1,162 research outputs found
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No full textS Ahlawat, P Sharma R Sharma, R Arora, NK Verma, B Brahma, P Mishra and S De (2016) Evidence of positive selection and concerted evolution in the rapidly evolving PRDM9 zinc finger domain in goats and sheep. Animal Genetics, DOI: 10.1111/age12487.Not AvailableNot Availabl
Development of antibody technology to identify natural killer cell surface antigens in Xenopus Laevis
No full textNatural killer (NK)-like lymphocytes have recently been identified in thymectomised (Tx) Xenopus which are capable of spontaneous cytotoxicity towards the MHC- deficient, allogeneic thymus tumour cell line B(_3)B(_7). This Thesis describes attempts to raise antibodies to Xenopus NK cell surface antigens by phage display and hybridoma technology. The phage display technique was optimised for raising antibodies to novel, cellular antigens in a trial run using the Xenopus thymus tumour cell line B(_3)B(_7). Having isolated a phage antibody which was shown by flow cytometry to bind B(_3)B(_7) cells, the technique was then used to try and raise antibodies to Xenopus NK cells. Isolation of an NIC-specific phage antibody was not achieved but phage antibody XL-6 was raised, which bound an antigen on Xenopus lymphocytes. Phage antibody XL-6, and soluble scFv derived from this, were able to identify a putative mature T cell population in the thymus and may be specific for an amphibian homologue of the mammalian leukocyte common antigen CD45. Hybridoma technology was used to isolate three monoclonal antibodies, 1F8, 4D4 and 1G5, which were shown by flow cytometric analysis to identify a putative NK cell population in control and Tx Xenopus. Following immunomagnetic purification, 1F8- positive spleen cells from control and Tx animals were shown to kill the MHC- deficient tumour target B(_3)B(_7), confirming that this antibody was specific for Xenopus NK cells. Western blotting experiments showed that 1F8, 4D4 and 1G5 identified a doublet of protein bands at 72 and 74 kilodaltons in Xenopus gut lymphoid lysates. Initial attempts to isolate cDNA encoding a Xenopus NK cell surface antigen through immunoscreening a xenopus gut cDNA expression library with antibody 1G5 were unsuccessful as was an attempt to clone a Xenopus homologue of the mammalian NK receptor NKR-Pl by PGR
Visual acuity correlates with multimodal imaging-based categories of central serous chorioretinopathy
No full textObjective: To evaluate visual acuity (VA) and factors influencing VA using new multimodal imaging-based classification of central serous chorioretinopathy (CSCR).
Methods: Retrospective, observational and cross-sectional study on 229 naïve eyes diagnosed as CSCR with available baseline data and multimodal imaging. Each case was classified into (i) simple/complex/atypical; (ii) primary/recurrent/resolved; (iii) persistent or not; (iv) outer retinal atrophy(ORA) present/absent; (v) foveal involvement present/absent; and (vi) macular neovascularization(MNV) present/absent. Best corrected visual acuity (BCVA) was correlated to the classification as well as every parameter of the classification.
Results: Median BCVA was 0.18 logMAR [95% Confidence Interval (CI)0.16-0.18] with median duration of complaints of one month (95% CI,6.14-13.0 months). Age of the patient (r = -0.24, p = 0.002) and duration of the disease (r = -0.32, p < 0.001) correlated significantly with BCVA. Logistic regression model showed that older age [odds ratio (OR) = 0.96, p = 0.05], female gender (OR = 2.45, p = 0.046), presence of ORA(OR = 0.34, p = 0.012),and foveal involvement(OR = 0.18, p = 0.007) were statistically significantly associated with poorer BCVA. Eyes classified as complex, persistent CSCR, with ORA or foveal involvement demonstrated lower BCVA compared to those with simple, non-persistent CSCR, without ORA or without foveal involvement (p < 0.05). Eyes with complex CSCR (p < 0.001), atypical CSCR(p = 0.025), persistent subretinal fluid (SRF) (p = 0.001) and those with ORA (p < 0.001) demonstrated a trend towards severe visual loss. Prevalence of persistent SRF, recurrent episodes and ORA was significantly higher among eyes with complex CSCR (p < 0.001) while there was no difference in prevalence of resolved cases (p = 0.07), foveal involvement (p = 0.28) and MNV (p = 0.45) between simple and complex cases.
Conclusion: There is a strong correlation between VA and foveal involvement and ORA using the new classification. Thus, the objective parameters of the classification can be incorporated in establishing the treatment guidelines for CSCR
The Adhesion G Protein-Coupled Receptor GPR56/ADGRG1 Is an Inhibitory Receptor on Human NK Cells
No full textSummaryNatural killer (NK) cells possess potent cytotoxic mechanisms that need to be tightly controlled. Here, we explored the regulation and function of GPR56/ADGRG1, an adhesion G protein-coupled receptor implicated in developmental processes and expressed distinctively in mature NK cells. Expression of GPR56 was triggered by Hobit (a homolog of Blimp-1 in T cells) and declined upon cell activation. Through studying NK cells from polymicrogyria patients with disease-causing mutations in ADGRG1, encoding GPR56, and NK-92 cells ectopically expressing the receptor, we found that GPR56 negatively regulates immediate effector functions, including production of inflammatory cytokines and cytolytic proteins, degranulation, and target cell killing. GPR56 pursues this activity by associating with the tetraspanin CD81. We conclude that GPR56 inhibits natural cytotoxicity of human NK cells
[Portion of America] [cartographic material].
