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Sample records for cd1d-restricted nkt cells1

  1. Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells

    DEFF Research Database (Denmark)

    Blomqvist, Maria; Rhost, Sara; Teneberg, Susann;

    2009-01-01

    relevant isoforms C24:1 and C24:0, major constituents of the myelin sheet of the nervous system, and C16:0, prominent in the pancreatic islet beta-cells. The most potent sulfatide isoform was lysosulfatide (lacking a fatty acid). Shortened fatty acid chain length (C24:1 versus C18:1), or saturation...... isoforms by a CD1d-restricted NKT-cell clone, and suggest that sulfatide, a major component of the myelin sheet and pancreatic beta-cells, is one of several natural ligands for type II CD1d-restricted NKT cells....

  2. Bacterial CD1d-restricted glycolipids induce IL-10 production by human regulatory T cells upon cross-talk with invariant NKT cells.

    Science.gov (United States)

    Venken, Koen; Decruy, Tine; Aspeslagh, Sandrine; Van Calenbergh, Serge; Lambrecht, Bart N; Elewaut, Dirk

    2013-09-01

    Invariant NKT (iNKT) cells and CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) are important immune regulatory T cells with Ag reactivity to glycolipids and peptides, respectively. However, the functional interplay between these cells in humans is poorly understood. We show that Tregs suppress iNKT cell proliferation induced by CD1d-restricted glycolipids, including bacterial-derived diacylglycerols, as well as by innate-like activation. Inhibition was related to the potency of iNKT agonists, making diacylglycerol iNKT responses very prone to suppression. Cytokine production by iNKT cells was differentially modulated by Tregs because IL-4 production was reduced more profoundly compared with IFN-γ. A compelling observation was the significant production of IL-10 by Tregs after cell contact with iNKT cells, in particular in the presence of bacterial diacylglycerols. These iNKT-primed Tregs showed increased FOXP3 expression and superior suppressive function. Suppression of iNKT cell responses, but not conventional T cell responses, was IL-10 dependent, suggesting that there is a clear difference in mechanism between the Treg-mediated inhibition of these cell types. Our data highlight a physiologically relevant interaction between human iNKT and Tregs upon pathogen-derived glycolipid recognition that has a significant impact on the design of iNKT cell-based therapeutics.

  3. Bacillus anthracis lethal toxin disrupts TCR signaling in CD1d-restricted NKT cells leading to functional anergy.

    Directory of Open Access Journals (Sweden)

    Sunil K Joshi

    2009-09-01

    Full Text Available Exogenous CD1d-binding glycolipid (alpha-Galactosylceramide, alpha-GC stimulates TCR signaling and activation of type-1 natural killer-like T (NKT cells. Activated NKT cells play a central role in the regulation of adaptive and protective immune responses against pathogens and tumors. In the present study, we tested the effect of Bacillus anthracis lethal toxin (LT on NKT cells both in vivo and in vitro. LT is a binary toxin known to suppress host immune responses during anthrax disease and intoxicates cells by protective antigen (PA-mediated intracellular delivery of lethal factor (LF, a potent metalloprotease. We observed that NKT cells expressed anthrax toxin receptors (CMG-2 and TEM-8 and bound more PA than other immune cell types. A sub-lethal dose of LT administered in vivo in C57BL/6 mice decreased expression of the activation receptor NKG2D by NKT cells but not by NK cells. The in vivo administration of LT led to decreased TCR-induced cytokine secretion but did not affect TCR expression. Further analysis revealed LT-dependent inhibition of TCR-stimulated MAP kinase signaling in NKT cells attributable to LT cleavage of the MAP kinase kinase MEK-2. We propose that Bacillus anthracis-derived LT causes a novel form of functional anergy in NKT cells and therefore has potential for contributing to immune evasion by the pathogen.

  4. CD1d-restricted peripheral T cell lymphoma in mice and humans.

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    Bachy, Emmanuel; Urb, Mirjam; Chandra, Shilpi; Robinot, Rémy; Bricard, Gabriel; de Bernard, Simon; Traverse-Glehen, Alexandra; Gazzo, Sophie; Blond, Olivier; Khurana, Archana; Baseggio, Lucile; Heavican, Tayla; Ffrench, Martine; Crispatzu, Giuliano; Mondière, Paul; Schrader, Alexandra; Taillardet, Morgan; Thaunat, Olivier; Martin, Nadine; Dalle, Stéphane; Le Garff-Tavernier, Magali; Salles, Gilles; Lachuer, Joel; Hermine, Olivier; Asnafi, Vahid; Roussel, Mikael; Lamy, Thierry; Herling, Marco; Iqbal, Javeed; Buffat, Laurent; Marche, Patrice N; Gaulard, Philippe; Kronenberg, Mitchell; Defrance, Thierry; Genestier, Laurent

    2016-05-01

    Peripheral T cell lymphomas (PTCLs) are a heterogeneous entity of neoplasms with poor prognosis, lack of effective therapies, and a largely unknown pathophysiology. Identifying the mechanism of lymphomagenesis and cell-of-origin from which PTCLs arise is crucial for the development of efficient treatment strategies. In addition to the well-described thymic lymphomas, we found that p53-deficient mice also developed mature PTCLs that did not originate from conventional T cells but from CD1d-restricted NKT cells. PTCLs showed phenotypic features of activated NKT cells, such as PD-1 up-regulation and loss of NK1.1 expression. Injections of heat-killed Streptococcus pneumonia, known to express glycolipid antigens activating NKT cells, increased the incidence of these PTCLs, whereas Escherichia coli injection did not. Gene expression profile analyses indicated a significant down-regulation of genes in the TCR signaling pathway in PTCL, a common feature of chronically activated T cells. Targeting TCR signaling pathway in lymphoma cells, either with cyclosporine A or anti-CD1d blocking antibody, prolonged mice survival. Importantly, we identified human CD1d-restricted lymphoma cells within Vδ1 TCR-expressing PTCL. These results define a new subtype of PTCL and pave the way for the development of blocking anti-CD1d antibody for therapeutic purposes in humans. PMID:27069116

  5. CD4+ type II NKT cells mediate ICOS and programmed death-1-dependent regulation of type 1 diabetes

    DEFF Research Database (Denmark)

    Kadri, Nadir; Korpos, Eva; Gupta, Shashank;

    2012-01-01

    Type 1 diabetes (T1D) is a chronic autoimmune disease that results from T cell-mediated destruction of pancreatic ß cells. CD1d-restricted NKT lymphocytes have the ability to regulate immunity, including autoimmunity. We previously demonstrated that CD1d-restricted type II NKT cells, which carry...... diverse TCRs, prevented T1D in the NOD mouse model for the human disease. In this study, we show that CD4(+) 24aß type II NKT cells, but not CD4/CD8 double-negative NKT cells, were sufficient to downregulate diabetogenic CD4(+) BDC2.5 NOD T cells in adoptive transfer experiments. CD4(+) 24aß NKT cells...... in the pancreas draining lymph nodes. To our knowledge, these results provide for the first time cellular and molecular information on how type II CD1d-restricted NKT cells regulate T1D....

  6. Activation of CD1d-restricted natural killer T cells can inhibit cancer cell proliferation during chemotherapy by promoting the immune responses in murine mesothelioma.

