulin release in the presence of hyperglycemia [4].
• Modification of spleen cells from the strain or origin (129) of this teratoma line with trinitrobenzene sulfonic acid allows the generation of syngeneic killer cells that display a cytotoxic effect against trinitrophenyl-modified splenic targets, but not against trinitrophenyl-modified F9 targets [5].

High impact information on Killer Cells

• A transcript map of the region identified 19 genes, including members of the killer cell lectin-like receptor family a (Klra, formerly Ly49; refs. 9-12), which encode inhibitory or activating NK cell receptors that interact with MHC class I molecules [6].
• Here, a mechanism by which killer cells resist their own toxin is shown: internal toxin inhibits TOK1 channels and suppresses activation by external toxin [7].
• The human p58 natural killer-cell inhibitory receptor clone 42 recognizes HLA-Cw4, -Cw2 and -Cw6, but not HLA-Cw3, -Cw2, -Cw7 or -Cw8, which are recognized by p58 killer-cell inhibitor receptor clone 43 [8].
• ICAM-2 redistributed by ezrin as a target for killer cells [9].
• Interactions of such oligosaccharides on the target cell surface with NKR-P1 on the killer cell surface are crucial both for target cell recognition and for delivery of stimulatory or inhibitory signals linked to the NK cytolytic machinery [10].

Chemical compound and disease context of Killer Cells

• Differentiation of melanoma cells with dimethyl sulfoxide, retinoic acid, and theophylline resulted in a marked and selective increase in the amount of Leo Mel 3-defined antigen, together with an increase in the target cell binding ability of these cells, assessed by cold target competition assays using anomalous killer cells [11].
• Target blocking by anti-HTLV-1-related Ag suggested that the target molecules recognized by the specific killer cells may be virus envelope glycoprotein gp 68 and other cellular Ag induced by HTLV-1 infection [12].
• Perforin-mediated lysis of tumor cells by Mycobacterium bovis Bacillus Calmette-Guérin-activated killer cells [13].
• The lymphoid K cell, detectable in rat spleen and blood, was unaffected by steroid treatment sufficient to cause lymphopenia, whereas splenic anti-chicken erythrocyte cytotoxicity of whole spleen and of phagocyte-free spleen was depressed in mice and rats [14].
• IFN, 2',5'-oligoadenylate (2',5'-A) synthetase (an IFN-induced enzyme), T and natural killer cell subsets, and natural and anomalous killer cell functions were studied systemically during acute infectious mononucleosis [15].

Biological context of Killer Cells

• Recognition of major histocompatibility (MHC) class I complexes on target cells by killer cell inhibitory receptors (KIR) blocks natural killer (NK) and T cell cytotoxic function [16].
• Such characteristic cytotoxic spectra, as well as serological phenotypes (Thy-1+, Lyt-1-2-, asialo GM1-positive, T200+, TdT-, Fc receptor-positive) indicated that these LGL clones exactly represent endogenous NK cells, rather than a variety of anomalous killer cells generated in various culture conditions [17].
• This ADCC was inhibited by an anti-FcRlow (CD16) monoclonal antibody, which suggests that these effectors were K-cells [18].
• Natural killer (NK) cells express killer cell inhibitory receptors (KIRs) for major histocompatibility complex class I molecules [19].
• Unlike the plant inward-rectifying guard cell K+ channels KAT1 and KST1, the AKT3 channels were only weakly regulated by the membrane potential [20].

Anatomical context of Killer Cells

• Although it is structurally related to human killer cell inhibitory receptors, LAIR-1 does not appear to recognize human leukocyte antigen (HLA) class I molecules and thus represents a novel HLA class I-independent mechanism of NK cell regulation [21].
• The HNK-1 antibody known to define a subpopulation of human lymphocytes with natural killer and killer cell activities was shown to detect a common neuroectodermal antigen [22].
• TLiSA1, a human T lineage-specific activation antigen involved in the differentiation of cytotoxic T lymphocytes and anomalous killer cells from their precursors [23].
• We also show that the enhanced killing is due to both UL18-dependent and -independent mechanisms, and that the killer cell inhibitory receptors (KIRs) and CD94/NKG2A inhibitory receptors for MHC class I do not play a role in affecting susceptibility of CMV-infected fibroblasts to NK cell-mediated cytotoxicity [24].
• Since killer-specific esterases and channel-forming proteins can be demonstrated in in vitro cell lines, it is important to ascertain that the described esterase and channel-forming proteins are also present in killer cells from in vivo sources [25].

Associations of Killer Cells with chemical compounds

• Glucose-dependent insulin release from genetically engineered K cells [26].
• Recruitment of tyrosine phosphatase HCP by the killer cell inhibitor receptor [27].
• Retinoic acid increased splenic K-cell activity, already elevated in aged mice and unaffected by the other two agents [28].
• Neuraminidase-augmented anticarcinoembryonic antigen (CEA)-complement lysis of human colon tumor cells: lack of correlation with anti-CEA-mediated K-cell lysis and iodine-125 binding [29].
• This recovery of cell K+ content was inhibited, in an additive manner, by quinine and furosemide [30].

Gene context of Killer Cells

• Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer [31].
• We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to its class I MHC ligand, HLA-Cw4 [32].
• NKB1 is one member of a growing family of killer cell inhibitory receptors (KIR) [33].
• HLA-E had no apparent inhibitory effect mediated through the identified Ig superfamily (Ig-SF) human killer cell inhibitory receptors or ILT2/LIR1 [34].
• CONCLUSIONS: Our findings strongly suggest that expression of B7-1, B7-2, and CD40 antigens on cardiac myocytes may make them APCs for CTLs and NK cells and that they may play an important role in the direct myocardial damage by these killer cells in acute myocarditis and DCM [35].

Analytical, diagnostic and therapeutic context of Killer Cells

• Southern blot analysis with a probe specific for genes encoding the beta chain of the T cell receptor on T helper and T killer cells revealed no rearrangement of the beta genes in the Ts cells [36].
• Immunotherapy with anti-CD3 monoclonal antibodies and recombinant interleukin 2: stimulation of molecular programs of cytotoxic killer cells and induction of tumor regression [37].
• Adoptive cellular immunotherapy, infusions of interleukin 2 (IL-2) in conjunction with in vitro-activated killer cells, has brought new hope to patients with cancer [37].
• The replacement of FP with recombinant GM-CSF as an immunostimulant completely abrogated the selection of RCC-specific killer cells in peripheral blood mononuclear cell cultures [38].
• Molecular cloning of a novel murine cell-surface glycoprotein homologous to killer cell inhibitory receptors [39].

References