In the context of kidney transplantation, little is known about the involvement of natural killer (NK) cells in the immune reaction leading to either rejection or immunological tolerance under immunosuppression. Therefore, the peripheral NK cell repertoire of patients after kidney transplantation was investigated in order to identify NK cell subsets that may be associated with the individual immune status at the time of their protocol biopsies for histopathological evaluation of the graft. Alterations in the peripheral NK cell repertoire could be correlated to the type of immunosuppression, i.e., calcineurin-inhibitors like Cyclosporin A vs. Tacrolimus with or without addition of mTOR inhibitors. Here, we could demonstrate that the NK cell repertoire in peripheral blood of kidney transplant patients differs significantly from healthy individuals. The presence of donor-specific antibodies was associated with reduced numbers of CD56dim NK cells. Moreover, in patients, down-modulation of CD16 and CD6 on

Insufficient natural killer cell responses against retroviruses: how to improve NK cell killing of retrovirus-infected cells. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

Sharma, S D.; Tsai, V; and Proffitt, M R., Enhancement of mouse natural killer cell activity by thyroxine. (1982). Subject Strain Bibliography 1982. 1180 ...

TY - JOUR. T1 - In vivo reactivity of mouse natural killer (NK) cells against normal bone marrow cells. AU - Riccardi, C.. AU - Santoni, A.. AU - Barlozzari, T.. AU - Herberman, R. B.. PY - 1981/5/1. Y1 - 1981/5/1. N2 - An in vivo role for mouse natural killer (NK) cells in the rapid rejection of transplantable tumors has been previously demonstrated, using an assay of elimination of [125I]iododeoxyuridine-labeled tumor cells from the lungs and other organs. We have now used the same technique to examine the role of NK cells in in vivo clearance of syngeneic or allogeneic bone marrow cells from normal mice. The degree of clearance from the lungs or liver, at 4 hr after intravenous inoculation of radiolabeled bone marrow cells, correlated with the levels of NK activity in the recipients. Young CBA mice, with high NK activity, showed substantially more clearance of bone marrow cells than SJL mice, with low NK activity. Within the same strain, mice at 7 weeks of age had higher in vivo as well as in ...

TY - JOUR. T1 - Stage-dependent gene expression profiles during natural killer cell development. AU - Kang, Hyung Sik. AU - Kim, Eun Mi. AU - Lee, Sanggyu. AU - Yoon, Suk Ran. AU - Kawamura, Toshihiko. AU - Lee, Young Cheol. AU - Kim, Sangsoo. AU - Myung, Pyung Keun. AU - San, Ming Wang. AU - Choi, Inpyo. PY - 2005/11/1. Y1 - 2005/11/1. N2 - Natural killer (NK) cells develop from hematopoietic stem cells (HSCs) in the bone marrow. To understand the molecular regulation of NK cell development, serial analysis of gene expression (SAGE) was applied to HSCs, NK precursor (pNK) cells, and mature NK cells (mNK) cultured without or with OP9 stromal cells. From 170,464 total individual tags from four SAGE libraries, 35,385 unique genes were identified. A set of genes was expressed in a stage-specific manner: 15 genes in HSCs, 30 genes in pNK cells, and 27 genes in mNK cells. Among them, lipoprotein lipase induced NK cell maturation and cytotoxic activity. Identification of genome-wide profiles of gene ...

Abstract Natural killer (NK) cells are considered to be critical players in anticancer immunity. However, cancers are able to develop mechanisms to escape NK cell attack or to induce defective NK cells. Current NK cell-based cancer immunotherapy is aimed at overcoming NK cell paralysis through several potential approaches, including activating autologous NK cells, expanding allogeneic NK cells, usage of stable allogeneic NK cell lines and genetically modifying fresh NK cells or NK cell lines. The stable allogeneic NK cell line approach is more practical for quality-control and large-scale production. Additionally, genetically modifying NK cell lines by increasing their expression of cytokines and engineering chimeric tumor antigen receptors could improve their specificity and cytotoxicity. In this review, NK cells in tumor immunotherapy are discussed, and a list of therapeutic NK cell lines currently undergoing preclinical and clinical trials of several kinds of tumors are reviewed.. ...

CHAPTER 85 FUNCTIONS OF NATURAL KILLER CELLS Williams Hematology CHAPTER 85 FUNCTIONS OF NATURAL KILLER CELLS GIORGIO TRINCHIERI LEWIS L. LANIER Identification and Definition of Natural Killer Cells Definition Morphology Origin and Tissue Distribution Mechanisms of Natural Killer Cell Functions Cell-Mediated Cytotoxicity Production of Cytokines Physiologic Roles of Natural Killer Cells Natural Resistance Regulation of…

Now, results from a new study carried out using a mouse model, show that modified cells called super natural killer cells are able to seek out cancer cells in lymph nodes to destroy them, thus halting the process of metastasis. Michael King, senior author of the study, said in a press release: We want to see lymph node metastasis become a thing of the past.. The super natural killer cells find the cancerous cells in the lymph nodes and induce apoptosis - in other words, the cancer cells self-destruct and disintegrate, thus averting their further lymphatic spread. But what are these super natural killer cells? They are a modified version of the so-called natural killer cells - or NK cells for short.. NK cells are a type of lymphocytes that play a major role in the killing of cancer cells and virus-infected cells by inducing apoptosis. To obtain the super version of these lymphocytes, scientists attached nanoparticles to the NK cell surface. These nanoparticles contain a protein dubbed TRAIL ...

This sensitivity allows natural killer cells to vigorously initiate natural killer cytotoxicity (by emptying granules of porforin and granzyme) and inflammation as soon as pathogenesis is detected, and is essential to protection against viruses and tumors. Natural killer cells have genomic (not needed recombination, or RAG-independent) cell surface receptors which recognize classical Class I MHC molecules (and structural relatives like MICA, RAE-1 and H-60).. Natural killer cells lack TcRs, CD4s and CD8; instead, they have: cell-surface activating receptors, which bind noncovalently to molecules with ITAMs; and on the cytoplasmic side, inhibitory receptors with ITIM(s) which -- upon phosphorylation -- recruit and activate SHP-1 & -2, which inhibit the activating receptors. The balance between activating signals and inhibitory signals is what determines whether a natural killer cell will destroy or bypass a microbe it encounters. ...

TY - JOUR. T1 - Monocyte- and natural killer cell-mediated spontaneous cytotoxicity against human noncultured solid tumor cells. AU - Itoh, Kyogo. AU - Platsoucas, Chris D.. AU - Balch, Charles M.. PY - 1987. Y1 - 1987. N2 - Unstimulated human peripheral blood mononuclear cells from healthy donors exhibited spontaneous cytotoxicity against noncultured solid tumor targets in a 12- to 24-hr 51Cr release or 111In release assay. Both purified monocytes (, 99% monocytes) and natural killer (NK)-enriched lymphocytes exhibited comparable levels of spontaneous cytotoxicity against fresh melanoma tumor targets. This cytotoxicity was observed under endotoxin-free conditions. NK-depleted lymphocytes did not lyse the melanoma targets. Culture supernatants of monocytes incubated with the melanoma tumor cells did not exhibit cytotoxic activity against these targets. Purified monocytes lacked NK activity against the K562 targets in a 4-hr 51Cr release assay. Treatment of the monocytes with anti-Leu 11b and ...

Definition of Natural killer cells in the Legal Dictionary - by Free online English dictionary and encyclopedia. What is Natural killer cells? Meaning of Natural killer cells as a legal term. What does Natural killer cells mean in law?

TY - JOUR. T1 - Expression of CD94 and 56bright on Natural Killer Lymphocytes - the Influence of Exercise. AU - Horn, Peggy. AU - Leeman, K. AU - Gore, Christopher. PY - 2002. Y1 - 2002. M3 - Article. VL - 23. SP - 595. EP - 599. JO - International Journal of Sports Medicine. JF - International Journal of Sports Medicine. SN - 0172-4622. IS - 8. ER - ...