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    Wu, Licun; Yun, Zhihong; Tagawa, Tetsuzo; De la Maza, Luis; Wu, Matthew Onn; Yu, Julie; Zhao, Yidan; de Perrot, Marc

    2014-12-01

    We studied the impact of natural killer T (NKT) cell activation by alpha-galactocysylceramide (α-GalCer, α-GC) on cancer cell repopulation during chemotherapy in murine mesothelioma. The number of NKT cells was found to be increased during the development of murine mesothelioma. NKT cells specifically recognize α-GC through CD1d resulting in their activation and expansion. Tumor-bearing mice were treated with chemotherapy once weekly, and α-GC was followed after each cycle of chemotherapy. Anti-tumor effect was evaluated on wild-type (WT) and CD1d knockout (CD1dKO) mice. Cancer cell proliferation and apoptosis were evaluated by Ki67 and TUNEL immunohistochemistry. CD4(+) and CD8(+) T cell proportion and activation in tumor, spleen, draining lymph node and peripheral blood were determined by flow cytometry, and gene expression of activated T cell-related cytokines was quantified by reverse transcription PCR. NKT cells were identified by CD1d-α-GC-tetramer staining. In WT mice, tumor growth delay was achieved by cisplatin (Cis), and this effect was improved in combination with α-GC, but α-GC alone had little effect. Cancer cell proliferation during chemotherapy was significantly inhibited by α-GC, while cancer cell death was significantly upregulated. α-GC following chemotherapy resulted in NKT cell expansion and an increase of interferon-γ production in the draining lymph node, blood and spleen. Gene expression of immune-associated cytokines was upregulated. Strikingly, the percentage of inducible T cell co-stimulator(+)CD4 T cells, Th17/Tc17 cells increased in splenocytes. In CD1d KO mice, however, Cis alone was less effective and Cis + α-GC provided no additional benefit over Cis alone. α-GC alone had minimal effect in both mice. NKT activation between cycles of chemotherapy could improve the outcome of mesothelioma treatment. PMID:25183171

  7. CD1d and invariant NKT cells at the human maternal–fetal interface

    OpenAIRE

    Boyson, Jonathan E.; Rybalov, Basya; Koopman, Louise A.; Exley, Mark; Balk, Steven P.; Racke, Frederick K.; Schatz, Frederick; Masch, Rachel; Wilson, S. Brian; Strominger, Jack L.

    2002-01-01

    Invariant CD1d-restricted natural killer T (iNKT) cells comprise a small, but significant, immunoregulatory T cell subset. Here, the presence of these cells and their CD1d ligand at the human maternal–fetal interface was investigated. Immunohistochemical staining of human decidua revealed the expression of CD1d on both villous and extravillous trophoblasts, the fetal cells that invade the maternal decidua. Decidual iNKT cells comprised 0.48% of the decidual CD3+ T cell population, a frequency...

  8. The adaptor protein SAP regulates type II NKT-cell development, cytokine production, and cytotoxicity against lymphoma.

    Science.gov (United States)

    Weng, Xiufang; Liao, Chia-Min; Bagchi, Sreya; Cardell, Susanna L; Stein, Paul L; Wang, Chyung-Ru

    2014-12-01

    CD1d-restricted NKT cells represent a unique lineage of immunoregulatory T cells that are divided into two groups, type I and type II, based on their TCR usage. Because there are no specific tools to identify type II NKT cells, little is known about their developmental requirements and functional regulation. In our previous study, we showed that signaling lymphocytic activation molecule associated protein (SAP) is essential for the development of type II NKT cells. Here, using a type II NKT-cell TCR transgenic mouse model, we demonstrated that CD1d-expressing hematopoietic cells, but not thymic epithelial cells, meditate efficient selection of type II NKT cells. Furthermore, we showed that SAP regulates type II NKT-cell development by controlling early growth response 2 protein and promyelocytic leukemia zinc finger expression. SAP-deficient 24αβ transgenic T cells (24αβ T cells) exhibited an immature phenotype with reduced Th2 cytokine-producing capacity and diminished cytotoxicity to CD1d-expressing lymphoma cells. The impaired IL-4 production by SAP-deficient 24αβ T cells was associated with reduced IFN regulatory factor 4 and GATA-3 induction following TCR stimulation. Collectively, these data suggest that SAP is critical for regulating type II NKT cell responses. Aberrant responses of these T cells may contribute to the immune dysregulation observed in X-linked lymphoproliferative disease caused by mutations in SAP.

  9. iNKT Cells and Their potential Lipid Ligands during Viral Infection

    Directory of Open Access Journals (Sweden)

    Anunya eOpasawatchai

    2015-07-01

    Full Text Available Invariant natural killer T (iNKT cells are a unique population of lipid reactive CD1d restricted innate-like T lymphocytes. Despite being a minor population, they serve as an early source of cytokines and promote immunological crosstalk thus bridging innate and adaptive immunity. Diseases ranging from allergy, autoimmunity, and cancer as well as infectious diseases, including viral infection, have been reported to be influenced by iNKT cells. However, it remains unclear how iNKT cells are activated during viral infection, as virus derived lipid antigens have not been reported. Cytokines may activate iNKT cells during infections from influenza and murine cytomegalovirus (MCMV, although CD1d dependent activation is evident in other viral infections. Several viruses, such as dengue virus (DENV, induce CD1d upregulation which correlates with iNKT cell activation. In contrast, Herpes simplex virus type 1 (HSV-1, Human immunodeficiency virus (HIV, Epstein-Barr virus (EBV and Human papiloma virus (HPV promote CD1d downregulation as a strategy to evade iNKT cell recognition. These observations suggest the participation of a CD1d-dependent process in the activation of iNKT cells in response to viral infection. Endogenous lipid ligands, including phospholipids as well as glycosphingolipids, such as glucosylceramide have been proposed to mediate iNKT cell activation. Pro-inflammatory signals produced during viral infection may stimulate iNKT cells through enhanced CD1d dependent endogenous lipid presentation. Furthermore, viral infection may alter lipid composition and inhibit endogenous lipid degradation. Recent advances in this field are reviewed.

  10. NKT cells mediate the recruitment of neutrophils by stimulating epithelial chemokine secretion during colitis.

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    Huang, Enyu; Liu, Ronghua; Lu, Zhou; Liu, Jiajing; Liu, Xiaoming; Zhang, Dan; Chu, Yiwei

    2016-05-27

    Ulcerative colitis (UC) is a kind of inflammatory bowel diseases characterized by chronic inflammation and ulcer in colon, and UC patients have increased risk of getting colorectal cancer. NKT cells are cells that express both NK cell markers and semi-invariant CD1d-restricted TCRs, can regulate immune responses via secreting a variety of cytokines upon activation. In our research, we found that the NKT cell-deficient CD1d(-/-) mice had relieved colitis in the DSS-induced colitis model. Further investigations revealed that the colon of CD1d(-/-) mice expressed less neutrophil-attracting chemokine CXCL 1, 2 and 3, and had decreased neutrophil infiltration. Infiltrated neutrophils also produced less reactive oxygen species (ROS) and TNF-α, indicating they may cause less epithelial damage. In addition, colitis-associated colorectal cancer was also relieved in CD1d(-/-) mice. During colitis, NKT cells strongly expressed TNF-α, which could stimulate CXCL 1, 2, 3 expressions by the epithelium. In conclusion, NKT cells can regulate colitis via the NKT cell-epithelium-neutrophil axis. Targeting this mechanism may help to improve the therapy of UC and prevent colitis-associated colorectal cancer. PMID:27063801

  11. Functional CD1d and/or NKT cell invariant chain transcript in horse, pig, African elephant and guinea pig, but not in ruminants

    OpenAIRE

    Looringh van Beeck, Frank A.; Reinink, Peter; Hermsen, Roel; Zajonc, Dirk M.; Laven, Marielle J.; Fun, Axel; Troskie, Milana; Schoemaker, Nico J.; Morar, Darshana; Lenstra, Johannes A.; Vervelde, Lonneke; Rutten, Victor P.M.G.; van Eden, Willem; Van Rhijn, Ildiko

    2009-01-01

    CD1d-restricted invariant natural killer T cells (NKT cells) have been well characterized in humans and mice, but it is unknown whether they are present in other species. Here we describe the invariant TCR α chain and the full length CD1d transcript of pig and horse. Molecular modeling predicts that porcine (po) invariant TCR α chain/poCD1d/α-GalCer and equine (eq) invariant TCR α chain/eqCD1d/α-GalCer form complexes that are highly homologous to the human complex. Since a prerequisite for th...

