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Natural Killer (natural + killer)
Kinds of Natural Killer Terms modified by Natural Killer Selected AbstractsRapid method for the analysis of peripheral chimerism in suspected graft-versus-host disease after liver transplantationLIVER TRANSPLANTATION, Issue 2 2000Amy B. Hahn The effects of microchimerism and possible tolerance have been well studied in orthotopic liver transplantation. In some patients, greater levels of donor cells persist in the periphery. These cells were characterized and their effects on clinical outcome were studied. Peripheral blood was obtained from patients at various times posttransplantation. HLA class II typing was performed by the polymerase chain reaction,sequence-specific primer method on unfractionated blood and lymphocyte subpopulations. Relative levels of amplification of donor and recipient alleles were compared. All patients studied had a low degree of chimerism that was most apparent in the CD8+T/natural killer (NK) cell population. One patient with persistently high levels of donor alleles in his CD8+T/NK cell population was diagnosed with severe graft-versus-host disease (GVHD) and died of opportunistic infections. Another patient with biopsy-proven GVHD was chimeric in several cell populations. On resolution of her symptoms, donor alleles were reduced to levels undetectable by this assay. These results suggest that persistently elevated levels of donor CD8+T/NK cells in the periphery may indicate GVHD in liver transplant recipients. This technique aids in rapid diagnosis, which facilitates appropriate treatment and thus may improve clinical outcome. [source] Defining the membrane proteome of NK cellsJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2010Dhimankrishna Ghosh Abstract The present study was initiated to define the composition of the membrane proteome of the Natural Killer (NK) like cell line YTS. Isolated membranes were treated with reagents that have been reported to remove peripheral membrane proteins. Additional steps involving trifluoroethanol (TFE) were introduced in an effort to remove remaining nonintegral membrane proteins. This treatment resulted in the release of a subset of proteins without any apparent disruption of membrane integrity. The membranes were solubilized and digested with trypsin in 25% TFE. The resulting peptides were separated using an off-line two-dimensional reversed phase LC technique at alkaline and acidic pHs. Mass spectrometric analysis identified 1843 proteins with high confidence scores. On the basis of the presence of transmembrane regions or evidence of posttranslational modifications and prediction algorithms, approximately 40% of the identified proteins were predicted as plausible membrane proteins. The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes. The analytical approaches presented in this study offer robust generic methods for the identification and characterization of membrane proteins. These observations highlight the fact that the membrane is a dynamic entity that is composed of integral and stably associated proteins. Copyright © 2009 John Wiley & Sons, Ltd. [source] ORIGINAL ARTICLE: Suppression of Natural Killer Cell Cytotoxicity in Postpartum WomenAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2010Maureen Groer Citation Groer M, El-Badri N, Djeu J, Harrington M, Van Eepoel J. Suppression of natural killer cell cytotoxicity in postpartum women. Am J Reprod Immunol 2010; 63: 209,213 Problem, Natural Killer (NK) cell numbers and cytotoxicity are suppressed during pregnancy. Little is known about postpartum NK number and function. Method of study, Postpartum women (n = 39) were studied at one week and then monthly over the first six postpartum months. The standard natural killer cell cytotoxicity assay (NKCA) was performed. This is a Cr51 release assay from K562 cells cultured with peripheral blood mononuclear cells (PBMCs). Results, Data indicate suppression of NK cytotoxicity in postpartum women. Cytotoxicity at each effector:target (E:T) ratio showed a drop from 1 week postpartum, reaching a nadir at around 2 months, and a trend towards recovery of cytotoxicity from 3 to 6 months. Lytic units (LUs) from pre-incubated cells from postpartum women were lower than age-matched, non-pregnant, non-postpartum controls through the fifth postpartum month. Conclusion, These data suggest that the postpartum period, like pregnancy, is characterized by decreased NK cytotoxicity activity. This suppressed NK cytotoxic effect may result as a response to interaction with tolerized fetal microchimeric cells accumulated during pregnancy in maternal blood and tissues. [source] ORIGINAL ARTICLE: Comparative Analysis of Peripheral Natural Killer Cells in the Two Phases of the Ovarian CycleAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Ageliki Pantazi Problem Changes in endometrial Natural Killer (NK) cells during the luteal phase of the ovarian cycle are important in initiating/maintaining a subsequent pregnancy. In the present study it was investigated whether during the menstrual cycle changes occur also in peripheral blood (PB) NKs. Method of study Blood samples during the follicular and the luteal phase were collected from 30 women without fertility problems. Samples were analyzed by flow-cytometry for: (1) NK cells (CD3,CD16+CD56+) and (2) intracellular production of interferon-, (IFN-,) by NK cells. For the comparison and correlation of the two populations between the two phases, Wilcoxon signed-rank test and Spearman's Coefficient were used. Results The differences in percentages of CD3,CD16+CD56+ cells and that of CD3,CD16+CD56+/IFN-,+ cells between the follicular and the luteal phase were not statistically significant (10.61 ± 5.11 versus 9.76 ± 4.57 and 6.48 ± 7.90 versus 7.30 ± 6.77, respectively, P > 0.05). The correlation between the two variables (NK% and NK/IFN-,%) was