TY - JOUR. T1 - Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering. AU - Ayello, Janet. AU - van de Ven, Carmella. AU - Fortino, Weiwei. AU - Wade-Harris, Cheryl. AU - Satwani, Prakash. AU - Baxi, Laxmi. AU - Simpson, Lynn L.. AU - Sanger, Warren G. AU - Pickering, Diana. AU - Kurtzberg, Joanne. AU - Cairo, Mitchell S.. PY - 2006/6/1. Y1 - 2006/6/1. N2 - Cord blood (CB) natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic cells are poorly characterized but might be used to treat minimal residual and/or recurrent malignant disease. Currently, there is no mechanism to use CB for adoptive cancer cellular immunotherapy after CB transplantation (CBT). Recognizing this as a deficiency, we hypothesized that CB aliquots could be engineered ex vivo for potential donor lymphocyte infusion after CBT. Cryopreserved CB aliquots were thawed, depleted of monocytes, and cultured in serum-free medium alone or serum-free ...

Natural Killer Cells are the most aggressive white cells in the immune system. They make up about 5% to 15% of the total lymphocyte circulating population. They target tumor cell and protect against a wide variety of infectious microbes. Natural Killer Cells are a very important factor in the fight against cancer. Immune Stimulation is the key to keeping the white blood cell count high and giving the Natural Killer Cells a chance to fight cancer and other diseases.. ...

NK cell lytic activity is often inhibited by MHC class I molecules expressed by target cells. It is believed that this mechanism allows the immune system to destroy cells that downregulate class I expression due to infection or transformation ((1)). Most or all natural killer cells in mice express one or more members of the Ly49 receptor family, a group of closely related and genetically linked MHC class I-specific inhibitory receptors ((2)). The capacity of NK cells to attack target cells that lack MHC class I expression, while sparing cells that express self-MHC class I molecules, depends in large part on inhibitory recognition of MHC molecules by Ly49 receptors.. mAb reagents to some Ly49 receptors have been used to show that they are expressed on overlapping subsets of natural killer cells ((3)-(5)). An NK cell can express multiple Ly49 receptors, including Ly49 receptors that do not recognize self-MHC class I molecules. The overall pattern of expression of different Ly49 receptors suggests ...

Natural killer (NK) cells are innate immune cells that show strong cytolytic function against physiologically stressed cells such as tumor cells and virus-infected cells. NK cells show a broad array of tissue distribution and phenotypic variability. NK cells express several activating and inhibitory receptors that recognize the altered expression of proteins on target cells and control the cytolytic function. NK cells have been used in several clinical trials to control tumor growth. However, the results are encouraging only in hematological malignancies but not very promising in solid tumors. Increasing evidence suggests that tumor microenvironment regulate the phenotype and function of NK cells. In this review, we discussed the NK cell phenotypes and its effector function and impact of the tumor microenvironment on effector and cytolytic function of NK cells. We also summarized various NK cell-based immunotherapeutic strategies used in the past, and the possibilities to improve the function of NK cell

Background: A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8(+) T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings: In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any ...

Background A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8+ T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any further

TY - JOUR. T1 - Adhesion and activation molecules expressed by human natural killer cells. AU - Santoni, Angela. AU - Gismondi, Angela. AU - Paolini, Rossella. AU - Procopio, Antonio. AU - Morrone, Stefania. AU - Mainiero, Fabrizio. AU - Santoni, Giorgio. AU - Piccoli, Mario. AU - Frati, Luigi. PY - 1991/2. Y1 - 1991/2. N2 - Our study concerns the expression and the regulation of adhesion and activation receptors on human NK cells. In particular we provide evidence on: a) the expression on fresh human NK cells of VLA-4, VLA-5 and VLA-6, extracellular matrix (ECM) receptors of integrin family capable of mediating their adhesion to FN and LM; b) the role of PKC on the regulation of CD16, a differentiation antigen associated with FcγR type III expressed by all NK cells, which mediate ADCC activity and trigger lymphokine production.. AB - Our study concerns the expression and the regulation of adhesion and activation receptors on human NK cells. In particular we provide evidence on: a) the ...

Ulm C, Saffarzadeh M, Mahavadi P, Müller S, Prem G, Saboor F, Simon P, Middendorff R, Geyer H, Henneke I, Bayer N, Rinné S, Lütteke T, Böttcher-Friebertshäuser E, Gerardy-Schahn R, Schwarzer D, Mühlenhoff M, Preissner KT, Günther A, Geyer R, Galuska SP., Cell Mol Life Sci 70(19), 2013 ...

Hence, the hypothesis that UL18 replaces class I MHC molecules to prevent NK cell lysis does not seem to apply to hCMV-infected HFFs and transfected epithelial and ovary cells (293, COS-7, and CHO-K1). It was recently reported that UL18 inhibits NK cell lysis of 721.221 B lymphoblastoid targets, mediated through CD94 ((11)). In repeated studies, we never observed inhibition of NK cell killing against UL18 expressing targets using clones with functional CD94 or KIR. In view of this discrepancy, several aspects of the previous report should be highlighted. First, in the prior study UL18 was transfected into 721.221 targets; however, transfectants were isolated on the basis of surface β2M expression, not UL18. Second, we have failed to generate stable UL18 transfectants in 721.221 or in 15 other human or mouse lines, because it seems that prolonged expression (,2 wk) of UL18 results in cell death. We could only generate UL18 transfectants in high efficiency transient transfection systems such as ...

Brunda, M J.; Taramelli, D; Holden, H T.; and Varesio, L, Effects of resting and activated macrophages on natural killer cell activity and lymphoproliferation. Abstr. (1981). Subject Strain Bibliography 1981. 551 ...

A low affinity receptor for IgG immune complexes, Fc gamma RIII(CD16), is expressed on human NK cells as an integral membrane glycoprotein anchored through a tr

In a longterm study, we have divided coeliac disease into two distinct entities (abortive and permanent) based on the occurrence of large granular lymphocytes and natural killer cells within the epithelium of the gut. The natural killer and large granular lymphocytes cells were characterised by either immunohistochemical or phase contrast microscopical procedures on the initial biopsies from 15 children with coeliac disease. They were compared with seven individuals with partial villus atrophy and eight with normal villous morphology. Although the histological findings were similar in the initial biopsies of all patients with coeliac disease, the patients with permanent coeliac disease had a significantly lower number (0.41(0.61)cells/mm2) of large granular lymphocytes and natural killer cells compared with those patients with abortive coeliac disease (11.93 (6.23) cells/mm2). Those in the permanent group developed a significantly more pronounced flat mucosa after gluten challenge or provocation ...

NK cells have important functions in cancer immunosurveillance, bone marrow allograft rejection, fighting infections, tissue homeostasis and reproduction. NK cell-based therapies are promising treatments for blood cancers. Overcoming their currently limited efficacy requires a better understanding of the molecular mechanisms controlling NK cell development and dampening their effector functions. NK cells recognize the loss of self-antigens or upregulation of stress-induced ligands on pathogen-infected or tumor cells through invariant NK cell receptors (NKR), and then kill such stressed cells. Two second-messenger pathways downstream of NKRs are required for NK cell maturation and effector responses: PIP3-generation by PI3K, and generation of diacylglycerol and IP3 by PLCγ. Here, we identify a novel role for the phosphorylated IP3 metabolite inositol(1,3,4,5)tetrakisphosphate (IP4) in NK cells. IP4 promotes NK cell terminal differentiation and acquisition of a mature NKR repertoire. However, in ...