  12. Functional CD1d and/or NKT cell invariant chain transcript in horse, pig, African elephant and guinea pig, but not in ruminants

    OpenAIRE

    van Beeck, Frank A. Looringh; Reinink, Peter; Hermsen, Roel; Zajonc, Dirk M; Laven, Marielle J.; Fun, Axel; Troskie, Milana; Schoemaker, Nico J.; Morar, Darshana; Lenstra, Johannes A.; Vervelde, Lonneke; Victor P. M. G. Rutten; Van Eden, Willem; Van Rhijn, Ildiko

    2009-01-01

    CD1d-restricted invariant natural killer T cells (NKT cells) have been well characterized in humans and mice, but it is unknown whether they are present in other species. Here we describe the invariant TCR alpha chain and the full length CD1d transcript of pig and horse. Molecular modeling predicts that porcine (po) invariant TCR alpha chain/poCD1d/alpha-GalCer and equine (eq) invariant TCR alpha chain/eqCD1d/alpha-GalCer form complexes that are highly homologous to the human complex. Since a...

  13. Identification of a potent microbial lipid antigen for diverse Natural Killer T cells1

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    Wolf, Benjamin J.; Tatituri, Raju V. V.; Almeida, Catarina F.; Le Nours, Jérôme; Bhowruth, Veemal; Johnson, Darryl; Uldrich, Adam P.; Hsu, Fong-Fu; Brigl, Manfred; Besra, Gurdyal S.; Rossjohn, Jamie; Godfrey, Dale I.; Brenner, Michael B.

    2016-01-01

    Invariant Natural Killer T (iNKT) cells are a well-characterized CD1d-restricted T cell subset. The availability of potent antigens and tetramers for iNKT cells has allowed this population to be extensively studied and has revealed their central roles in infection, autoimmunity, and tumor immunity. In contrast, diverse Natural Killer T (dNKT) cells are poorly understood because the lipid antigens they recognize are largely unknown. We sought to identify dNKT cell lipid antigen(s) by interrogating a panel of dNKT mouse cell hybridomas with lipid extracts from the pathogen Listeria monocytogenes. We identified Listeria phosphatidylglycerol (PG) as a microbial antigen that was significantly more potent than a previously characterized dNKT cell antigen, mammalian PG. Further, while mammalian PG loaded CD1d tetramers did not stain dNKT cells, the Listeria-derived PG loaded tetramers did. The structure of Listeria PG was distinct from mammalian PG since it contained shorter, fully-saturated anteiso fatty acid lipid tails. CD1d binding lipid displacement studies revealed that the microbial PG antigen binds significantly better to CD1d than counterparts with the same headgroup. These data reveal a highly-potent microbial lipid antigen for a subset of dNKT cells and provide an explanation for its increased antigen potency compared to the mammalian counterpart. PMID:26254340

  14. Α-galactosylceramide analogs with weak agonist activity for human iNKT cells define new candidate anti-inflammatory agents.

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    Bricard, Gabriel; Venkataswamy, Manjunatha M; Yu, Karl O A; Im, Jin S; Ndonye, Rachel M; Howell, Amy R; Veerapen, Natacha; Illarionov, Petr A; Besra, Gurdyal S; Li, Qian; Chang, Young-Tae; Porcelli, Steven A

    2010-12-17

    CD1d-restricted natural killer T cells with invariant T cell receptor α chains (iNKT cells) are a unique lymphocyte subset that responds to recognition of specific lipid and glycolipid antigens. They are conserved between mice and humans and exert various immunoregulatory functions through their rapid secretion of a variety of cytokines and secondary activation of dendritic cells, B cells and NK cells. In the current study, we analyzed the range of functional activation states of human iNKT cells using a library of novel analogs of α-galactosylceramide (αGalCer), the prototypical iNKT cell antigen. Measurement of cytokines secreted by human iNKT cell clones over a wide range of glycolipid concentrations revealed that iNKT cell ligands could be classified into functional groups, correlating with weak versus strong agonistic activity. The findings established a hierarchy for induction of different cytokines, with thresholds for secretion being consistently lowest for IL-13, higher for interferon-γ (IFNγ), and even higher for IL-4. These findings suggested that human iNKT cells can be intrinsically polarized to selective production of IL-13 by maintaining a low level of activation using weak agonists, whereas selective polarization to IL-4 production cannot be achieved through modulating the strength of the activating ligand. In addition, using a newly designed in vitro system to assess the ability of human iNKT cells to transactivate NK cells, we found that robust secondary induction of interferon-γ secretion by NK cells was associated with strong but not weak agonist ligands of iNKT cells. These results indicate that polarization of human iNKT cell responses to Th2-like or anti-inflammatory effects may best be achieved through selective induction of IL-13 and suggest potential discrepancies with findings from mouse models that may be important in designing iNKT cell-based therapies in humans.

  15. Α-galactosylceramide analogs with weak agonist activity for human iNKT cells define new candidate anti-inflammatory agents.

    Directory of Open Access Journals (Sweden)

    Gabriel Bricard

    Full Text Available CD1d-restricted natural killer T cells with invariant T cell receptor α chains (iNKT cells are a unique lymphocyte subset that responds to recognition of specific lipid and glycolipid antigens. They are conserved between mice and humans and exert various immunoregulatory functions through their rapid secretion of a variety of cytokines and secondary activation of dendritic cells, B cells and NK cells. In the current study, we analyzed the range of functional activation states of human iNKT cells using a library of novel analogs of α-galactosylceramide (αGalCer, the prototypical iNKT cell antigen. Measurement of cytokines secreted by human iNKT cell clones over a wide range of glycolipid concentrations revealed that iNKT cell ligands could be classified into functional groups, correlating with weak versus strong agonistic activity. The findings established a hierarchy for induction of different cytokines, with thresholds for secretion being consistently lowest for IL-13, higher for interferon-γ (IFNγ, and even higher for IL-4. These findings suggested that human iNKT cells can be intrinsically polarized to selective production of IL-13 by maintaining a low level of activation using weak agonists, whereas selective polarization to IL-4 production cannot be achieved through modulating the strength of the activating ligand. In addition, using a newly designed in vitro system to assess the ability of human iNKT cells to transactivate NK cells, we found that robust secondary induction of interferon-γ secretion by NK cells was associated with strong but not weak agonist ligands of iNKT cells. These results indicate that polarization of human iNKT cell responses to Th2-like or anti-inflammatory effects may best be achieved through selective induction of IL-13 and suggest potential discrepancies with findings from mouse models that may be important in designing iNKT cell-based therapies in humans.

  16. Invariant NKT Cell Activation Induces Late Preterm Birth That Is Attenuated by Rosiglitazone.

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    St Louis, Derek; Romero, Roberto; Plazyo, Olesya; Arenas-Hernandez, Marcia; Panaitescu, Bogdan; Xu, Yi; Milovic, Tatjana; Xu, Zhonghui; Bhatti, Gaurav; Mi, Qing-Sheng; Drewlo, Sascha; Tarca, Adi L; Hassan, Sonia S; Gomez-Lopez, Nardhy

    2016-02-01

    Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality worldwide. Although intra-amniotic infection is a recognized cause of spontaneous preterm labor, the noninfection-related etiologies are poorly understood. In this article, we demonstrated that the expansion of activated CD1d-restricted invariant NKT (iNKT) cells in the third trimester by administration of α-galactosylceramide (α-GalCer) induced late PTB and neonatal mortality. In vivo imaging revealed that fetuses from mice that underwent α-GalCer-induced late PTB had bradycardia and died shortly after delivery. Yet, administration of α-GalCer in the second trimester did not cause pregnancy loss. Peroxisome proliferator-activated receptor (PPAR)γ activation, through rosiglitazone treatment, reduced the rate of α-GalCer-induced late PTB and improved neonatal survival. Administration of α-GalCer in the third trimester suppressed PPARγ activation, as shown by the downregulation of Fabp4 and Fatp4 in myometrial and decidual tissues, respectively; this suppression was rescued by rosiglitazone treatment. Administration of α-GalCer in the third trimester induced an increase in the activation of conventional CD4(+) T cells in myometrial tissues and the infiltration of activated macrophages, neutrophils, and mature dendritic cells to myometrial and/or decidual tissues. All of these effects were blunted after rosiglitazone treatment. Administration of α-GalCer also upregulated the expression of inflammatory genes at the maternal-fetal interface and systemically, and rosiglitazone treatment partially attenuated these responses. Finally, an increased infiltration of activated iNKT-like cells in human decidual tissues is associated with noninfection-related preterm labor/birth. Collectively, these results demonstrate that iNKT cell activation in vivo leads to late PTB by initiating innate and adaptive immune responses and suggest that the PPARγ pathway has potential as a target for

  17. CD1d-dependent expansion of NKT follicular helper cells in vivo and in vitro is a product of cellular proliferation and differentiation.