No full textSection of a map of America with relief shown pictorially.; Title and author information taken from pencil notes on verso of map.; Rex Nan Kivell Collection Map NK 10432
Trans-endocytosis of intact IL-15Rα–IL-15 complex from presenting cells into NK cells favors signaling for proliferation
No full textInterleukin 15 (IL-15) is essential for natural killer (NK) cell survival and proliferation. The IL-15 receptor consists of 3 subunits: the α chain and the β and common γ chains, which are shared with the IL-2 receptor. NK cells express the β-γchains and are activated in trans by cells presenting IL-15 bound to IL-15Rα, such as dendritic cells. We show here that the release of soluble IL-15Rα–IL-15 complex from presenting cells contributes to efficient signaling for NK cell survival, whereas uptake of the entire membrane-associated-IL-15Rα–IL-15 complex from presenting cells into NK cells contributes to proliferation. Thus, outcomes are dictated not only by signal strength, but also by location where IL-15 trans-presentation occurs in NK cells.National Institute of Health (USA)National Institute of Allergy and Infectious Diseases (USA)National Cancer Institute (USA)Depto. de Bioquímica y Biología MolecularFac. de Ciencias QuímicasTRUEpu
In Vivo IFN-γ Secretion by NK Cells in Response to Salmonella Typhimurium Requires NLRC4 Inflammasomes
No full textabstract: Natural killer (NK) cells are a critical part of the innate immune defense against viral infections and for the control of tumors. Much less is known about how NK cells contribute to anti-bacterial immunity. NK cell-produced interferon gamma (IFN-γ) contributes to the control of early exponential replication of bacterial pathogens, however the regulation of these events remains poorly resolved. Using a mouse model of invasive Salmonellosis, here we report that the activation of the intracellular danger sensor NLRC4 by Salmonella-derived flagellin within CD11c[superscript +] cells regulates early IFN-γ secretion by NK cells through the provision of interleukin 18 (IL-18), independently of Toll-like receptor (TLR)-signaling. Although IL18-signalling deficient NK cells improved host protection during S. Typhimurium infection, this increased resistance was inferior to that provided by wild-type NK cells. These findings suggest that although NLRC4 inflammasome-driven secretion of IL18 serves as a potent activator of NK cell mediated IFN-γ secretion, IL18-independent NK cell-mediated mechanisms of IFN-γ secretion contribute to in vivo control of Salmonella replication.The article is published at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.009741
HCMV vCXCL1 Binds Several Chemokine Receptors and Preferentially Attracts Neutrophils over NK Cells by Interacting with CXCR2
No full textSummaryHCMV is a highly sophisticated virus that has developed various mechanisms for immune evasion and viral dissemination throughout the body (partially mediated by neutrophils). NK cells play an important role in elimination of HCMV-infected cells. Both neutrophils and NK cells utilize similar sets of chemokine receptors to traffic, to and from, various organs. However, the mechanisms by which HCMV attracts neutrophils and not NK cells are largely unknown. Here, we show a unique viral protein, vCXCL1, which targets three chemokine receptors: CXCR1 and CXCR2 expressed on neutrophils and CXCR1 and CX3CR1 expressed on NK cells. Although vCXCL1 attracted both cell types, neutrophils migrated faster and more efficiently than NK cells through the binding of CXCR2. Therefore, we propose that HCMV has developed vCXCL1 to orchestrate its rapid systemic dissemination through preferential attraction of neutrophils and uses alternative mechanisms to counteract the later attraction of NK cells
NK cell immunesenescence is increased by psychological but not physical stress in older adults associated with raised cortisol and reduced perforin expression
No full textNK cell cytotoxicity (NKCC) reduces with age and this has been associated previously with increased mortality. The immune response is also modulated by stress, and here, we assessed the effect of the physical stress of hip fracture and the psychological stress of depression on NKCC in an aged immune system. NKCC was assessed in 101 hip fracture patients (81 female) 6 weeks and 6 months after injury and in 50 healthy age-matched controls (28 female). Thirty-eight patients were depressed at 6 weeks post-injury, and NKCC was reduced in patients who developed depression compared with non-depressed hip fracture patients (p = 0.004) or controls (p < 0.02). NKCC remained lower in the depressed patients compared to those without depression 6 months post-fracture (p = 0.017). We found reduced expression of perforin in NK cells of depressed hip fracture patients compared with controls at 6 weeks (p = 0.001) post-fracture. Serum cortisol levels were also elevated in patients with depression compared to non-depressed patients at 6 weeks (p = 0.01) and 6 months (p = 0.05). NK cells treated with dexamethasone showed a concentration-dependent reduction in NKCC and perforin expression. We propose that depression is the major factor affecting NK cell immunity after hip fracture
HIV-1 Control by NK Cells via Reduced Interaction between KIR2DL2 and HLA-C∗12:02/C∗14:03
No full textSummaryNatural killer (NK) cells control viral infection in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands. We investigated 504 anti-retroviral (ART)-free Japanese patients chronically infected with HIV-1 and identified two KIR/HLA combinations, KIR2DL2/HLA-C∗12:02 and KIR2DL2/HLA-C∗14:03, that impact suppression of HIV-1 replication. KIR2DL2+ NK cells suppressed viral replication in HLA-C∗14:03+ or HLA-C∗12:02+ cells to a significantly greater extent than did KIR2DL2− NK cells in vitro. Functional analysis showed that the binding between HIV-1-derived peptide and HLA-C∗14:03 or HLA-C∗12:02 influenced KIR2DL2+ NK cell activity through reduced expression of the peptide-HLA (pHLA) complex on the cell surface (i.e., reduced KIR2DL2 ligand expression), rather than through reduced binding affinity of KIR2DL2 to the respective pHLA complexes. Thus, KIR2DL2/HLA-C∗12:02 and KIR2DL2/HLA-C∗14:03 compound genotypes have protective effects on control of HIV-1 through a mechanism involving KIR2DL2-mediated NK cell recognition of virus-infected cells, providing additional understanding of NK cells in HIV-1 infection
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