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Background: Human peripheral blood NK cells constitutively express CD56 and CD16 antigens. Peripheral blood NK cells seem to be strongly related with decidual NK cells, and may reflect the decidual NK cell functional status. There are varied reports concerning the relationship between NK cell cytotoxicity in women with recurrent spontaneous abortion. Objective: To study NK activity in women with history of RSA by using a non-radioactive cytotoxicity assay. Methods: Peripheral blood lymphocytes from RSA and healthy multiparous women were obtained. Lymphocytes were isolated and mixed with K562 NK-sensitive cell line. A non-radioactive method for NK cell cytotoxicity assessment was utilized. Dead K562 cell populations were detected by FACS Calibur flow cytometry, and the data obtained was analysed on cell-Quest software. The proportion of CD16+ /CD56+ cells was then calculated. Results: The proportion of NK cells were 9.21% ± 3.06 and 13.48% ± 4.09 in healthy women and RSA, respectively. The percentage

Human cytomegalovirus, a chief pathogen in immunocompromised people, can persist in a healthy immunocompetent host throughout life without being eliminated by the immune system. Here we show that pp65, the main tegument protein of human cytomegalovirus, inhibited natural killer cell cytotoxicity by an interaction with the activating receptor NKp30. This interaction was direct and specific, leading to dissociation of the linked CD3 from NKp30 and, consequently, to reduced killing. Thus, pp65 is a ligand for the NKp30 receptor and demonstrates a unique mechanism by which an intracellular viral protein causes general suppression of natural killer cell cytotoxicity by specific interaction with an activating receptor ...

Compared to GEA, AEA appears to preserve perioperative NKCC. This effect may be related to an attenuated stress hormone response associated with AEA. Cancer patients may have improved killing of embolized tumor cells during surgery performed under AEA.

treatment add-ons, you may be interested in some impartial and expert advice in two new scientific opinion papers published by the Royal College of Obstetricians and Gynaecologists (RCOG). They call for more high quality research into the role of natural killer cells in fertility and the effect of endometrial scratching on pregnancy outcomes.. Scientific Impact Papers (SIP), are up-to-date reviews of emerging or controversial scientific issues. The first paper looks at the role of uterine natural killer (uNK) cells, how they are measured, the role of testing and the evidence behind any links to improving implantation rates and early placental development. The paper clarifies that uNK cells are completely different from peripheral blood natural killer cells (which you would be testing in the blood tests some fertility clinics currently offer).. The paper makes it clear that there is no evidence to offer routine tests for NK cells as part of fertility treatment or testing, and that there is ...

TY - JOUR. T1 - An Ets element regulates the transcription of the human 2B4 gene in natural killer cells. AU - Vaidya, Swapnil V.. AU - Mathew, Porunelloor A.. PY - 2005/5/1. Y1 - 2005/5/1. N2 - 2B4 (CD244) acts as an activation receptor on human NK cells, whereas it sends inhibitory signals in murine NK cells. A previous study indicated a prominent role for AP-1 in the transcription of 2B4 gene. To further understand the transcriptional regulation we analyzed the upstream positive regulatory region (-1151 to -704) of the 2B4 promoter. We have identified an Ets element that regulates the 2B4 gene transcription in an AP1 dependent manner.. AB - 2B4 (CD244) acts as an activation receptor on human NK cells, whereas it sends inhibitory signals in murine NK cells. A previous study indicated a prominent role for AP-1 in the transcription of 2B4 gene. To further understand the transcriptional regulation we analyzed the upstream positive regulatory region (-1151 to -704) of the 2B4 promoter. We have ...

Natural killer (NK) cells are innate immune system lymphocytes with an integral role in host defense against HIV infection. and promote the cytotoxic features that Rabbit polyclonal to JAK1.Janus kinase 1 (JAK1), is a member of a new class of protein-tyrosine kinases (PTK) characterized by the presence of a second phosphotransferase-related domain immediately N-terminal to the PTK domain.The second phosphotransferase domain bears all the hallmarks of a protein kinase, although its structure differs significantly from that of the PTK and threonine/serine kinase family members. kill focus CBR 5884 on cells. Once older, NK cells circulate in the tissue and bloodstream even though surveying for contaminated or malignant cells. Although NK cells are formidable players in the immune system response against infections, genetically modifying NK cells expressing CARs could improve NK cell targeting of malignant and infected cells. Within this review, the function is certainly talked about by us of NK ...

Natural killer cell An innate effecter cells of immune system limits viremia and tumor burden Natural killer cell, also called NK cell, is a cell with large particles in the cytoplasm. NK cell is developed from bone marrow lymphoid stem cells, and its differentiation and development depend on bone marrow or thymus microenvironment, mainly distributed in peripheral blood and spleen, and a small amount in lymph nodes and other tissues. It is named because of its non-specific cytotoxicity. Without the receptors of T cells and B cells, there will be no genetic recombination of the recipient. But it still has some special receptors called "Killer cell immunoglobulin-like receptors (KIR)". KIR are a family of highly polymorphic activating and inhibitory receptors that serve as key regulators of NK cell function. NK cell is accounted about 5~10% of all lymphocytes, but NK cell can eliminate many kinds of pathogens and many kinds of tumor cells. NK cell contact with

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The T- and B-Lymphocyte and Natural Killer Cell Profile includes the following tests:. Percentage CD3+; absolute CD3+; percentage CD3+CD4+; absolute CD3+CD4+; percentage CD3+CD8+; absolute CD3+CD8+; percentage CD3-CD56+ natural killer (NK) cells; absolute CD3-CD56+ natural killer (NK) cells; percentage CD19+; absolute CD19+; CD4:CD8 ratio; CBC. .. HIV-1 infection results in a decrease of CD4 T cells, an increase in CD8 T cells, a decrease in the CD4:CD8 ratio, and a progressive destruction of immune function. Enumeration of CD4 and CD8 T cells in HIV-1 seropositive patients may be used for prognostic purposes and to monitor disease progression and retroviral therapy. Natural killer (NK) cells are large granular lymphocytes that mediate MHC-unrestricted cytotoxicity against virus-infected and malignant cells and manufacture a number of cytokines following stimulation of the immune system.. ...

A key mechanism of tumor resistance to immune cells is mediated by expression of peptide-loaded HLA class I molecule (HLA-E) in tumor cells, which suppresses NK cell activity via ligation of the NK inhibitory receptor CD94/NK group 2 member A (NKG2A). Gene expression data from approximately 10,000 tumor samples showed widespread HLAE expression, with levels correlating with those of KLRC1 (NKG2A) and KLRD1 (CD94). To bypass HLA-E inhibition, we developed a way to generate highly functional NK cells lacking NKG2A. Constructs containing a single-chain variable fragment derived from an anti-NKG2A antibody were linked to endoplasmic reticulum-retention domains. After retroviral transduction in human peripheral blood NK cells, these NKG2A protein expression blockers (PEBLs) abrogated NKG2A expression. The resulting NKG2Anull NK cells had higher cytotoxicity against HLA-E-expressing tumor cells. Transduction of anti-NKG2A PEBL produced more potent cytotoxicity than interference with an anti-NKG2A ...

The skin condition atopic dermatitis (AD) is driven by a type 2 immune response. Mack et al. performed high-dimensional immune profiling of patients with AD and revealed deficiencies in certain subsets of natural killer (NK) cells. NK cells showed signs of activation-induced cell death and were restored in patients that responded to immunotherapy. Circulating NK cells were also decreased in a mouse AD model; boosting NK cells with an IL-15 superagonist ameliorated symptoms in the mice. These results suggest that strategies to restore NK cells could help rebalance immunity in AD. ...

Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures.