weakly positive (P = 0.07) only in the follicular phase. Conclusion The study did not reveal menstrual cycle-depended changes in PB NK cells. Thus, a suggestion to measure these cells in a specific phase of the cycle in order to predict the outcome of a subsequent pregnancy in women with fertility problems is objected. [source] REVIEW ARTICLE: Human NK Cells in Pregnant Uterus: Why There?AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2008Philippe Le Bouteiller Human Natural Killer (NK) cells are present in great number in pregnant uterine mucosa. They must be there for specialized functions, but which ones? This review discusses important recent observations that further contribute to this fascinating debate. Firstly, an array of corroborating findings indicates that uterine NK cell proliferation is synchronized with the cyclic surge of progesterone. Secondly, uterine NK cells are unlikely to exert a direct control on the embryo implantation. Thirdly, these NK cells influence the uterine vascular remodeling in early pregnancy but might not be the single key element that control trophoblast invasion. Finally, uterine NK cells are likely to be an important component of the local maternal immune response to pathogen infections. [source] Fas Antigen Expression on the Decidual Lymphocytes of Pre-Eclamptic PatientsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2000DOROTA DARMOCHWAL-KOLARZ PROBLEM: Apoptosis has been proposed as a mechanism for maintaining the homeostasis in the immune system. Activated lymphocytes are removed by a programmed cell death process Fas/FasL-mediated called activation induced cell death. The aim of the study was to investigate Fas antigen expression on decidual cells (T CD4+ lymphocytes, T CD8+ lymphocytes and Natural Killer (NK) cells) of pre-eclamptic patients and healthy pregnant women. METHOD OF STUDY: 12 pre-eclamptic patients and 10 healthy pregnant women were studied. Lymphocytes were isolated from decidual tissues mechanically, labeled by direct staining with monoclonal antibodies, and analyzed using the flow cytometric method. RESULTS: We found Fas antigen expression on decidual NK cells and T lymphocytes. CD 95 molecule expression and fluorescence intensity on NK cells of pre-eclamptic patients were lower when compared with controls (P<0.05). CONCLUSIONS: These findings suggest that decidual NK cells and T lymphocytes are able to undergo Fas/FasL-mediated apoptosis. It seems that NK cells' ability to undergo Fas/FasL-mediated apoptosis in pre-eclamptic patients can be altered because of lower CD95 molecule expression. [source] Potential Role of NKG2D and Its Ligands in Organ Transplantation: New Target for ImmunointerventionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2009B. Suárez-Álvarez NKG2D is one of the best characterized activating receptors on Natural Killer (NK) and CD8+ T cells. This receptor recognizes several different ligands (MICA/MICB and ULBPs) induced by cellular stress and infection. In addition to the role described in cancer surveillance, recent data highlight the importance of NKG2D and its ligands in organ transplantation. Allografts show evidence of MICA and MICB expression in both acute and chronic rejection. The presence of anti-MICA antibodies has been correlated with incidence of graft rejection. Furthermore, NKG2D-ligand engagement activates NK cells, which provides T-cell costimulation, and enhances antigen specific CTL-mediated cytotoxicity. Activated NK cells may function as a bridge between innate and adaptive immunity associated with transplantation. Activated NK cells in response to IL-15 can also trigger organ rejection through NKG2D and affect the maturation of both donor and recipient antigen presenting cells (APCs) and ultimately the T-cell allogeneic response. Regulatory T cells, which modulate T-cell responses in organ transplantation and infections, were reduced in numbers by NK cells exposed to intracellular pathogens, possibly via interaction with one NK2GD receptor. Blockage of NKG2D-NKG2D-L interactions provides a novel pathway for development of inhibitors. These studies have important clinical and therapeutic implications in solid organ transplantation. [source] Natural killer cells in viral hepatitis: facts and controversiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2010Mario U. Mondelli Eur J Clin Invest 2010; 40 (9): 851,863 Abstract Background, Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major human hepatotropic pathogens responsible for a large number of chronic infections worldwide. Their persistence is thought to result from inefficiencies of innate and adaptive immune responses; however, very little information is available on the former. Natural killer (NK) cells are a major component of innate immunity and their activity is tightly regulated by several inhibitory and activating receptors. Design, In this review, we examine controversial findings regarding the role of NK cells in the pathogenesis of acute and chronic liver disease caused by HCV and HBV. Results, Recent studies built up on technical advances to identify NK receptors and their functional correlates in this setting. While NK cells seem to behave correctly during acute hepatitis, it would appear that the NK cytotoxic potential is generally conserved in chronic hepatitis, if not increased in the case of HCV. In contrast, their ability to secrete antiviral cytokines such as interferon ex vivo or after cytokine stimulation is severely impaired. Conclusions, Current evidence suggests the existence of an NK cell functional dichotomy, which may contribute to virus persistence, while maintaining low-level chronic liver inflammation. The study of liver-infiltrating NK cells is still at the very beginning, but it is likely that it will shed more light on the role of this simple and at the same time complex innate immune cell in liver disease. [source] Manipulation