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    Rampuria, Pragya; Lang, Mark L

    2015-05-01

    NKT follicular helper cells (NKTfh cells) are a recently discovered functional subset of CD1d-restricted NKT cells. Given the potential for NKTfh cells to promote specific antibody responses and germinal center reactions, there is much interest in determining the conditions under which NKTfh cells proliferate and/or differentiate in vivo and in vitro. We confirm that NKTfh cells expressing the canonical semi-invariant Vα14 TCR were CXCR5(+)/ICOS(+)/PD-1(+)/Bcl6(+) and increased in number following administration of the CD1d-binding glycolipid α-galactosylceramide (α-GC) to C57Bl/6 mice. We show that the α-GC-stimulated increase in NKTfh cells was CD1d-dependent since the effect was diminished by reduced CD1d expression. In vivo and in vitro treatment with α-GC, singly or in combination with IL-2, showed that NKTfh cells increased in number to a greater extent than total NKT cells, but proliferation was near-identical in both populations. Acquisition of the NKTfh phenotype from an adoptively transferred PD-1-depleted cell population was also evident, showing that peripheral NKT cells differentiated into NKTfh cells. Therefore, the α-GC-stimulated, CD1d-dependent increase in peripheral NKTfh cells is a result of cellular proliferation and differentiation. These findings advance our understanding of the immune response following immunization with CD1d-binding glycolipids.

  18. α-Galactosylceramide-activated murine NK1.1(+) invariant-NKT cells in the myometrium induce miscarriages in mice.

    Science.gov (United States)

    Ichikawa, Tomoko; Negishi, Yasuyuki; Shimizu, Masumi; Takeshita, Toshiyuki; Takahashi, Hidemi

    2016-08-01

    Innate immunity, which is unable to discriminate self from allo-antigens, is thought to be important players in the induction of miscarriages. Here, we show that the administration of IL-12 to syngeneic-mated C57BL/6 mice on gestation day 7.5 (Gd 7.5), drives significant miscarriages in pregnant females. Furthermore, the administration on Gd 7.5 of α-galactosylceramide (α-GalCer), which is known to activate invariant natural killer T (iNKT) cells, induced miscarriages in both syngeneic-mated C57BL/6 mice and allogeneic-mated mice (C57BL/6 (♀) × BALB/c (♂)). Surprisingly, the percentages of both DEC-205(+) DCs and CD1d-restricted NK1.1(+) iNKT cells were higher in the myometrium of pregnant mice treated i.p. with α-GalCer than in the decidua. IL-12 secreted from α-GalCer-activated DEC-205(+) DCs stimulated the secretion of cytokines, including IL-2, IL-4, IFN-γ, TNF-α, perforin, and granzyme B, from the NK1.1(+) iNKT cells in the myometrium, leading to fetal loss in pregnant mice. Finally, the i.p. administration of IL-12 and/or α-GalCer in iNKT-deficient Jα18(-/-) (Jα18 KO) mice did not induce miscarriages. This study provides a new perspective on the importance of the myometrium, rather than the decidua, in regulating pregnancy and a mechanism of miscarriage mediated by activated DEC-205(+) DCs and NK1.1(+) iNKT cells in the myometrium of pregnant mice. PMID:27198610

  19. Cooperation of invariant NKT cells and CD46+CD256+ T regulatory cells in prevention of autoimmune diabetes in non-obese diabetic mice treated with α-galactosylceramide

    Institute of Scientific and Technical Information of China (English)

    Weipeng Li; Fang Ji; Yong Zhang; Ying Wang; Neng yang; Hailiang Ge; Fuqing Wang

    2008-01-01

    CD1d-restricted natural killer T (NKT) cells and CD4+CD25+regulatory T (Treg) cells are two thymus-derived subsets of regulatory T cells that play an important role in the maintenance of self-tolerance. Yet the functional changes of the two subsets of regulatory T cells in the development of diabetes in non-obese diabetic (NOD) mice remain unclear, and how NKT cells and CD4+CD25+ Treg cells cooperate functionally in the regulation of autoimmune diabetes is also uncertain.We provide evidence that in NOD mice, an animal model of human type 1 diabetes, the functions of both NKT cells and CD4+CD25+ Treg cells decrease in an age-dependent manner.We show that treatment with α-galactosylceramide increases the size of the CD4+CD25+ Treg cell compartment in NOD mice, and augments the expression of forkhead/winged helix transcription factor and the potency of CD4+CD25+ Treg cells to inhibit proliferation of CD4+CD25- T cells. Our data indicate that NKT cells and CD4+CD25+ Treg cells might cooperate in the prevention of autoimmune diabetes in NOD mice treated with α-galactosylceramide. Induced cooperation of NKT cells and CD4+CD25+ Treg cells could serve as a strategy to treat human autoimmune disease, such as type 1 diabetes.

  20. The function of iNKT cells in the exacerbation of bronchial asthma induced by fungi%iNKT细胞在真菌加重支气管哮喘中的作用

    Institute of Scientific and Technical Information of China (English)

    郑明睿; 刘海霞; 金先桥

    2014-01-01

    支气管哮喘(简称哮喘)是常见的慢性炎症性疾病,其发生发展受多种环境因素的影响.其中真菌可促进Th2炎症反应,是哮喘加重的重要危险因素,其加重哮喘的具体机制目前尚未明确.iNKT细胞已被证实在哮喘的发病机制中起重要作用,且最新研究发现,某些真菌的脂质抗原能够以CD1d分子限制性地激活iNKT细胞.因此,iNKT细胞作为免疫调节细胞,在真菌加重哮喘的免疫机制中是否起作用引起了人们的广泛关注和思考.本文主要针对iNKT细胞、真菌和哮喘三者之间的关系进行综述.%Bronchial asthma (asthma) is a common chronic inflammatory disease,and its occurrence or development is affected by many environmental factors.Fungi can promote the Th2 inflammatory and constitute an important risk factor of asthma exacerbations,but the exact mechanism of fungi induced asthma exacerbation is not yet clear,iNKT cells have been shown to play an important role in the pathogenesis of asthma.Besides,a latest research has found that certain fungal lipid antigens can activates invariant natural killer T cells in a CD1d restricted fashion.Therefore,whether iNKT cells,which act as immune regulatory cells,play an essential role in the fungi-induced asthma exacerbation has aroused great attention and deep thinking.In this paper,main emphasis is placed on the relationship between fungi,iNKT cells and asthma.

  1. NKT cells in HIV-1 infection

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Natural killer T (NKT) cells are a unique T cell population that have important immunoregulatory functions and have been shown to be involved in host immunity against a range of microorganisms. It also emerges that they might play a role in HIV-1 infection, and therefore be selectively depleted during the early stages of infection. Recent studies are reviewed regarding the dynamics of NKT depletion during HIV-I infection and their recovery under highly active antiretrovirai treatment (HAART). Possible mechanisms for these changes are proposed based on the recent developments in HIV pathogenesis. Further discussions are focused on HIV's disruption of NKT activation by downregulating CDId expression on antigen presentation cells (APC). HIV-1 protein Nefis found to play the major role by interrupting the intraceilular trafficking of nascent and recycling CDId molecules.

  2. NKT cell-TCR expression activates conventional T cells in vivo, but is largely dispensable for mature NKT cell biology.

    Directory of Open Access Journals (Sweden)

    J Christoph Vahl

    Full Text Available Natural killer T (NKT cell development depends on recognition of self-glycolipids via their semi-invariant Vα14i-TCR. However, to what extent TCR-mediated signals determine identity and function of mature NKT cells remains incompletely understood. To address this issue, we developed a mouse strain allowing conditional Vα14i-TCR expression from within the endogenous Tcrα locus. We demonstrate that naïve T cells are activated upon replacement of their endogenous TCR repertoire with Vα14i-restricted TCRs, but they do not differentiate into NKT cells. On the other hand, induced TCR ablation on mature NKT cells did not affect their lineage identity, homeostasis, or innate rapid cytokine secretion abilities. We therefore propose that peripheral NKT cells become unresponsive to and thus are independent of their autoreactive TCR.