TY - JOUR. T1 - Natural killer cells in cancer immunotherapy. AU - Miller, Jeffrey S.. AU - Lanier, Lewis L.. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Natural killer (NK) cells have evolved to complement T and B cells in host defense against pathogens and cancer. They recognize infected cells and tumors using a sophisticated array of activating, costimulatory, and inhibitory receptors that are expressed on NK cell subsets to create extensive functional diversity. NK cells can be targeted to kill with exquisite antigen specificity by antibody-dependent cellular cytotoxicity. NK and T cells share many of the costimulatory and inhibitory receptors that are currently under evaluation in the clinic for cancer immunotherapy. As with T cells, genetic engineering is being employed to modify NK cells to specifically target them to tumors and to enhance their effector functions. As the selective pressures exerted by immunotherapies to augment CD8+ T cell responses may result in loss of MHC class I, NK cells may ...

Consecutive serum samples were obtained from patients with syphilis before and on three occasions after treatment. The sera contained immunosuppresive factors associated with the immunoglobulin fraction, which could depress the natural killer cell activity of healthy controls. There was no evidence that allogeneic or lymphocytotoxic antibodies played a role in immuno-suppression, which could be reproduced with both soluble and insoluble antigen-IgG-antibody complexes.. ...

Natural killer (NK) cells are innate immune cells with the ability to recognize and eliminate virally infected cells and cancer cells without prior sensitization. There is a functional heterogeneity between individual NK cells, where some NK cells are more efficient at killing cancer cells than others. Methods that allow studies of single NK cells are required to understand the functional differences and how they correlate with the activation and development status of the NK cell.. This thesis focuses on the development and implementation of microchip- based imaging of NK cells, which is covered in five papers. Paper I presents a microchip screening platform for assessment of the cytotoxic potential of individual NK cells, by confining single NK cells together with target cells in microwells, followed by microscopy screening over extended time periods and automated image analysis. In paper II, the microchip platform was applied to test the ability of a novel trispecific killer engager (TriKE) to ...

Natural killer (NK) cells take up chylomicrons (CM), very low density (VLDL), low density (LDL), high density (HDL) and acetyl-modified low density (AcLDL) lipoproteins through different receptors, VLDL being the lipoprotein with the highest uptake and HDL the lowest. The uptake of LDL can be selectively blocked by the anti-LDL receptor, which does not affect the uptake of CM, VLDL, HDL and AcLDL. Although the uptake of lipoproteins assessed by flow cytometry using DiI is not very high, the lipoproteins are able to induce an increase in proliferative responses, VLDL, AcLDL and HDL being the most important ones with 12- and 17-fold increments, respectively. CM, VLDL and LDL at low concentrations increase NK cytotoxic activity, while HDL and AcLDL inhibit, in a dose-dependent fashion, the killing of NK cells against K562. These results suggest the presence of four different receptors that are responsible for the cytotoxic and proliferative responses observed ...

Definition of NATURAL KILLER CELL: NK cell. A lymphoid cell which kills a range of tumour cell targets in the absence of prior immunization and without evident antigen specificity. Morpholog

The anti-HIV activity of natural killer (NK) cells could be induced fast enough to potentially prevent the establishment of HIV infection. Epidemiological studies identified two genotypes encoding NK receptors that contribute to NK cell function, that were more frequent in people who remained uninfected despite multiple HIV exposures than in HIV-susceptible subjects. NK cells from carriers of the *h/*y+B*57 genotype have higher NK cell functional potential and inhibit HIV replication in autologous HIV-infected CD4+ T cells (iCD4) more potently than those from carriers of non-protective genotypes. HIV suppression depends on the secretion of CC-chemokines that block HIV entry into CD4+ cells. NK cell education and the effect of HIV infection on iCD4 cell surface expression of MHC-I antigens both influenced NK cell responses to autologous iCD4. The second KIR3DS1 homozygous protective genotype encodes an activating receptor that upon interacting with its HLA-F ligand on iCD4 induces anti-viral activity.

Human NK cells bear surface receptors that inhibit their cytolytic activity upon specific recognition of MHC class Ia Ags; little is known about the capacity of class Ib molecules to regulate NK cell function. We have studied the roles of different NK inhibitory receptors in recognition of the class Ib HLA-G. To this end, we analyzed the ability of an HLA-defective tumor cell line (721.221) transfected with the membrane form of HLA-G1, which contains the three external domains, to inhibit the cytolytic activity mediated by a panel of NK clones from several donors. A substantial proportion of peripheral blood NK clones appeared to be significantly inhibited by the HLA-G1-transfected cell line (referred to as .221-G1); nevertheless, no relation was observed between the expression and the function of serologically identifiable Ig-SF receptors (p58/p70) and specific recognition of .221-G1 cells. Moreover, p58 killer cell inhibitory receptor-IgG soluble fusion proteins specifically bound to 721.221 ...

TY - JOUR. T1 - Effect of Whole-Body Hyperthermia and Cyclophosphamide on Natural Killer Cell Activity in Murine Erythroleukemia. AU - Shen, Rong Nian. AU - Hornback, Ned B.. AU - Shidnia, Homayoon. AU - Lu, Li. AU - Broxmeyer, Hal E.. AU - Brahmi, Zacharie. PY - 1988/8/15. Y1 - 1988/8/15. N2 - Mice infected with the polycythemia-inducing strain of Friend virus complex (FVC-P) develop a fatal erythroid disease similar in some respects to leukemia. Six- to eight-week-old DBA/2 female mice were injected i.v. with 0.5 ml of a virus suspension containing approximately 5 x 104 plaque-forming units and 5 x 103 spleen focus-forming units. Four treatment regimens were begun 3 days postinjection: (a) no treatment; (b) whole-body hyperthermia (WBH) alone; (c) cyclophosphamide (CY) alone; (d) WBH combined with CY. WBH treatment utilized a microwave generator operating at 2450 MHz. The i.p. temperature of the mice receiving WBH was maintained at 39.5-40°C for 30 min. The CY was given i.p. at a dosage of 20 ...

Background: Although there is convincing data in support of the effectiveness of hyperthermia in tumor therapy, the molecular mechanisms underlying the clinical effects of hyperthermia are still poorly understood. Objective: To investigate natural killer (NK) cell cytotoxicity against heat-treated SW-872 and HeLa tumor cell lines. Methods: NKG2D ligands and HLA class I transcription were examined using quantitative real-time PCR in treated tumor cell lines at 0, 2, 4, 6 and 12 h following thermal treatment at 39C and 42C for 1 h. The expression of MICA/B, ULBP1 and ULBP2 were also determined by flow cytometry. NK92-MI cytotoxic activity against heat-treated target cell lines was assessed by LDH release as well as annexin-V and 7-AAD assays. Results: Our results showed that heat treatment at 39C improved the cytolytic activity of NK cells against SW-872 cells without increasing NKG2D ligand concentration or decreasing HLA class I levels. Conclusion: The observed increase in the cytotoxicity of

T-cell receptor gene rearrangement and expression in human natural killer cells: natural killer activity is not dependent on the rearrangement and expression of T-cell receptor alpha, beta, or gamma genes. Immunogenetics. 1988; 27(4):231-8 ...

Polymorphisms in cell surface receptors of natural killer cells and their ligands on target cells can affect susceptibility to viral infections including human immunodeficiency virus (HIV)-1. We found that the carriage of the human leukocyte antigen (HLA)-G minus 14-bp polymorphism, LILRB1 single nucleotide polymorphism rs1061680, and activating and inhibitory killer immunoglobulin-like receptors (KIRs) were different when data were compared between Caucasian, African Americans and Asian populations. However, carriage was similar when HIV-1 patients were compared with control donors, with the exception of the African American cohort.. ...