of NK cytotoxicity by the IAP family member LivinEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2007Boaz Nachmias Abstract Natural killer (NK) cells are part of the innate immune system, capable of killing tumor and virally infected cells. NK cells induce apoptosis in the target cell by either granule- or receptor-mediated pathways. A set of inhibitory and activation ligands governs NK cell activation. As transformed cells often attempt to evade NK cell killing, up-regulation of a potential anti-apoptotic factor should provide a survival advantage. The inhibitor of apoptosis protein (IAP) family can inhibit apoptosis induced by a variety of stimuli. We have previously described a new IAP family member, termed Livin, which has two splice variants (, and ,) with differential anti-apoptotic activities. In this study, we explore the ability of Livin to inhibit NK cell-induced killing. We demonstrate that Livin,, moderately protects against NK cell killing whereas Livin,, augments killing. We show that Livin,, inhibition in Jurkat cells is apparent upon concomitant activation of an inhibitory signal, suggesting that Livin augments an extrinsic inhibitory signal rather than functioning as an independent inhibitory mechanism. Finally, we demonstrate that detection of both Livin isoforms in melanoma cells correlates with a low killing rate. To date, this is the first evidence that directly demonstrates the ability of IAP to protect against NK cell-induced apoptosis. [source] The KIR and CD94/NKG2 families of molecules in the rhesus monkeyIMMUNOLOGICAL REVIEWS, Issue 1 2001Michelle L. LaBonte Summary: Natural killer (NK) cells and a subset of T cells express families of receptors that are capable of detecting major histocompatibility complex (MHC) class I expression on the surface of cells. Molecules of the killer cell immunoglobulin-like receptor (KIR) family bind directly to MHC class I, while those of the CD94/NKG2 family recognize MHC class I signal sequences bound to HLA-E. Both the KIR and CD94/NKG2 families are composed of activating and inhibitory molecules that serve to regulate the function of NK cells as a result of their MHC class I recognition. Here we review the recently described KIR and CD94/NKG2 family members in the rhesus monkey. [source] Structural basis of MHC class I recognition by natural killer cell receptorsIMMUNOLOGICAL REVIEWS, Issue 1 2001Mark W. Sawicki Summary: Natural killer (NK)-cell function is regulated by NK receptors that recognize MHC class I (MHC-I) molecules on target cells. Two structurally distinct families of NK receptors have been identified, the immunoglobulin-like family (killer cell immunoglobulin-like receptors (KIRs), leukocyte immunoglobulin-like receptors (LIRs)) and the C-type lectin-like family (Ly49, CD94/NKG2A, NKG2D, CD69). Recently, the three-dimensional structures of several NK receptors were determined, in free form or bound to MHC-I. These include those of unbound KIRs, NKG2D, CD69, LIR-1 and the CD94 subunit of the CD94/NKG2A heterodimer. Together, these structures define the basic molecular architecture of both the immunoglobulin-like and C-type lectin-like families of NK receptors. In addition, crystal structures have been reported for the complex between Ly49A and H-2Dd, and for KIR2DL2 bound to HLA-Cw3. The complex structures provide a framework for understanding MHC-I recognition by NK receptors from both families and reveal striking differences in the nature of this recognition, despite the receptors' functional similarity. This research was supported, in part, by National Institutes of Health grants R01 AI47900 and R37 36900 (RAM) and a fellowship from the Cancer Research Institute (MWS). We are grateful to DW Wolan and IA Wilson for providing coordinates of NKG2D prior to publication, and to members of our laboratories for encouragement. [source] Natural killer cell cytotoxicity: how do they pull the trigger?IMMUNOLOGY, Issue 1 2009Nicola J. Topham Summary Natural killer (NK) cells target and kill aberrant cells, such as virally infected and tumorigenic cells. Killing is mediated by cytotoxic molecules which are stored within secretory lysosomes, a specialized exocytic organelle found in NK cells. Target cell recognition induces the formation of a lytic immunological synapse between the NK cell and its target. The polarized exocytosis of secretory lysosomes is then activated and these organelles release their cytotoxic contents at the lytic synapse, specifically killing the target cell. The essential role that secretory lysosome exocytosis plays in the cytotoxic function of NK cells is highlighted by immune disorders that are caused by the mutation of critical components of the exocytic machinery. This review will discuss recent studies on the molecular basis for NK cell secretory lysosome exocytosis and the immunological consequences of defects in the exocytic machinery. [source] Putting the natural killer cell in its placeIMMUNOLOGY, Issue 1 2006Geraldine M. O'Connor Summary Natural killer (NK) cells were originally described as ,null' lymphocytes, but we have increasing evidence of their role in recognizing pathogen, and our knowledge of NK cell receptors continues to expand exponentially. Human NK cells have many receptors for human leucoctye antigen (HLA) class I. These killer immunoglobulin-like receptors (KIRs) and CD94/NKG2 receptors can signal in both positive and negative ways to regulate NK cell functions. The inhibitory receptors are the best characterized, but even in these cases much of their functional biology remains elusive. In this review, some recent advances in terms of the three-immunoglobulin (3Ig)-domain KIRs are discussed. Natural cytotoxicity receptors (NCRs) are among the activatory receptors found on NK cells. While pathogen ligands for these receptors have been described, endogenous ligands remain elusive. NCRs and NKG2D, a receptor