  3. NK/T cell lymphoma associated with peripheral eosinophilia.

    Science.gov (United States)

    Yap, E; Wan Jamaluddin, W F; Tumian, N R; Mashuri, F; Mohammed, F; Tan, G C; Masir, N; Abdul Wahid, F S

    2014-12-01

    NK/T cell lymphoma, nasal type is an aggressive and uncommon malignancy. Disease that occurs outside of the aerodigestive tract exhibits an even more aggressive clinical behaviour and does not respond as well to conventional therapy compared to its nasal counterpart. We report such a case of NK/T cell lymphoma, nasal type, that presented as an anterior chest wall mass, arising from the left pectoralis muscle. An interesting feature we wish to highlight is the associated eosinophilia that corresponded to disease activity, exhibiting fluctuations with surgical resection and chemotherapy. To the best of our knowledge this is the third reported case of NK/T cell lymphoma that is associated with peripheral eosinophilia. Our case highlights the role of certain NK cell subsets that play a major role in eosinophilic activation in NK/T lymphomas and calls for more research into further classification of this disease by virtue of its NK cell subsets. PMID:25500520

  4. Immunologic glycosphingolipidomics and NKT cell development in mouse thymus

    DEFF Research Database (Denmark)

    Li, Yunsen; Thapa, Prakash; Hawke, David;

    2009-01-01

    Invariant NKT cells are a hybrid cell type of Natural Killer cells and T cells, whose development is dependent on thymic positive selection mediated by double positive thymocytes through their recognition of natural ligands presented by CD1d, a nonpolymorphic, non-MHC, MHC-like antigen presenting...... for identifying additional ligands for NKT cells. Our results also provide early insights into cellular lipidomics studies, with a specific focus on the important immunological functions of glycosphingolipids....

  5. B Cells Promote Th1- Skewed NKT Cell Response by CD1d-TCR Interaction

    OpenAIRE

    Shin, Jung Hoon; Park, Se-Ho

    2013-01-01

    CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although α-galactosylceramide (α-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-γ by NKT cells, concomitant with a d...

  6. From the Deep Sea to Everywhere: Environmental Antigens for iNKT Cells.

    Science.gov (United States)

    Wingender, Gerhard

    2016-08-01

    Invariant natural killer T (iNKT) cells are a unique subset of innate T cells that share features with innate NK cells and adaptive memory T cells. The first iNKT cell antigen described was found 1993 in a marine sponge and it took over 10 years for other, bacterial antigens to be described. Given the paucity of known bacterial iNKT cell antigens, it appeared as if iNKT cells play a very specialist role in the protection against few, rare and unusual pathogenic bacteria. However, in the last few years several publications painted a very different picture, suggesting that antigens for iNKT cells are found almost ubiquitous in the environment. These environmental iNKT cell antigens can shape the distribution, phenotype and function of iNKT cells. Here, these recent findings will be reviewed and their implications for the field will be outlined. PMID:26703211

  7. Chronic alcohol consumption enhances iNKT cell maturation and activation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hui, E-mail: hzhang@wsu.edu; Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G.

    2015-01-15

    Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1{sup −} iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1{sup +}CD44{sup hi} mature iNKT cells but does not alter the number of NK1.1{sup −} immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1{sup −} iNKT cells, especially the NK1.1{sup −}CD44{sup lo} Stage I iNKT cells. The percentage of NKG2A{sup +} iNKT cells increases in all of the tissues and organs examined; whereas CXCR3{sup +} iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. - Highlights: • Chronic alcohol consumption increases iNKT cells in the thymus and liver • Chronic alcohol consumption enhances thymic Stage I iNKT cell proliferation • Chronic alcohol consumption enhances iNKT cell maturation in thymus and periphery • Chronic alcohol

  8. NKT cells as an ideal anti-tumor immunotherapeutic

    Directory of Open Access Journals (Sweden)

    Shin-ichiro eFujii

    2013-12-01

    Full Text Available Human NKT cells are characterized by their expression of an invariant T cell antigen receptor (TCR  chain variable region encoded by a V24J18 rearrangement. These NKT cells recognize -galactosylceramide (-GalCer in conjunction with the MHC class-I-like CD1d molecule and bridge the innate and acquired immune systems to mediate efficient and augmented immune responses. A prime example of one such function is adjuvant activity: NKT cells augment anti-tumor responses because they can rapidly produce large amounts of IFN-, which acts on NK cells to eliminate MHC negative tumors and also on CD8 cytotoxic T cells to kill MHC positive tumors. Thus, upon administration of -GalCer-pulsed DCs, both MHC negative and positive tumor cells can be effectively eliminated, resulting in complete tumor eradication without tumor recurrence. Clinical trials have been completed in a cohort of 17 patients with advanced non-small cell lung cancers and 10 cases of head and neck tumors. Sixty percent of advanced lung cancer patients with high IFN- production had significantly prolonged median survival times (MST of 29.3 Mo with only the primary treatment. In the case of head and neck tumors, 10 patients who completed the trial all had stable disease or partial responses 5 wks after the combination therapy of -GalCer-DCs and activated NKT cells.We now focus on two potential powerful treatment options for the future. One is to establish artificial adjuvant vector cells containing tumor mRNA and -GalCer/CD1d. This stimulates host NKT cells followed by DC maturation and NK cell activation but also induces tumor-specific long-term memory CD8 killer T cell responses, suppressing tumor metastasis even one year after the initial single injection. The other approach is to establish induced pluripotent stem (iPS cells that can generate unlimited numbers of NKT cells with adjuvant activity. Such iPS-derived NKT cells produce IFN- in vitro and in vivo

  9. EBV-Induced Human CD8+ NKT Cells Synergize CD4+ NKT Cells Suppressing EBV-Associated Tumors upon Induction of Th1-Bias

    Institute of Scientific and Technical Information of China (English)

    Wei Xiao; Li Li; Rui Zhou; Ruijing Xiao; Yujuan Wang; Xiang Ji; Mengjun Wu; Lan Wang; Wei Huang; Xiaoling Zheng; Xinti Tan; Lang Chen; Tao Xiong; Jie Xiong; Youxin Jin; Jinquan Tan; Yuling He

    2009-01-01

    CD8+ natural killer T (NKT) cells from EBV-associated turnout patients are quantitatively and functionally impaired. EBV-induced CD8+ NKT cells drive syngeneic T cells into a Thl-bias response to suppress EBV-associated malignancies. IL-4-biased CD4+ NKT cells do not affect either syngeneic T cell cytotoxicity or Th cytokine secretion. Circulating mDC1 cells from patients with EBV-associated malignancies impair the production of IFN-γ by CD8+ NKT cells. In this study, we have established a human-thymus-SCID chimaera model to further investigate the underlying mechanism of EBV-induced CD8+ NKT cells in suppressing EBV-associated malignancies. In the human-thymus-SCID chimera, EBV-induced CD8+ NKT cells suppress EBV-associated malignancies in a manner dependent on the Th1-bias response and syngeneic CD3+ T cells. However, adoptive transfer with CD4+ NKT cells alone inhibits T cell immunity. Interestingly, CD4+ NKT cells themselves secrete high levels of IL-2, enhancing the persistence of adoptively transferred CD8+ NKT cells and T cells, thereby leading to a more pronounced T cell anti-tumour response in chimaeras co-transferred with CD4+ and CD8+ NKT cells. Thus, immune reconstitution with EBV-induced CD4+ and CD8+ NKT cells synergistically enhances T cell tumour immunity, providing a potential prophylactic and therapeutic treatment for EBV-associated malignancies. Cellular & Molecular Immunology. 2009;6(5):367-379.