Emerging evidence suggests that NK cells could be important in the early effector response induced by vaccination, supported by vaccine antigen-specific CD4 IL-2 production and antigen-antibody immune complexes. Memory-like NK cells, with heightened responsiveness can be also generated by pre-activation with cytokines. I found that NK cell differentiation is accelerated in Africans in The Gambia compared to age-matched UK residents and that this is linked to reduced functional NK cell responses to cytokines. This effect may also relate to a high burden of human cytomegalovirus (HCMV) infection in this population, with all Gambian study subjects infected by 3 years of age. There is also significant variation in lymphoid and myeloid cell populations with increasing age. Additionally, I found that a deletion of the NKG2C gene, a receptor important for recognition of HCMV infected cells, results in delayed NK cell differentiation. Furthermore, the allele frequency of the NKG2C gene deletion is ...

Rabinowich H., Manciulea M., Metes D., Sulica A., Herberman R.B., Corey S.J., Whiteside T.L.. We recently reported that Fc mu R on NK cells is a signal transducing protein that stimulates a rapid increase in the level of cytoplasmic free calcium upon binding of IgM. This study was designed to examine signal transduction via the Fc mu R on NK cells and to characterize intracellular second messengers activated by IgM. Immunoprecipitation of IgM-bound Fc mu R by IgM-specific Ab coimmunoprecipitated the zeta- and Fc epsilon RI gamma-chains. Furthermore, engagement and clustering of Fc mu R by polyclonal IgM induced tyrosine phosphorylation of the zeta- and Fc epsilon RI gamma-chains, indicating their functional association with the Fc mu R-induced signal transduction cascade. Ligand-induced clustering of the Fc mu R also induced activity of src family kinases, Lck, Fyn, Lyn, and Src, as well as their physical interaction with the receptor. Triggering via Fc mu R also induced the activity of Syk and ...

TY - JOUR. T1 - Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells. AU - Sojka, Dorothy K.. AU - Plougastel-Douglas, Beatrice. AU - Yang, Liping. AU - Pak-Wittel, Melissa A.. AU - Artyomov, Maxim N.. AU - Ivanova, Yulia. AU - Zhong, Chao. AU - Chase, Julie M.. AU - Rothman, Paul B.. AU - Yu, Jenny. AU - Riley, Joan K.. AU - Zhu, Jinfang. AU - Tian, Zhigang. AU - Yokoyama, Wayne M.. PY - 2014/4/8. Y1 - 2014/4/8. N2 - Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a ...

Bridging innate and adaptive immunity, the NK cell is an important effector lymphocyte that participates in the early immune response to pathogens through the production of cytokines and chemokines (1). Furthermore, the NK cell has also been found to mediate cytolytic activity against virally infected cells and malignant cells (1, 2). Following the principle of the missing self hypothesis, NK recognition of self MHC Ags on putative target cells leads to inhibition of effector functions. Accordingly, target cell loss of self-MHC class I expression releases NK cell effector functions by removing the MHC-mediated inhibition (3). Regulation of NK cell function is accomplished through a diverse complement of receptors mediating, activating, and inhibiting signals in response to ligand interactions.. In humans, receptors that signal activation include the NK cytotoxicity receptors (4), whose ligands remain unclear, and NKG2D, which has been shown to recognize MHC class I chain-related proteins A ...

The researchers used an animal model to show that the loss of innate immune control by young natural killer cells can lead to infectious mononucleosis. Young natural killer cells, which small children in particular have in abundance, seem to be especially suited to killing off the cells that multiply EBV, according to Christian Münz, Professor of Experimental Immunology at the University of Zurich. This weakens the primary infection and infectious mononucleosis does not break out.. Without the defense of the natural killer cells, EBV multiplies so dramatically during the primary infection phase that the aggressive response of the adaptive immune system - chiefly of the T killer cells - makes the infected person sick with infectious mononucleosis. In the animal model we also observed weight loss and the increased occurrence of EBV-associated lymphomas. Consequently, natural killer cells seem to play a key role in the development of the primary infection with Epstein-Barr Virus. This is how ...

Horowitz, A., Strauss-Albee, D.M., Leipold, M. et al.. Natural killer (NK) cells play critical roles in immune defense and reproduction, yet remain the most poorly understood major lymphocyte population. Because their activation is controlled by a variety of combinatorially expressed activating and inhibitory receptors, NK cell diversity and function are closely linked. To provide an unprecedented understanding of NK cell repertoire diversity, we used mass cytometry to simultaneously analyze 37 parameters, including 28 NK cell receptors, on peripheral blood NK cells from 5 sets of monozygotic twins and 12 unrelated donors of defined human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genotype. This analysis revealed a remarkable degree of NK cell diversity, with an estimated 6000 to 30,000 phenotypic populations within an individual and >100,000 phenotypes in the donor panel. Genetics largely determined inhibitory receptor expression, whereas activation receptor ...

TY - JOUR. T1 - Tumor necrosis factor alpha (TNF-α) blockade improves natural killer cell (NK) activation, hypertension, and mitochondrial oxidative stress in a preclinical rat model of preeclampsia. AU - Cunningham, Mark W.. AU - Jayaram, Aswathi. AU - Deer, Evangeline. AU - Amaral, Lorena M.. AU - Vaka, Venkata Ramana. AU - Ibrahim, Tarek. AU - Cornelius, Denise C.. AU - LaMarca, Babbette. N1 - Funding Information: This study was supported by NIH grant RO1HD067541 (BL), NIH grants R00HL130456 and P20GM104357 (DCC), NIH P20GM121334 (BL, LMA), American heart association (AHA) early career award 19CDA34670055 (LMA), and the AHA early career grant award 18CDA34110264 (MWCJr). Publisher Copyright: © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.. PY - 2020. Y1 - 2020. N2 - The RUPP rat model of Preeclampsia exhibits hypertension (MAP), cytolytic natural killer (cNK) cells, tumor necrosis factor alpha (TNF-α) and mitochondrial Reactive Oxygen Species (mt ROS). Objective: ...

Gellert, Ginelle C. uPAR Interaction and Regulation of Natural Killer Cell Integrins: Implications for the Modulation of NK Cell Migration and Invasion. Doctor of Philosophy (Biomedical Sciences), May 2003; pp. 118, 2 tables; 12 figures; bibliography 163. The urokinase-type plasminogen activator receptor (uPAR) is a GPI-anchored receptor, devoid of an intracellular domain, but nevertheless initiates signaling, possibly through lateral interactions with integrins. Since adoptively transferred interleuking-2 (IL-2) activated natural killer (A-NK) cells can accumulate within established cancer metastases, these A-NK cells may integrate components of adhesion and proteolysis to facilitate their infiltration into tumors. The work in this dissertation investigates the hypothesis that uPAR directly interacts with and regulates the expression of integrins on the surface of NK cells in the potential modulation of NK cell migration and invasion. Crosslinking studies have revealed a relationship between the

In the present study, we provide evidence that freshly isolated neuroblastoma cells are susceptible to NK-mediated lysis. More importantly, we show that a key role in the lytic process is played by PVR, a molecule expressed at the tumor cell surface that is recognized by the DNAM-1 receptor. We analyzed highly purified, fresh neuroblastoma cells isolated from bone marrow aspirates (22) . As compared with cultured neuroblastoma cell lines (20) , freshly isolated neuroblasts were generally more resistant to lysis. Remarkably, a certain degree of variability existed among different tumors. In particular, we show that tumor cells displaying maximal susceptibility to lysis were characterized by high surface expression of PVR. This molecule was recently recognized as a ligand for DNAM-1, a surface receptor mediating NK cell activation and tumor cell killing (17) . In line with these findings, we now demonstrate that mAb-mediated disruption of DNAM-1-PVR interactions inhibits NK-mediated killing of ...