for stress-induced antigens, appear to play complementary functional roles in terms of NK cell activation. More recently described on NK cells are the Toll-like receptors. In particular, these receptors of the innate immune system allow NK cells to directly sense pathogen, and their ligation on accessory cells indirectly activates NK cells through cytokine production. It is becoming clear that none of these receptor systems functions in isolation and that it is the sum of the signals (which will reflect the pathogenic situation), in addition to the cytokine milieu, that will direct NK cell activation. The resulting cytotoxicity, cytokine production and direct cell,cell regulatory interactions with other cells of the immune system, for example dendritic cells, ultimately determine the role of the NK cell in the context of an overall immune response. [source] Host's innate immune response to fungal and bacterial agents in vitro: up-regulation of interleukin-15 gene expression resulting in enhanced natural killer cell activityIMMUNOLOGY, Issue 2 2003Phay Tran Summary Natural killer (NK) cells play an important role in the first line of defence against viral infections. We have shown earlier that exposure of human peripheral blood mononuclear cells (PBMC) to viruses results in rapid up-regulation of NK cell activity via interleukin-15 (IL-15) induction, and that this mechanism curtails viral infection in vitro. By using Candida albicans, Escherichia coli and Staphylococcus aureus, we now show here that exposure of PBMC to fungi and bacteria also results in an immediate increase of NK cytotoxicity. Reverse transcriptase,polymerase chain reaction and Western blot analyses as well as the use of antibodies against different cytokines revealed that IL-15 induction played a predominant role in this NK activation. These results indicate that IL-15 is also involved in the innate immune response against fungal and bacterial agents. [source] Natural killer cell-mediated ablation of metastatic liver tumors by hydrodynamic injection of IFN, gene to miceINTERNATIONAL JOURNAL OF CANCER, Issue 6 2007Tetsuo Takehara Abstract Interferon (IFN) , is a pleiotropic cytokine acting as an antiviral substance, cell growth inhibitor and immunomodulator. To evaluate the therapeutic efficacy and mechanisms of IFN, on hepatic metastasis of tumor cells, we hydrodynamically injected naked plasmid DNA encoding IFN,1 (pCMV-IFNa1) into Balb/cA mice having 2 days hepatic metastasis of CT-26 cells. Single injection of pCMV-IFNa1 efficiently enhanced the natural killer (NK) activity of hepatic mononuclear cells, induced production of IFN, in serum and led to complete rejection of tumors in the liver. Mice protected from hepatic metastasis by IFN, therapy displayed a tumor-specific cytotoxic T cell response and were resistant to subcutaneous challenge of CT-26 cells. NK cells were critically required for IFN,-mediated rejection of hepatic metastasis, because their depletion by injecting anti-asialo GM1 antibody completely abolished the antimetastatic effect. To find whether NK cells are directly activated by IFN, and are sufficient for the antimetastatic effect, the responses to IFN, were examined in SCID mice lacking T cells, B cells and NKT cells. IFN, completely rejected hepatic metastasis in SCID mice and efficiently activated SCID mononuclear cells, as evidenced by activation of STAT1 and a variety of genes, such as MHC class I, granzyme B, tumor necrosis factor-related apoptosis-inducing ligand and IFN,, and also enhanced Yac1 lytic ability. Study of IFN, knockout mice revealed that IFN, was not necessary for IFN,-mediated NK cell activation and metastasis protection. In conclusion, IFN, efficiently activates both innate and adaptive immune responses, but NK cells are critically required and sufficient for IFN,-mediated initial rejection of hepatic metastasis of microdisseminated tumors. © 2006 Wiley-Liss, Inc. [source] Compound KIR - HLA genotype analyses in the Iranian population by a novel PCR,SSP assayINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2010N. Tajik Summary Natural killer (NK) cells eliminate infected and transformed cells while still are self-tolerant. Interactions of the independently segregating Killer cell immunoglobulin-like receptors (KIR) and human leucocyte antigens (HLA) loci play a critical role in NK cell regulation. Different compound KIR-HLA genotypes can impart different thresholds of activation to the NK-cell repertoire and such genotypic variation has been found to confer altered risk in a number of human diseases including viral infections, autoimmune disorders, reproduction abnormalities and cancers. In this study, we presented a novel combined KIR-HLA polymerase chain reaction,sequence-specific primers genotyping assay for simultaneous determination of KIR genes and their three major HLA class I ligand groups (C1, C2, and Bw4). Moreover, known inhibitory and activating KIR + HLA (iKIR + HLA: 2DL2/3 + C1, 2DL1 + C2, 3DL1 + Bw4; and aKIR + HLA: 2DS2 + C1, 2DS1 + C2, 3DS1 + Bw4) combinations as well as co-inheritance of aKIR genes and iKIR + HLA pairs were analysed in a total of 200 unrelated healthy Iranian individuals. All tested subjects had at least one of the three iKIR + HLA pairs and the frequencies of various inhibitory combinations in the study group were: 31.5%, three iKIR + HLA pairs, 53.5%, two iKIR + HLA pairs, and 15%, 0ne iKIR + HLA pair. Furthermore, we revealed that majority of Iranians (69%) carry compound genotypes with greater number of inhibitory pairings than activating combinations (iKIR + HLA > aKIR + HLA). Conversely, iKIR + HLA < aKIR (45%) was dominant genotype in the study group. We conclude that selective evolutionary pressure has propensity to maintain KIR-HLA genotypes with more inhibitory combinations to guarantee self-tolerance. In contrast, existence of activating KIR genes without normal endogenous