  10. The adaptor molecule SAP plays essential roles during invariant NKT cell cytotoxicity and lytic synapse formation.

    Science.gov (United States)

    Das, Rupali; Bassiri, Hamid; Guan, Peng; Wiener, Susan; Banerjee, Pinaki P; Zhong, Ming-Chao; Veillette, André; Orange, Jordan S; Nichols, Kim E

    2013-04-25

    The adaptor molecule signaling lymphocytic activation molecule-associated protein (SAP) plays critical roles during invariant natural killer T (iNKT) cell ontogeny. As a result, SAP-deficient humans and mice lack iNKT cells. The strict developmental requirement for SAP has made it difficult to discern its possible involvement in mature iNKT cell functions. By using temporal Cre recombinase-mediated gene deletion to ablate SAP expression after completion of iNKT cell development, we demonstrate that SAP is essential for T-cell receptor (TCR)-induced iNKT cell cytotoxicity against T-cell and B-cell leukemia targets in vitro and iNKT-cell-mediated control of T-cell leukemia growth in vivo. These findings are not restricted to the murine system: silencing RNA-mediated suppression of SAP expression in human iNKT cells also significantly impairs TCR-induced cytolysis. Mechanistic studies reveal that iNKT cell killing requires the tyrosine kinase Fyn, a known SAP-binding protein. Furthermore, SAP expression is required within iNKT cells to facilitate their interaction with T-cell targets and induce reorientation of the microtubule-organizing center to the immunologic synapse (IS). Collectively, these studies highlight a novel and essential role for SAP during iNKT cell cytotoxicity and formation of a functional IS.

  11. Role of NK, NKT cells and macrophages in liver transplantation

    Science.gov (United States)

    Fahrner, René; Dondorf, Felix; Ardelt, Michael; Settmacher, Utz; Rauchfuss, Falk

    2016-01-01

    Liver transplantation has become the treatment of choice for acute or chronic liver disease. Because the liver acts as an innate immunity-dominant organ, there are immunological differences between the liver and other organs. The specific features of hepatic natural killer (NK), NKT and Kupffer cells and their role in the mechanism of liver transplant rejection, tolerance and hepatic ischemia-reperfusion injury are discussed in this review. PMID:27468206

  12. Border Patrol Gone Awry: Lung NKT Cell Activation by Francisella tularensis Exacerbates Tularemia-Like Disease.

    Science.gov (United States)

    Hill, Timothy M; Gilchuk, Pavlo; Cicek, Basak B; Osina, Maria A; Boyd, Kelli L; Durrant, Douglas M; Metzger, Dennis W; Khanna, Kamal M; Joyce, Sebastian

    2015-06-01

    The respiratory mucosa is a major site for pathogen invasion and, hence, a site requiring constant immune surveillance. The type I, semi-invariant natural killer T (NKT) cells are enriched within the lung vasculature. Despite optimal positioning, the role of NKT cells in respiratory infectious diseases remains poorly understood. Hence, we assessed their function in a murine model of pulmonary tularemia--because tularemia is a sepsis-like proinflammatory disease and NKT cells are known to control the cellular and humoral responses underlying sepsis. Here we show for the first time that respiratory infection with Francisella tularensis live vaccine strain resulted in rapid accumulation of NKT cells within the lung interstitium. Activated NKT cells produced interferon-γ and promoted both local and systemic proinflammatory responses. Consistent with these results, NKT cell-deficient mice showed reduced inflammatory cytokine and chemokine response yet they survived the infection better than their wild type counterparts. Strikingly, NKT cell-deficient mice had increased lymphocytic infiltration in the lungs that organized into tertiary lymphoid structures resembling induced bronchus-associated lymphoid tissue (iBALT) at the peak of infection. Thus, NKT cell activation by F. tularensis infection hampers iBALT formation and promotes a systemic proinflammatory response, which exacerbates severe pulmonary tularemia-like disease in mice.

  13. Effects of Invariant NKT Cells on Parasite Infections and Hygiene Hypothesis

    Directory of Open Access Journals (Sweden)

    Jun-Qi Yang

    2016-01-01

    Full Text Available Invariant natural killer T (iNKT cells are unique subset of innate-like T cells recognizing glycolipids. iNKT cells can rapidly produce copious amounts of cytokines upon antigen stimulation and exert potent immunomodulatory activities for a wide variety of immune responses and diseases. We have revealed the regulatory effect of iNKT cells on autoimmunity with a serial of publications. On the other hand, the role of iNKT cells in parasitic infections, especially in recently attractive topic “hygiene hypothesis,” has not been clearly defined yet. Bacterial and parasitic cell wall is a cellular structure highly enriched in a variety of glycolipids and lipoproteins, some of which may serve as natural ligands of iNKT cells. In this review, we mainly summarized the recent findings on the roles and underlying mechanisms of iNKT cells in parasite infections and their cross-talk with Th1, Th2, Th17, Treg, and innate lymphoid cells. In most cases, iNKT cells exert regulatory or direct cytotoxic roles to protect hosts against parasite infections. We put particular emphasis as well on the identification of the natural ligands from parasites and the involvement of iNKT cells in the hygiene hypothesis.

  14. Roles of CID1d-Restricted NKT cells in the intestine

    NARCIS (Netherlands)

    van Dieren, Jolanda M.; van der Woude, C. Janneke; Kuipers, Ernst J.; Escher, Johanna C.; Samsom, Janneke N.; Blumberg, Richard S.; Nieuwenhuis, Edward E. S.

    2007-01-01

    Natural killer T (NKT) cells are a subset of lymphocytes that express cell surface molecules of both conventional T cells and natural killer cells and share the features of both innate and adaptive immune cells. NKT cells have been proposed to make both protective and pathogenic contributions to inf

  15. Retinoic acid alleviates Con A-induced hepatitis and differentially regulates effector production in NKT cells.

    Science.gov (United States)

    Lee, Kyoo-A; Song, You Chan; Kim, Ga-Young; Choi, Gyeyoung; Lee, Yoon-Sook; Lee, Jung-Mi; Kang, Chang-Yuil

    2012-07-01

    Retinoic acid (RA) is a diverse regulator of immune responses. Although RA promotes natural killer T (NKT) cell activation in vitro by increasing CD1d expression on antigen-presenting cells (APCs), the direct effects of RA on NKT-cell responses in vivo are not known. In the present study, we demonstrated the effect of RA on the severity of Con A-induced hepatitis and molecular changes of NKT cells. First, we demonstrated that Con A-induced liver damage was ameliorated by RA. In correlation with cytokine levels in serum, RA regulated the production of IFN-γ and IL-4 but not TNF-α by NKT cells without influencing the NKT-cell activation status. However, RA did not alleviate α-GalCer-induced liver injury, even though it reduced IFN-γ and IL-4 but not TNF-α levels in serum. This regulation was also detected when liver mononuclear cells (MNCs) or NKT hybridoma cells were treated with RA in vitro. The regulatory effect of RA on NKT cells was mediated by RAR-α, and RA reduced the phosphorylation of MAPK. These results suggest that RA differentially modulates the production of effector cytokines by NKT cells in hepatitis, and the suppressive effect of RA on hepatitis varies with the pathogenic mechanism of liver injury.

  16. EBV-induced human CD8+ NKT cells synergize CD4+NKT cells suppressing EBV-associated tumors upon induction of Th1 bias

    Institute of Scientific and Technical Information of China (English)

    Wei Xiao; Xiaoling Zheng; Xinti Tan; Lang Chen; Tao Xiong; Jie Xiong; Youxin Jin; Jinquan Tan; Yuling He; Li Li; Rui Zhou; Ruijing Xiao; Yujuan Wang; Xiang Ji; Mengjun Wu; Lan Wang; Wei Huang

    2011-01-01

    @@ The authors inadvertently published histograms in the fourth panel to the right in both rows of Figure 4c that were actually the data of CD8+NKT cells from EBV-exposed CD8+ NKT cell-transferred, or EBV-exposed CD4 + and CD8 + NKT-transferred hu-thym-SCID chimeras.The corrected figure included here contains the histograms that correctly represent the data of T ceils from EBV-exposed CD4+ and CD8+NKT-transferred hu-thym-SCID chimeras.Since the fourth panels to the right in both rows of Figure 4c show the cellular proliferation using the CFSE labeling technique, the histogram substitutions do not alter the conclusions that were drawn from the original data.The authors would like to apologize for their mistake.