Natural killer (NK) cells play key roles in innate and adaptive immune responses against virus and tumor cells. Their function relies on the dynamic balance between activating and inhibiting signals through receptors that bind ligands expressed on target cells. The absence of inhibitory receptor engagement with their ligands and the presence of activating signals transmitted by activating receptors interacting with specific ligands, leads to NK cell activation (Lanier, 2005; Raulet et al., 2001). Thus, the balance of the ligands expressed for inhibitory and activating receptors determines whether NK cells will become activated to kill the target cells. This protocol allows to assign a precise ligand specificity to any given receptor on NK cells. Thus, if a tumor cell expresses the ligand, this protocol will allow to evaluate its interaction with the specific receptor. In particular, killer cell immunoglobulin (Ig)-like receptors (KIR) recognize their ligands (HLA class I molecules) through the direct

TY - JOUR. T1 - Use of natural killer cells as immunotherapy for leukaemia. AU - Grzywacz, Bartosz J. AU - Miller, Jeffrey S. AU - Verneris, Michael R. N1 - Funding Information: This work was funded by the Childrens Cancer Research Fund, Leukemia Research Fund, P01 CA111412 and P01 CA65493. Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2008/9. Y1 - 2008/9. N2 - Natural killer (NK) cells potentially play a significant role in eradicating residual disease following allogeneic haematopoietic cell transplantation, and have been explored as tools for adoptive immunotherapy for chemotherapy-refractory patients. NK cell cytotoxicity is modulated by multiple activating and inhibitory receptors that maintain a balance between self-tolerance and providing surveillance against pathogens and malignant transformation. The functional characteristics of NK cells are dictated by the strength of inhibitory receptor signalling. Major histocompatibility complex (MHC)-specific inhibitory ...

Author: Niemeyer, Marcus et al.; Genre: Journal Article; Published in Print: 2008-01; Keywords: transcriptomics; T helper cells; regulatory T cells; natural killer T cells; natural killer cells; Title: Natural killer T-cell characterization through gene expression profiling: an account of versatility bridging T helper type 1 (Th1), Th2 and Th17 immune responses

In cell biology, a lymphokine-activated killer cell (also known as a LAK cell) is a white blood cell that has been stimulated to kill tumor cells. If lymphocytes are cultured in the presence of Interleukin 2, it results in the development of effector cells which are cytotoxic to tumor cells. It has been shown that lymphocytes, when exposed to Interleukin 2, are capable of lysing fresh, non-cultured cancer cells, both primary and metastatic. LAK cells respond to these lymphokines, particularly IL-2, by lysing tumor cells that were already known to be resistant to NK cell activity. The mechanism of LAK cells is distinctive from that of natural killer cells because they can lyse cells that NK cells cannot. LAK cells are also capable of acting against cells that do not display the major histocompatibility complex, as has been shown by the ability to cause lysis in non-immunogenic, allogeneic and syngeneic tumors. LAK cells are specific to tumor cells and do not display activity against normal cells. ...

In this study, profoundly depressed NK cell activity was observed in a large subgroup of patients with sJRA and in only 1 of 20 patients with the polyarticular form of the disease. The extent of NK dysfunction in this group of patients was similar to that seen in patients with MAS [17] or HLH [12, 13]. The two study groups (sJRA versus other JRA subtypes) were well matched in terms of age, duration of the disease, and treatment regimens with the exception of a slightly higher proportion of patients with sJRA receiving steroids. Steroids have been reported to suppress the cytolytic activity of NK cells [22], and this might potentially have contributed to the observed differences in NK function. However, the logistic regression analysis did not show significant differences between groups defined on the basis of treatment regimens. In addition, several patients with sJRA who demonstrated profoundly depressed NK cell cytolytic activity were receiving only non-steroidal anti-inflammatory drugs. Owing ...

Natural killer (NK) cells play a key role in non-specific immune response in different cancers, including pancreatic cancer. However the anti-tumor effect of NK cells decreases during pancreatic cancer progression. The regulatory pathways by which NK cells facilitate tumor immune escape are unclear, therefore our purpose was to investigate the roles of the contributory factors. NK cells isolated from fresh healthy peripheral blood were co-cultured with normal human pancreatic ductal cells hTERT-HPNE and human pancreatic cancer cell lines SW1990 and BxPc-3 in vitro. Then NK cell function was determined by Flow cytometric analysis of surface receptors and cytotoxic granules in NK cells, NK cell apoptosis and cytotoxicity, and Enzyme-linked immunosorbent assay of cytokines. Expression level of MMP-9, IDO and COX-2 in hTERT-HPNE and SW1990 cells were detected by quantitative RT-PCR. Statistical differences between data groups were determined by independent t-tests using SPSS 19.0 software. Our results

Faculty of Engineering and Natural Sciences. SEMINAR. Natural Killer Cell Therapy in Multiple Myeloma: Towards a Phase I/II Clinical Trial. Tolga Sutlu, Karolinska Institute, Sweden. Abstract:. Despite the advances in autologous stem cell transplantation and chemotherapy, multiple myeloma (MM) remains an incurable disease. The most promising therapeutic options currently available are combinations of transplantation, targeted pharmacotherapy and immunotherapy. Cell-based immunotherapy after hematopoietic stem cell transplantation has been attempted but, with limited efficacy. Natural killer (NK) cells are interesting candidates for new means of immunotherapy; however, their potential clinical use in MM has not been extensively studied.. We have primarily attempted to determine if NK cells provide anti-MM activity following interleukin-2 (IL-2) administration, and if ex vivo activated and intravenously (i.v.) administered NK cells prolong survival in MM bearing C57BL/KaLwRij mice. IL-2 ...

Natural killer (NK) cells were first described 16 years ago. Studies with athymic or neonatally thymectomized mice showed they had relatively low incidences of carcinogen-induced tumors and good resistance during the initial encounter with viral infection. These mice lacked mature T cells, but had normal or elevated numbers of cells able to lyse certain tumor cell lines without prior stimulation. Subsequent studies have shown that NK activity can be enhanced by cytokines, specifically by interferons (IFN) and interleukin-2 (IL_2). A second type of unrestricted tumor cell killing has been described. Lymphocytes, incubated overnight with IL-2, acquire the ability to kill both fresh tumor cells and tumor cell lines resistant to killing by NK cells. These cells are known as lymphokine-activated (LAK) cells. This thesis will discuss the properties of LAK and NK cells, their unclear relationship with each other, and the regulatory effects of IFN and IL-2 on their activity.

Natural Killer (NK) cells contribute to the control of cancer through immunosurveillance and may influence phenotypic sculpting of cancer through immunoediting. NK cells may also contribute to the control of hematological malignancies such as acute myeloid leukemia (AML) following allogeneic stem cell transplantation. However, no studies have shown direct clinical evidence that supports immunoediting by NK cells in AML at presentation, or whether activating ligand expression at diagnosis serves as a prognostic indicator of survival. We now show that at diagnosis, expression of NK cell ligands on AML blast populations is heterogeneous. Furthermore, expression of multiple activating ligands is associated with favorable cytogenetics and improved leukemia-free survival. In analyses of paired diagnostic and relapse samples, AML blasts exhibiting lower expression of activating ligands were selectively increased at relapse, indicating that NK cell-mediated blast immunoediting occurred prior to AML ...

A first-in-human Phase I study of multiple myeloma patients combined expanded cord blood-derived natural killer cells with transplantation of a patients own stem cells and high-dose chemotherapy with little or none of the side effects seen with current treatments. Nina Shah, M.D. Multiple myeloma is a cancer that forms from white blood cells that are found in the bone marrow and are normally vital to a healthy immune system. Natural killer (NK) cells are white blood cells that roam through the blood stream, attacking infections and potentially cancer-causing cells. The technology to grow NK cells from umbilical cord blood was developed by Nina Shah, M.D., assistant professor and Elizabeth J. Shpall, M.D., professor in the department of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center. Results from the clinical study, led by Shah and Shpall, were presented today at the 57th Annual Meeting of the American Society of Hematology (ASH) annual ...