ligands, potentially arms the NK population for competent immunosurveillance and stronger defense against infections. [source] Improving methods of assessing natural killer cell cytotoxicityINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 1 2006Sandra E. Sephton Abstract Natural killer (NK) cells are a class of lymphocytes important in immune resistance to viral and other serious diseases. The cytotoxic function, or ,killing activity' of NK cells has become important in studies of the effects of stress and other psychosocial factors on physical health. Unfortunately, research on NK cell function has been plagued by discrepancies in the methods of interpreting NK cytotoxicity data. We briefly review some of the variations in measuring NK cell activity and present a new model for interpreting these results, introducing maximal target cell lysis (A) and the slope of the cytolytic curve (k) as parameters that attempt to make full use of the information and the statistical power in NK cell cytotoxicity data. Examples of these interpretation methods are presented using NK cytotoxicity data from a group of metastatic breast cancer patients. This approach will be useful in applications of NK cell measurement in psychoneuroimmunology research. Copyright © 2006 John Wiley & Sons, Ltd. [source] Bacillus Calmette-Guérin-pulsed dendritic cells stimulate natural killer T cells and ,,T cellsINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2007Michio Naoe Background: Immunotherapy with bacillus Calmette-Guérin (BCG) for bladder cancer is successful, although the precise mechanism is unclear. Natural killer (NK) cells are a candidate for BCG-activated killer cells, but the roles of other T lymphocytes, such as NKT cells and ,,T cells, are not fully understood. Mycobacterium tuberculosis is a potent activator of both NKT cells and ,,T cells. However, it is known that the patient's prognosis is good if there are increased numbers of dendritic cells (DCs) in the urine after BCG therapy. Therefore, we investigated whether DCs are matured by BCG and whether BCG-pulsed DCs stimulate NKT cells and ,,T cells. Methods: Naïve Pan T cells were isolated form peripheral blood mononuclear cells (PBMCs) and DCs were obtained by culturing CD14+ monocytes with granulocyte,macrophage colony-stimulating factor and interleukin-4. The DCs were pulsed with BCG and their maturation was measured by fluorescence-activated cell sorter analysis using the CD86 antibody. Naïve T lymphocytes were stimulated by coculture with BCG-pulsed DCs in vitro, followed by FACS analysis to estimate the ratio and activation of NKT cells and the ratio of ,,T cells. The 51Cr (chromium) release assay was used to estimate the cytotoxic activity of the stimulated T cells. Cytolytic proteins in the patient's PBMCs were measured during BCG therapy using semiquantitative reverse transcriptase-polymerase chain reaction. Results: The DCs were matured by BCG stimulation and the number of NKT cells and ,,T cells increased after culturing with BCG-pulsed DCs. The BCG-pulsed DCs also activated the NKT cells and ,,T cells. Also, the lymphocytes that were cocultured with the BCG-pulsed DCs showed unspecific cytotoxic activity against a bladder cancer cell line. Conclusion: Sensitization of NKT cells and ,,T cells by BCG-pulsed DCs might be one of the mechanisms of BCG immunotherapy. [source] ,-Endorphin Neuronal Cell Transplant Reduces Corticotropin Releasing Hormone Hyperresponse to Lipopolysaccharide and Eliminates Natural Killer Cell Functional Deficiencies in Fetal Alcohol Exposed RatsALCOHOLISM, Issue 5 2009Nadka I. Boyadjieva Background:, Natural killer (NK) cell dysfunction is associated with hyperresponse of corticotropin releasing hormone (CRH) to immune challenge and with a loss of ,-endorphin (BEP) neurons in fetal alcohol exposed animals. Recently, we established a method to differentiate neural stem cells into BEP neurons using cyclic adenosine monophosphate (cAMP)-elevating agents in cultures. Hence, we determined whether in vitro differentiated BEP neurons could be used for reversing the compromised stress response and immune function in fetal alcohol exposed rats. Methods:, To determine the effect of BEP neuron transplants on NK cell function, we implanted in vitro differentiated BEP neurons into the paraventricular nucleus of pubertal and adult male rats exposed to ethanol or control in utero. The functionality of transplanted BEP neurons was determined by measuring proopiomelanocortin (POMC) gene expression in these cells and their effects on CRH gene expression under basal and after lipopolysaccaride (LPS) challenge. In addition, the effectiveness of BEP neurons in activating NK cell functions is determined by measuring NK cell cytolytic activity and interferon-, (IFN-,) production in the spleen and in the peripheral blood mononuclear cell (PBMC) following cell transplantation. Results:, We showed here that when these in vitro differentiated BEP neurons were transplanted into the hypothalamus, they maintain biological functions by producing POMC and reducing the CRH neuronal response to the LPS challenge. BEP neuronal transplants significantly increased NK cell cytolytic activity in the spleen and in the PBMC and increased plasma levels of IFN-, in control and fetal alcohol exposed rats. Conclusions:, These data further establish the BEP neuronal regulatory role in the control of CRH and NK cell cytolytic function and identify a possible novel therapy to treat stress hyperresponse and immune deficiency in fetal alcohol exposed subjects. [source] Alcohol Suppresses IL-2,Induced CC Chemokine Production by Natural Killer CellsALCOHOLISM, Issue 9 2005Ting Zhang Background: Natural killer (NK) cells are a critical component of the host innate immune system. We investigated whether alcohol impairs NK cell function, particularly production of CC chemokines induced by interleukin (IL)-2, the natural ligands for CCR5 receptor. Methods: Primary NK cells and NK cell line (YTS) were cultured with or without alcohol (10 to 80 mM) for three hours. The culture supernatants were then harvested and used to treat human peripheral blood monocyte-derived macrophages and a HeLa cell line, which expresses CD4, CCR5, and CXCR4 receptors (MAGI cells). CC chemokine expression by YTS and primary NK cells treated with or without alcohol was analyzed with the real-time RT-PCR and ELISA. Ca2+i and Western blot assays were used to determine calcium-mediated intracellular signaling pathway and NF-,B p65 expression. HIV strains (Bal and UG024) were used to infect macrophages and MAGI cells. In addition, ADA (macrophage-tropic strain) and murine leukemia virus (MLV) envelope-pseudotyped HIV infection was carried out in macrophages. HIV infectivity was determined by HIV reverse transcriptase (RT) and ,-galactosidase activity assays. Results: Alcohol inhibited IL-2,induced CC chemokine (CCL3 and CCL4) expression by NK cells. Functional tests demonstrated that this reduced expression of CC chemokines was associated with diminished anti-HIV ability of NK cells. Alcohol also reduced the ability of NK cells to response to CCL3-mediated chemotaxis. Alcohol inhibited IL-2,induced NF-,B p65 protein expression and calcium mobilization by NK cells. Conclusions: Alcohol, through the inhibition of IL-2,induced NF-,B p65 protein expression and intracellular calcium mobilization, suppressed NK cell production of CC chemokines. This suppression of CC chemokine production was associated with diminished anti-HIV activity of NK cells. Thus, by inhibiting NK cell,mediated innate immunity against HIV, alcohol consumption may have a cofactor role in the immunopathogenesis of HIV disease. [source] Reduction of Perforin, Granzyme B, and Cytokine Interferon , by Ethanol in Male Fischer 344 RatsALCOHOLISM, Issue 4 2003Madhavi Dokur Background: Chronic alcohol consumption can impair the immune system and predispose individuals to an increased risk of cancer and infection. Natural killer (NK) cells are the first line of defense against viral, bacterial, and fungal infections and play an important role in cellular resistance to malignancy and tumor metastasis. We have shown previously that ethanol administration suppresses NK cell cytolytic activity in male Fischer rats. This study analyzed the effects of ethanol on perforin, granzyme B, and the cytokine interferon (IFN)-,, factors that modulate NK cell cytolytic activity, to understand the molecular mechanism involved in ethanol's suppression of NK cell activity. Methods: A group of male Fischer rats was fed an ethanol-containing diet (8.7% v/v), whereas a control group was pair-fed an isocaloric diet. At the end of 2 weeks, animals were decapitated, and spleen tissues were immediately removed and used for analysis of NK cell cytolytic activity, perforin, granzyme B, and IFN-, messenger RNA (mRNA) or protein levels. The mRNA levels of perforin, granzyme B, and IFN-, were evaluated by quantitative real-time polymerase chain reaction, and protein levels of these factors were analyzed by Western blot, enzyme-linked immunosorbent assay, or enzymatic activity assay. Results: Ethanol reduced the NK cell cytolytic activity and decreased the mRNA expression of perforin, granzyme B, and IFN-, in ethanol-fed animals when compared with pair-fed animals. Ethanol also significantly reduced the protein levels of perforin and IFN-, and the enzyme activity of granzyme B in alcohol-fed animals as compared with pair-fed animals. Conclusions: These data suggest that chronic ethanol consumption may suppress NK cell cytolytic activity in male Fischer rats by decreasing the production, activity, or both of granzyme B, perforin, and IFN-,. [source] Lipid solubility- and concentration-dependent attenuation of in vitro natural killer cell cytotoxicity by local anestheticsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2002J. Krog Background: Natural killer (NK) cells constitute an essential component of the innate immune system in the defence against infected and malignant cells. In this study the in vitro effect on NK cell activity of three different local anesthetics with different lipid solubility was investigated. Methods: Venous blood from seven healthy volunteers was incubated with three amide local anesthetics with three different concentrations of lipid solubility: lidocaine 0.50, 1.00 and 2.00 mg/ml, ropivacaine 0.375, 0.75 and 1.50 mg/ml, and bupivacaine 0.25, 0.50 and 1.00 mg/ml. After 1 h of incubation, mononuclear cells were isolated and cryopreserved until tested for NK cell cytotoxicity in a 4-h 51Cr-release assay against K-562 target cells. Natural killer cell cytotoxicity of mononuclear cells incubated with isotonic saline was used as the control. Results: A significant suppression in NK cell cytotoxicity was demonstrated for all three local anesthetic agents when the NK cell cytotoxicity was compared with the cytotoxicity estimated after incubation with the isotonic saline (P<0.004). Moreover a significant lipid solubility-dependent effect (P=0.0001) as well as an overall concentration-dependent effect (P<0.0001) on the NK cell cytotoxicity was found. Conclusion: The results of the present in vitro study suggest a negative association between the estimated NK cell cytotoxicity and the lipid solubility as well as the concentrations of the three local anesthetic agents tested. [source] Blood Lymphocyte Subpopulations, Neutrophil Phagocytosis and Proteinogram During Late Pregnancy and Postpartum in MaresREPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2008R Agrícola Contents The aim of this study was to evaluate peripheral blood lymphocyte subpopulations, neutrophil phagocytic capacity and proteinogram characteristics in mares, during the last trimester of pregnancy and in postpartum. Measurement of phagocytosis