  17. Paucity of CD4+ natural killer T (NKT lymphocytes in sooty mangabeys is associated with lack of NKT cell depletion after SIV infection.

    Directory of Open Access Journals (Sweden)

    Namita Rout

    Full Text Available Lack of chronic immune activation in the presence of persistent viremia is a key feature that distinguishes nonpathogenic simian immunodeficiency virus (SIV infection in natural hosts from pathogenic SIV and HIV infection. To elucidate novel mechanisms downmodulating immune activation in natural hosts of SIV infection, we investigated natural killer T (NKT lymphocytes in sooty mangabeys. NKT lymphocytes are a potent immunoregulatory arm of the innate immune system that recognize glycolipid antigens presented on the nonpolymorphic MHC-class I-like CD1d molecules. In a cross-sectional analysis of 50 SIV-negative and 50 naturally SIV-infected sooty mangabeys, ligand alpha-galactosylceramide loaded CD1d tetramers co-staining with Valpha24-positive invariant NKT lymphocytes were detected at frequencies >or=0.002% of circulating T lymphocytes in approximately half of the animals. In contrast to published reports in Asian macaques, sooty mangabey NKT lymphocytes consisted of CD8(+ and CD4/CD8 double-negative T lymphocytes that were CXCR3-positive and CCR5-negative suggesting that they trafficked to sites of inflammation without being susceptible to SIV infection. Consistent with these findings, there was no difference in the frequency or phenotype of NKT lymphocytes between SIV-negative and SIV-infected sooty mangabeys. On stimulation with alpha-galactosylceramide loaded on human CD1d molecules, sooty mangabey NKT lymphocytes underwent degranulation and secreted IFN-gamma, TNF-alpha, IL-2, IL-13, and IL-10, indicating the presence of both effector and immunoregulatory functional capabilities. The unique absence of CD4(+ NKT lymphocytes in sooty mangabeys, combined with their IL-10 cytokine-secreting ability and preservation following SIV infection, raises the possibility that NKT lymphocytes might play a role in downmodulating immune activation in SIV-infected sooty mangabeys.

  18. The cytokine profile of human NKT cells and PBMCs is dependent on donor sex and stimulus.

    Science.gov (United States)

    Bernin, Hannah; Fehling, Helena; Marggraff, Claudia; Tannich, Egbert; Lotter, Hannelore

    2016-08-01

    Sex-related variations in natural killer T (NKT) cells may influence immunoregulation and outcome of infectious and autoimmune diseases. We analyzed sex-specific differences in peripheral blood NKTs and peripheral blood mononuclear cells (PBMCs) from men and women and determined the frequencies of NKT cells and their subpopulations [CD4(+); CD8(+); double negative (DN)] and the levels of cytokine production following stimulation with the NKT cell ligands α-Galactosylceramide (αGalCer) and Entamoeba histolytica lipopeptidephosphoglycan (Lotter et al. in PLoS Pathog 5(5):e1000434, 2009). Total and DN NKT cells were more abundant in women than in men. In women, αGalCer induced higher production of intracellular IFNγ, IL-4, IL-17 and TNF by CD4(+) and DN(+)NKT cells. Both ligands induced expression of multiple cytokines in PBMCs and influenced the ratio of NKT cell subpopulations during long-term culture. Although the sex-specific differences in frequencies of NKT cells and their subpopulations were marginal, the significant sex-specific differences in cytokine production might influence disease outcomes. PMID:26895635

  19. Potential role of NKT regulatory cell ligands for the treatment of immune mediated colitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Natural killer T lymphocytes (NKT) have been implicated in the regulation of autoimmune processes in both mice and humans. In response to stimuli, this subset of cells rapidly produces large amounts of cytokines thereby provoking immune responses, including protection against autoimmune diseases. NKT cells are present in all lymphoid compartments, but are most abundant in the liver and bone marrow. They are activated by interaction of their T-cell receptor with glycolipids presented by CD1d, a nonpolymorphic, major histocompatibility complex class Mike molecule expressed by antigen presenting cells. Several possible ligands for NKT cells have recently been suggested, p-glucosylceramide, a naturally occurring glycolipid, is a metabolic intermediate in the anabolic and catabolic pathways of complex glycosphingolipids. Like other p-glycolipids, p-glucosylceramide has an immunomodulatory effect in several immune mediated disorders, including immune mediated colitis. Due to the broad impact that NKT cells have on the immune system, there is intense interest in understanding how NKT cells are stimulated and the extent to which NKT cell responses can be controlled. These novel ligands are currently being evaluated in animal models of colitis. Here, we discuss strategies to alter NKT lymphocyte function in various settings and the potential clinical applications of natural glycolipids.

  20. Natural killer T (NKT cells accelerate Shiga toxin type 2 (Stx2 pathology in mice

    Directory of Open Access Journals (Sweden)

    Fumiko eObata

    2015-04-01

    Full Text Available Shiga toxin-producing Escherichia coli (STEC is a leading cause of childhood renal disease He-molytic Uremic Syndrome (HUS. The involvement of renal cytokines and chemokines is sus-pected to play a critical role in disease progression. In current article, we tested the hypothesis that NKT cells are involved in Stx2-induced pathology in vivo. To address this hypothesis we compared Stx2 toxicity in WT and CD1 knockout (KO mice. In CD1KO mice, which lack nat-ural killer T (NKT cells, Stx2-induced pathologies such as weight loss, renal failure, and death were delayed. In WT mice, Stx2-specific selective increase in urinary albumin occurs in later time points, and this was also delayed in NKT cell deficient mice. NKT cell-associated cytokines such as IL-2, IL-4, IFN-γ and IL-17 were detected in kidney lysates of Stx2-injected WT mice with the peak around 36 h after Stx2 injection. In CD1KO, there was a delay in the kinetics, and increases in these cytokines were observed 60 h post Stx2 injection. These data suggest that NKT cells accelerate Stx2-induced pathology in mouse kidneys. To determine the mechanism by which NKT cells promote Stx2-associated disease, in vitro studies were performed using murine renal cells. We found that murine glomerular endothelial cells and podocytes express functional CD1d molecules and can present exogenous antigen to NKT cells. Moreover, we observed the direct interaction between Stx2 and the receptor Gb3 on the surface of mouse renal cells by 3D STORM-TIRF which provides single molecule imaging. Collectively, these data suggest that Stx2 binds to Gb3 on renal cells and leads to aberrant CD1d-mediated NKT cell activation. Therefore, strategies targeting NKT cells could have a significant impact on Stx2-associated renal pathology in STEC disease.

  1. Flagellin Modulates the Function of Invariant NKT Cells From Patients With Asthma via Dendritic Cells

    OpenAIRE

    Shim, Jae-Uoong; Rhee, Joon-Haeng; Jeong, Ji-Ung; Koh, Young-Il

    2015-01-01

    Purpose Invariant natural killer T (iNKT) cells play a critical role in the pathogenesis of asthma. We previously reported the association between circulating Th2-like iNKT cells and lung function in asthma patients and the suppressive effect of Toll-like receptor 5 ligand flagellin B (FlaB) on asthmatic in a mouse model. Thus, we investigated whether FlaB modulates the function of circulating iNKT cells in asthmatic patients. Methods Peripheral blood mononuclear cells (PBMCs) were treated wi...