The permanent pancreas carcinoma cell line, PCI-24, was developed in order to analyse cytokine regulation on pancreas carcinoma and lymphokine-activated killer (LAK) cell interaction. PCI cells expressed ICAM-1 and HLA-ABC, but not HLA-DR antigens. PCI cells showed augmented ICAM-1 and HLA-ABC expression when incubated with interferon γ (IFNγ) and tumour necrosis factor α. A similar but weak augmentary effect on the HLA-ABC and ICAM-1 surface expression was seen with interleukin-1β treatment. Natural attachment of LAK to PCI cells was augmented by recombinant IFNγ in close association with ICAM-1 up-regulation on PCI cells. In addition, natural attachment was significantly inhibited by anti-LFA-1 and anti-ICAM-1 antibody treatments. Cytotoxicity of the LAK cells against PCI cells was also significantly inhibited with the same treatment. Thus, the attachment of LAK cells to PCI cells through LFA-1/ICAM-1 molecules appeared to be essential for the cytotoxicity for PCI cells. Pretreatment of PCI cells

In this study, we sought to address changes in blood lymphocyte subpopulations and labial salivary gland (LSG) inflammation after belimumab treatment in patients with primary Sjögrens syndrome (pSS) and to identify predictors of response to treatment. Sequential blood lymphocyte subsets and LSG biopsies were analysed between week 0 (W0) and W28 in 15 patients with pSS treated with belimumab. Systemic response to treatment was defined as a decrease in the European League Against Rheumatism Sjögrens Syndrome Disease Activity Index score of ≥3 points at W28. After belimumab, we observed a decrease in blood B lymphocytes primarily involving CD27-negative/immunoglobulin D-positive naïve B cells (p=0.008). Lymphocytic sialadenitis (focus score |1) that was present in 12 patients (80.0 %) before belimumab treatment became negative in 5 of them after treatment (p=0.03). The median (interquartile range) LSG B-cell/T-cell ratio decreased from 0.58 (0.5-0.67) to 0.50 (0.5-0.5) (p=0.06). B-cell activating

Severe asthma is typically characterized by chronic airway inflammation that is refractory to corticosteroids and associated with excess morbidity. Patients were recruited into the National Heart, Lung, and Blood Institute-sponsored Severe Asthma Research Program and comprehensively phenotyped by bronchoscopy. Bronchoalveolar lavage (BAL) cells were analyzed by flow cytometry. Compared with healthy individuals (n = 21), patients with asthma (n = 53) had fewer BAL natural killer (NK) cells. Patients with severe asthma (n = 29) had a marked increase in the ratios of CD4+ T cells to NK cells and neutrophils to NK cells. BAL NK cells in severe asthma were skewed toward the cytotoxic CD56dim subset, with significantly increased BAL fluid levels of the cytotoxic mediator granzyme A. The numbers of BAL CD56dim NK cells and CCR6−CCR4− T helper 1-enriched CD4+ T cells correlated inversely with lung function [forced expiratory volume in 1 s (FEV1) % predicted] in asthma. Relative to cells from healthy ...

The protein-bound polysaccharide PSK was tested for the ability to activate human natural killer (NK) cells. When blood lymphocytes and purified CD3-CD16 ?

The purpose of work described in this thesis was to (i) determine the contribution of innate immune responses to the early pro-inflammatory cytokine response to Plasmodium falciparum, (ii) describe the kinetics and cellular sources ofIFN-y production by human PBMC in response to activation by intact, infected erythrocytes (iRBC) or freeze-thawed schizont lysate (PfSL) and (iii) determine the activation requirements for innate immune cells responding to P. falciparum. Infected erythrocytes induce a more rapid and intense IFN-y response from malaria naive PBMC than does PfSL, correlating with rapid iRBC activation of CD3-CD56+ natural killer (NK) cells to produce IFN-y. There is marked heterogeneity between donors in the magnitude of the NK-IFN-y response not correlating with mitogen or cytokine-induced NK activation or prior malaria exposure. The NK-IFN-y response is highly IL-I2 dependent, partly IL-I8 dependent and highly dependent on direct contact between the NK cell and the parasitized ...

Alterations in natural killer (NK) cell number and function were examined in cigarette smokers and nonsmokers with silicosis, silica dust exposure without silicosis, or no exposure to rock dust. Blood NK cell number, percentage, and tumoricidal activity were measured in 120 hardrock miners, 57 of whom had radiographic evidence of silicosis, and in 33 community referents. There was a significant in

Cross-linking of FcγRIIIA (CD16) receptor on natural killer (NK) cells induces receptor-associated tyrosine kinase activation and tyrosine phosphorylation of numerous intracellular proteins, including phospholipase C (PLC)-γ1, PLC-γ2 and the associated ζ chain. Here we report that Vav, a proto-oncogene, also became tyrosine phosphorylated upon stimulation of CD16 in interleukin 2-activated NK cells (LAK-NK) as well as in an NK cell line, NK3.3. In addition, we observed that in LAK-NK cells, Vav was associated with a 70 kDa protein that also became tyrosine phosphorylated upon CD16 cross-linking. The association of this 70 kDa protein with Vav was disrupted by ionic detergent treatment. Tyrosine phosphorylation of Vav was inhibited by herbimycin A, a specific tyrosine kinase inhibitor. In vitro kinase assays with Vav immunoprecipitates derived from NK3.3 cells or LAK-NK cells resulted in the appearance of a phosphorylated 58 kDa protein, suggesting the presence of a kinase within the Vav ...

1. ReddehaseMJ. 2002 Antigens and immunoevasins: opponents in cytomegalovirus immune surveillance. Nat Rev Immunol 2 831 844. 2. LanierLL. 2008 Evolutionary struggles between NK cells and viruses. Nat Rev Immunol 8 259 268. 3. LodoenMB. LanierLL. 2006 Natural killer cells as an initial defense against pathogens. Curr Opin Immunol 18 391 398. 4. BironCA. ByronKS. SullivanJL. 1989 Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med 320 1731 1735. 5. JonjicS. BabicM. PolicB. KrmpoticA. 2008 Immune evasion of natural killer cells by viruses. Curr Opin Immunol 20 30 38. 6. PowersC. DeFilippisV. MalouliD. FruhK. 2008 Cytomegalovirus immune evasion. Curr Top Microbiol Immunol 325 333 359. 7. WilkinsonGW. TomasecP. StantonRJ. ArmstrongM. ProdhommeV. 2008 Modulation of natural killer cells by human cytomegalovirus. J Clin Virol 41 206 212. 8. LodoenMB. LanierLL. 2005 Viral modulation of NK cell immunity. Nat Rev Microbiol 3 59 69. 9. LjunggrenHG. KarreK. 1990 In ...

Therapeutic natural killer (NK) cell-mediated alloreactivity towards acute myeloid leukemia (AML) has largely been attributed to mismatches between killer immunoglobulin-like receptors (KIRs) on NK cells and their ligands, HLA class I molecules, on target cells. While adult acute B cell precursor leukemia (BCP-ALL) appears to be resistant to NK cell-mediated lysis, recent data indicate that pediatric BCP-ALL might yet be a target of NK cells. We here demonstrate in a donor-patient-specific NOD.Cg-Prkdc(scid) IL2rg(tmWjl)/Sz (NSG) xenotransplantation model that NK cells mediate considerable alloreactivity towards pediatric BCP-ALL in vivo. Notably, not only adoptively transferred mature, KIR(+) NK cells but also immature, KIR- NK cells arising early post transplantation in humanized NSG mice (huNSG) exerted substantial anti-leukemic activity. Low-dose and long-term treatment of huNSG mice with the DNA-demethylating agent 5-Aza-cytidine distinctly enhanced the anti-tumor response, interestingly ...