and quantification of T-lymphocyte subsets were done by flow cytometry. Quantification of T-lymphocyte subsets was performed with monoclonal antibodies specific for CD2, CD3, CD4 and CD8 cell markers. Natural killer and B-cell counts were estimated mathematically. Serum proteinogram was obtained by electrophoresis. No significant differences were observed between gestation and postpartum on CD4+, CD8+ and NK+ lymphocyte subsets, CD4 : CD8 ratio and phagocytosis. The percentage of cells expressing CD3 (64.2 ± 1.8) and CD2 (68.4 ± 1.7) (Mean ± SEM) was reduced during gestation vs postpartum (69.7 ± 1.5 and 73.8 ± 1.4 respectively) (p < 0.05). During pregnancy, CD19+ (31.6 ± 1.7) was higher than in postpartum (26.2 ± 1.4) (p < 0.05). Total T cells (2911 ± 227 cells/,l), T helper cells (2144 ± 169 cells/,l) and T-cytotoxic cells (767 ± 68 cells/,l) were depressed in pregnancy, when compared with postpartum (4093 ± 337 cells/,l; 3004 ± 276 cells/,l; 1089 ± 94 cells/,l respectively) (p < 0.01). Total white blood cell count was reduced during pregnancy (8815 ± 427 cells/,l) with respect to postpartum (10742 ± 446 cells/,l) (p < 0.01), while neutrophil count did not change. Total proteins, albumin, ,1,,2,,1, ,2, , globulins and albumin : globulin did not differ. Our results suggest that the physiological immune depression occurring in mares, during gestation might be due to T-helper and T-cytotoxic lymphocytes reduction. [source] REVIEW ARTICLE: The Unique Properties of Uterine NK CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Irit Manaster Citation Manaster I, Mandelboim O. The unique properties of uterine NK cells. Am J Reprod Immunol 2009 Abstract Natural killer (NK) cells are lymphocytes of the innate immunity system that are able to kill various hazardous pathogens and tumors. However, it is now widely accepted that NK cells also possess non-destructive functions, as has been demonstrated for uterine NK cells. Here, we review the unique properties of the NK cells in the uterine mucosa, prior to and during pregnancy. We discuss the phenotype and function of mouse and human endometrial and decidual NK cells and suggest that the major function of decidual NK cells is to assist in fetal development. We further discuss the origin of decidual NK cells and suggest several possibilities that might explain their accumulation in the decidua during pregnancy. [source] ORIGINAL ARTICLE: Activating Killer Cell Immunoglobulin-Like Receptor Genes' Association with Recurrent MiscarriageAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009Rafael Gustavo Vargas Problem, Natural killer (NK) cells are regulated through NK cell receptors such as killer cell immunoglobulin-like receptors (KIRs). KIRs are suspected of being involved in the causes of recurrent miscarriage (RM) as a higher proportion of activated NK cells were observed in women with RM when compared with that in controls. The aim of this study was to investigate if KIR genes coding for receptors known to have as ligands HLA class I molecules are correlated with RM. Method of study A matched case,control study was carried out in 68 south Brazilian Caucasian patient couples with RM and 68 control fertile couples. KIR genes were typed by PCR-Reverse SSO method. Results The rate of possession of an elevated number of activating KIR genes (positive for five or six activating KIR genes out of six different activating KIR genes analyzed) in RM patient women was significantly higher (P = 0.0201) when compared with that in control fertile women. These data suggest that women carrying a high content of activating KIR genes have about threefold increased probability to develop RM [OR = 2.71; 95% CI (1.23,6.01)]. Conclusion Our results indicate that RM could be associated with NK cell activation mediated by a profile rich in activating KIR genes. [source] Natural Killer Cells and the Immune Response in Solid Organ TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010W. Van Der Touw Natural killer (NK) cells have been characterized classically for their cytotoxicity against pathogen infected or stressed cells as well as for their role in monitoring the expression of self MHC I. However, the participation of NK cells in solid organ transplantation (SOT) is poorly defined due to conflicting clinical and animal model data. Preclinical models have shown that NK cells exacerbate T-cell allogeneic responses during rejection, but can also promote tolerance induction under immunosuppressive conditions. Further, while protocols such as costimulatory blockade effectively induce tolerance by blocking T-cell activation and promoting Treg generation, how such regimens regulate other innate and adaptive immune cells, including NK cells, is incomplete. This review examines NK cells and the regulation of their effector functions in SOT. [source] A 2·6 Mb interval on chromosome 6q25.2,q25.3 is commonly deleted in human nasal natural killer/T-cell lymphomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2003H. Sunny Sun Summary. Natural killer (NK)/T-cell lymphoma is a special subtype of rare malignant lymphoma that is more prevalent in Asia than in America and Europe. This newly characterized haemato-lymphoid malignancy is highly aggressive and frequently present in nasal and upper aerodigestive sites. Several studies have reported the commonly deleted region of chromosome 6q21,25 in this particular type of lymphoma. To refine the smallest region of overlapping (SRO) deletion for localization of potential tumour suppressor (TS) genes, we performed loss of heterozygosity (LOH) and homozygosity mapping of deletion (HOMOD) analyses on 37 nasal and nasal-type NK/T-cell lymphoma patients using a panel of 25 microsatellite markers, covering the 6q21,q25 region. In all patients studied, LOH was detected in eight (89%) paired-sample patients, while hemizygous deletion was detected in three (11%) single-sample patients. Combination of the LOH and HOMOD results defined a distinct 3 Mb SRO on chromosome 6q25. Quantitative multiplex polymerase chain reaction analysis of 10 sequence-tagged sites further refined the putative TS-gene-containing region to a 2·6 Mb interval between TIAM2 and SNX9. Eighteen known genes/Unigene clusters and 25 hypothetical genes are located within this 2·6 Mb region, but none are previously identified TS genes. These results provide a framework for future positional cloning of novel TS gene(s) at 6q25.2,q25.3. [source] Distribution of lymphoid neoplasms in the Republic of Korea: Analysis of 5318 cases according to the World Health Organization classification,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2010Sun Och Yoon Compared with the West, the overall incidence of lymphoid neoplasms is lower, and the subtype distribution is distinct in Asia. To comprehensively investigate the subtype distribution with the age and sex factors, and temporal changes of subtype proportions, we re-assessed all patients with lymphoid neoplasms diagnosed at a large oncology service in the Republic of Korea from 1989 to 2008 using the World Health Organization classifications. Of the total 5,318 patients, 66.9% had mature B-cell neoplasms, 12.5% had mature T/natural killer (NK)-cell neoplasms, 16.4% had precursor lymphoblastic leukemia/lymphoma (ALL/LBL), and 4.1% had Hodgkin's lymphoma. The most common subtypes were diffuse large B-cell lymphoma (30.5%), plasma cell myeloma (14.0%), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma; 12.4%), B-cell ALL/LBL (11.3%), Hodgkin's lymphoma (4.1%), peripheral T-cell lymphoma unspecified (4.0%), T-cell ALL/LBL (3.9%), and extranodal NK/T-cell lymphoma of nasal type (3.9%). Most subtypes showed male predominance, with an average M/F ratio of 1.3. Most mature lymphoid neoplasms were diseases of adults (mean age, 53.5 yr), whereas ALL/LBLs were of young individuals (mean age, 20.3 yr). When the relative proportion of subtypes were compared between two decades (1989,1998 vs. 1999,2008), especially MALT lymphoma has increased in proportion, whereas T/NK-cell neoplasms and ALL/LBL have slightly decreased. In summary, the lymphoid neoplasms of Koreans shared some epidemiologic features similar to those of other countries, whereas some subtypes showed distinct features. Although the increase in incidence of lymphoid neoplasms is relatively modest in Korea, recent increase of MALT lymphoma and decrease of T/NK-cell neoplasms and ALL/LBL are interesting findings. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Hepatocellular apoptosis associated with cytotoxic T/natural killer-cell infiltration in chronic active EBV infectionPATHOLOGY INTERNATIONAL, Issue 7 2009Yuko Nomura The aim of the present study was to identify the mechanism of hepatocellular apoptosis induced by EBV-infected cytotoxic T/natural killer (NK) cells in chronic active EBV infection (CAEBV). Eight patients with CAEBV were studied, and infected T-cell expansion and NK-cell expansion were detected in four patients each. Biopsy or necropsy was performed on lymph node, liver, or spleen, and each specimen was subjected to immunohistochemical double staining of CD3 plus caspase-3 with the addition of cytotoxic markers of T-cell restricted intracellular antigen-1 (TIA-1), perforin, and granzyme B, as well as EBV in situ hybridization (EBV-ISH). In the liver, some of the infiltrating CD3-positive lymphocytes stained positively for EBV-ISH and cytotoxic markers. Double staining of CD3 plus caspase-3 indicated caspase-3 positive hepatocytes with apoptotic features, accompanied by extensive infiltration of CD3-positive cells, which were directly attached to the apoptotic caspase-3 positive hepatocytes. In contrast, far fewer cells stained positive for caspase-3 in lymph node and spleen than in liver. The present findings suggest that in patients with CAEBV, cytotoxic T/NK cells may directly induce hepatocytes to undergo apoptosis more frequently than they do cells in other organs of the reticulo-endothelial system. [source] Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults: Overlap with chronic active EBV infection and infantile fulminant EBV T-LPDPATHOLOGY INTERNATIONAL, Issue 4 2008Koichi Ohshima EBV-associated T/natural killer (NK)-cell lymphoproliferative disorder (EBV-T/NK LPD) of children and young adults is generally referred to with the blanket nosological term of severe chronic active EBV infection (CAEBV). This disease is rare, associated with high morbidity and mortality, and appears to be more prevalent in East Asian countries. But because there is no grading or categorization system for CAEBV, pathologists and clinicians often disagree regarding diagnosis and therapy. EBV-T/NK LPD includes polyclonal, oligoclonal, and monoclonal proliferation of cytotoxic T and/or NK cells. Moreover, a unique disease previously described as infantile fulminant EBV-associated T-LPD has been identified and overlaps with EBV-T/NK LPD. In the present review a clinicopathological categorization of EBV-T/NK LPD is proposed, based on pathological evaluation and molecular data, as follows: (i) category A1, polymorphic LPD without clonal proliferation of EBV-infected cells; (ii) category A2, polymorphic LPD with clonality; (iii) category A3, monomorphic LPD (T-cell or NK cell lymphoma/leukemia) with clonality; and (iv) category B, monomorphic LPD (T-cell lymphoma) with clonality and fulminant course. Categories A1, A2, and A3 possibly constitute a continuous spectrum and together are equivalent to CAEBV. Category B is the exact equivalent of infantile fulminant EBV-associated T-LPD. It is expected that this categorization system will provide a guide for the better understanding of this disorder. This proposal was approved at the third meeting of the Asian Hematopathology Association (Nagoya, 2006). [source] | ||||||||||||||||||||||||||||||||||