Researchers observed a marked increase in natural killer cells in HIV - positive children receiving massage therapy than those who did not receive massage. Natural killer cells are unique in that they attack only cells infected by a microbe. The children who did not receive massage had a steady decrease of these important immune cells, while those receiving treatment either remained stable or had an increase in natural killer cells ...

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The NK killing activity is regulated by activating and inhibitory NK receptors. All of the activating ligands identified so far are either viral or stress-induced proteins. The class I MHC proteins are the ligands for most of the inhibitory NK receptors. However, in the past few years, several receptors have been identified that are able to inhibit NK killing independently of class I MHC recognition. We have previously demonstrated the existence of a novel inhibitory mechanism of NK cell cytotoxicity mediated by the homophilic carcinoembryonic Ag (CEA)-related cell adhesion molecule 1 (CEACAM1) interactions. In this study, we demonstrate that CEACAM1 also interacts heterophilically with the CEA protein. Importantly, we show that these heterophilic interactions of CEA and CEACAM1 inhibit the killing by NK cells. Because CEA is expressed on a wide range of carcinomas and commonly used as tumor marker, these results represent a novel role for the CEA protein enabling the escape of tumor cells from NK

Background Hepatitis B virus (HBV) is accounting for over one million deaths annually due to immune-mediated chronic liver damage. Natural killer (NK) cells are abundant in the liver and contribute in HBV persistence. NK cytotoxic effects are controlled by signals from activating and inhibitory receptors. HBV may circumvent host antiviral immunity via the regulation of NK receptors and their ligands. We investigated the effect of viral replication and HBeAg mutations on NK mediators expression in the livers of chronic HBV (CHB) patients and in cell cultures.. Methods HBV monomers bearing hotspot mutations in the basal core promoter and precore region were transfected into HepG2 cells using a plasmid-free assay. Serum viremia and liver HBV RNA were measured in 19 CHB patients. The expression of HBV RNA and of NKG2D ligands, B7H6, DNAX accessory molecule-1, lectin-like transcript 1 (LLT1), LFA-1 and TRAIL was measured in the livers of CHB patients and transfected cells.. Results In general, high ...

Cell surface proteins major histocompatibility complex (MHC) class I-related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. Patches of cross-linked raft resident ganglioside GM1 colocalized with ULBP1, 2, 3, or MICA, but not CD45. Thus, ULBPs and MICA are expressed in lipid rafts at the cell surface. Western blotting revealed that glycosylphosphatidylinositol (GPI)-anchored ULBP3 but not transmembrane MICA, MHC class I protein, or transferrin receptor, accumulated in detergent-resistant membranes containing GM1. Thus, MICA may have a weaker association with lipid rafts than ULBP3, yet both proteins accumulate at an activating human NK cell immune synapse. Target cell lipid rafts marked by green fluorescent protein-tagged GPI also accumulate with ULBP3 at some synapses. Electron microscopy reveals constitutive clusters of ULBP at the cell surface. Regarding a specific molecular basis for

The antitumor activities of cytolytic T lymphocytes and natural killer cells are being increasingly investigated and exploited in cancer immunotherapy. One mechanism by which these cells recognize tumor cells is by engagement of NKG2D, an activating receptor on cytolytic T lymphocytes and natural killer cells, by MICA/B and ULBP family stress antigens.. In a study reported in Science Translational Medicine, Vantourout and colleagues showed that activation of EGFR is responsible for surface upregulation of NKG2D ligands in human epithelial cells in response to ultraviolet irradiation, osmotic shock, oxidative stress, and growth factor exposure. EGFR activation results in intracellular relocalization of adenylate-uridylate (AU)-rich element RNA-binding protein 1 (AUF1); AUF1 proteins normally destabilize NKG2D ligand mRNAs by targeting an AU-rich element that is conserved in the 3′ ends of most human, but not murine, NKG2D ligand genes. NKG2D ligand expression was positively correlated with EGFR ...

Immunodeficiency with natural killer cell deficiency (MCM4) Test Cost INR 30000.00 Surat Pune Jaipur Lucknow Kanpur Nagpur Visakhapatnam Indore Thane Bhopal Patna Vadodara Ghaziabad Ludhiana Coimbatore Madurai Meerut Ranchi Allahabad Trivandrum Pondicherry Mysore Aligarh best offer discount price

A first-in-human Phase I study of multiple myeloma patients combined expanded cord blood-derived natural killer cells with transplantation of a patients own stem cells and high-dose chemotherapy with little or none of the side effects seen with current treatments.. View article ...

Killer Cell Lectin Like Receptor D1 Human Recombinant, Killer Cell Lectin Like Receptor D1, Killer Cell Lectin-Like Receptor Subfamily D, Member 1, NK Cell Receptor, CD94 Antigen, CD94, KP43, Killer Cell Lectin-Like Receptor Subfamily D Member 1, Natural Killer Cells Antigen CD94, KLRD1.

Are natural killer cells the explanation for unexplained infertility, IVF failure, and repeated miscarriage? Learn what you need to know here.

Natural killer cells from aging mice treated with extracts from Echinacea purpurea are quantitatively and functionally rejuvenated.

Defects in NK and NKT cell activities have been implicated in the etiology of type 1 (autoimmune) diabetes in NOD mice on the basis of experiments performed using surrogate phenotypes for the identification of these lymphocyte subsets. Here, we have generated a congenic line of NOD mice (NOD.b-Nkrp1(b)) which express the allelic NK1.1 marker, enabling the direct study of NK and NKT cells in NOD mice. Major deficiencies in both populations were identified when NOD.b-Nkrp1(b) mice were compared with C57BL/6 and BALB.B6-Cmv1(r) mice by flow cytometry. The decrease in numbers of peripheral NK cells was associated with an increase in their numbers in the bone marrow, suggesting that a defect in NK cell export may be involved. In contrast, the most severe deficiency of NKT cells found was in the thymus, indicating that defects in thymic production were probably responsible. The deficiencies in NK cell activity in NOD mice could only partly be accounted for by the reduced numbers of NK cells, and fewer ...

INTRODUCTION. Human exposure to cadmium due to environmental factors is known to affect several tissues in the body.The major sources of exposure to cadmium are contaminated food and water, tobacco, and industrial fumes and dusts (Goyer & Cherian, 1995). Toxic effects of Cd have also been demonstrated on the bone formation and immune system (Nordberg, 1996) and (Waalkes et al., 1999). Cadmium causes damage both to humoral immune response and cell mediated immunity (Descotes, 1992; Dan et al., 2000). Cifone et al. (1989) demonstrated that the exposure to 200 and 400 ppm Cd of adult rats caused both inhibitory and stimulatory effects on natural killer cells activity and cytotoxic activity. Moreover, Hemdan et al. (2006) reported that Cd treatment exerted differential effects on cytokine production in human immunocompetent cells. Immunotoxic properties of most heavy metals is not well lit, and the underlying mechanisms are not fully understood. Therefore, the aim of this study, an important ...

article{9e6ef65e-280f-480c-95c2-8ec585bac8f7, abstract = {Secretory lysosomes of natural killer (NK) cells combine storage, regulated secretion and lysosomal activity. We asked whether one could target exogenous proteins to the secretory lysosomes of NK-cells for final delivery into a tumor site upon degranulation. cDNAs for both soluble and transmembrane (tm) proteins were expressed in the human YT-Indy NK-cell line. Targeting of a soluble TNF receptor (sTNFR1) was achieved by expressing a cDNA construct with a transmembrane sequence to facilitate ER-export and by incorporating a cytosolic sorting signal (Y) from CD63 to overcome constitutive secretion. The resulting sTNFR1-tm-Y was targeted to secretory lysosomes as confirmed by results from biosynthetic radiolabeling in combination with subcellular fractionation, immunoelectron microscopy, and immunofluorescence microscopy. A soluble sTNFR1 form was generated in the secretory lysosome by endogenous proteolytic activity. Expression of ...