  2. Reduced iNKT cells numbers in type 1 diabetes patients and their first-degree relatives.

    Science.gov (United States)

    Beristain-Covarrubias, Nonantzin; Canche-Pool, Elsy; Gomez-Diaz, Rita; Sanchez-Torres, Luvia E; Ortiz-Navarrete, Vianney

    2015-12-01

    Type 1 diabetes (T1D) is an autoimmune disease that is characterized by the specific destruction of insulin-producing pancreatic β cells. Invariant natural killer T (iNKT) cells have been associated with development of T1D. Class I MHC-restricted T cell-associated molecule (CRTAM) is expressed on activated iNKT, CD8(+), and CD4(+) T cells, and it is associated with the pro-inflammatory profiles of these cells. Crtam gene expression in CD3(+) lymphocytes from non-obese diabetic (NOD) mice is associated with T1D onset. However, expression of CRTAM on T cells from patients with T1D has not yet been evaluated. We compared iNKT cell (CD3(+)Vα24(+)Vβ11(+)) numbers and CRTAM expression in a Mexican population with recent-onset T1D and their first-degree relatives with control families. Remarkably, we found lower iNKT cell numbers in T1D families, and we identified two iNKT cell populations in some of the families. One iNKT cell population expressed high iTCR levels (iNKT(hi)), whereas another expressed low levels (iNKT(lo)) and also expressed CRTAM. These findings support a probable genetic determinant of iNKT cell numbers and a possible role for these cells in T1D development. This study also suggests that CRTAM identifies recently activated iNKT lymphocytes.

  3. Innate recognition of cell wall β-glucans drives invariant Natural Killer T (iNKT) cell responses against fungi

    Science.gov (United States)

    Cohen, Nadia R.; Tatituri, Raju V.V.; Rivera, Amariliz; Watts, Gerald F.M.; Kim, Edy Y.; Chiba, Asako; Fuchs, Beth B.; Mylonakis, Eleftherios; Besra, Gurdyal S.; Levitz, Stuart M.; Brigl, Manfred; Brenner, Michael B.

    2016-01-01

    SUMMARY iNKT cells are innate T lymphocytes recognizing endogenous and foreign lipid antigens presented in the MHC-like molecule CD1d. The semi-invariant iNKT cell TCR can detect certain bacterial and parasitic lipids, and drive iNKT cell responses. How iNKT cells respond to fungi, however, is unknown. We found that CD1d-deficient mice, which lack iNKT cells, poorly control infection with the fungal pathogen Aspergillus fumigatus. Furthermore, A. fumigatus rapidly activates iNKT cells in vivo and in vitro in the presence of APCs. Surprisingly, despite a requirement for CD1d recognition, the anti-fungal iNKT cell response does not require fungal lipids. Instead, Dectin-1 and MyD88-mediated responses to β-1,3 glucans, major fungal cell-wall polysaccharides, trigger IL-12 production by APCs that drives self-reactive iNKT cells to secrete IFN-γ. Innate recognition of β-1,3 glucans also drives iNKT cell responses against Candida, Histoplasma and Alternaria, suggesting that this mechanism may broadly define the basis for anti-fungal iNKT cell responses. PMID:22100160

  4. Thymic and peripheral microenvironments differentially mediate development and maturation of iNKT cells by IL-15 transpresentation.

    Science.gov (United States)

    Castillo, Eliseo F; Acero, Luis F; Stonier, Spencer W; Zhou, Dapeng; Schluns, Kimberly S

    2010-10-01

    Invariant NKT (iNKT) cells are an innate type of T cells, which respond rapidly on activation. iNKT cells acquire these innate-like abilities during development; however, the signals driving development and functional maturation remain only partially understood. Because interleukin-15 (IL-15) is crucial for iNKT development and is delivered by transpresentation, we set out to identify the cell types providing IL-15 to developing iNKT cells and determine their role at the various states of development and maturation. We report here that transpresentation of IL-15 by parenchymal cells was crucial for generating normal number of iNKTs in the thymus, whereas both hematopoietic and parenchymal cells regulated iNKT cell numbers in the periphery, particularly in the liver. Specifically, dendritic cells contributed to peripheral iNKT cell numbers by up-regulating Bcl-2 expression and promoting extrathymic iNKT cell ex-pansion and their homeostatic proliferation. Whether IL-15 affects functional maturation of iNKT cells was also examined. In IL-15Rα(-/-) mice, CD44(High)NK1.1(+) iNKT cells displayed decreased T-bet expression and in response to α-galactosylceramide, had deficient interferon-γ expression. Such defects could be reversed by exogenous IL-15 signals. Overall, these studies identify stage-specific functions of IL-15, which are determined by the tissue microenvironment and elucidate the importance of IL-15 in functional maturation.

  5. CD1d expression and invariant NKT cell responses in herpesvirus infections

    Directory of Open Access Journals (Sweden)

    Rusung eTan

    2015-06-01

    Full Text Available Invariant natural killer T (iNKT cells are a highly conserved subset of unconventional T lymphocytes that express a canonical, semi-invariant T cell receptor (TCR and surface markers shared with the natural killer cell lineage. iNKT cells recognize exogenous and endogenous glycolipid antigens restricted by non-polymorphic CD1d molecules, and are highly responsive to the prototypical agonist, α-galactosylceramide. Upon activation, iNKT cells rapidly coordinate signaling between innate and adaptive immune cells through the secretion of proinflammatory cytokines, leading to the maturation of antigen-presenting cells and expansion of antigen-specific CD4+ and CD8+ T cells. Because of their potent immunoregulatory properties, iNKT cells have been extensively studied and are known to play a pivotal role in mediating immune responses against microbial pathogens including viruses. Here, we review evidence that herpesviruses manipulate CD1d expression to escape iNKT cell surveillance and establish lifelong latency in humans. Collectively, published findings suggest that iNKT cells play critical roles in anti-herpesvirus immune responses and could be harnessed therapeutically to limit viral infection and viral-associated disease.

  6. Foxp3 regulates ratio of Treg and NKT cells in a mouse model of asthma.

    Science.gov (United States)

    Lu, Yanming; Guo, Yinshi; Xu, Linyun; Li, Yaqin; Cao, Lanfang

    2015-05-01

    Chronic inflammatory disorder of the airways causes asthma. Regulatory T cells (Treg cells) and Natural killer T cells (NKT cells) both play critical roles in the pathogenesis of asthma. Activation of Treg cells requires Foxp3, whereas whether Foxp3 may regulate the ratio of Treg and NKT cells to affect asthma is uncertain. In an ovalbumin (OVA)-induced mouse model of asthma, we either increased Treg cells by lentivirus-mediated forced expression of exogenous Foxp3, or increased NKT cells by stimulation with its activator α-GalCer. We found that the CD4+CD25+ Treg cells increased by forced Foxp3 expression, and decreased by α-GalCer, while the CD3+CD161+ NKT cells decreased by forced Foxp3 expression, and increased by α-GalCer. Moreover, forced Foxp3 expression, but not α-GalCer, significantly alleviated the hallmarks of asthma. Furthermore, forced Foxp3 increased levels of IL_10 and TGFβ1, and α-GalCer increased levels of IL_4 and INFγ in the OVA-treated lung. Taken together, our study suggests that Foxp3 may activate Treg cells and suppress NKT cells in asthma. Treg and NKT cells may antagonize the effects of each other in asthma. PMID:25636804

  7. Antitumor Immunity Produced by the Liver Kupffer Cells, NK Cells, NKT Cells, and CD8+ CD122+ T Cells

    OpenAIRE

    Shuhji Seki; Hiroyuki Nakashima; Masahiro Nakashima; Manabu Kinoshita

    2011-01-01

    Mouse and human livers contain innate immune leukocytes, NK cells, NKT cells, and macrophage-lineage Kupffer cells. Various bacterial components, including Toll-like receptor (TLR) ligands and an NKT cell ligand ( α -galactocylceramide), activate liver Kupffer cells, which produce IL-1, IL-6, IL-12, and TNF. IL-12 activates hepatic NK cells and NKT cells to produce IFN- γ , which further activates hepatic T cells, in turn activating phagocytosis and cytokine production by Kupffer cells in a p...

  8. SAP expression in invariant NKT cells is required for cognate help to support B-cell responses.

    Science.gov (United States)

    Detre, Cynthia; Keszei, Marton; Garrido-Mesa, Natividad; Kis-Toth, Katalin; Castro, Wilson; Agyemang, Amma F; Veerapen, Natacha; Besra, Gurdyal S; Carroll, Michael C; Tsokos, George C; Wang, Ninghai; Leadbetter, Elizabeth A; Terhorst, Cox

    2012-07-01

    One of the manifestations of X-linked lymphoproliferative disease (XLP) is progressive agammaglobulinemia, caused by the absence of a functional signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) in T, invariant natural killer T (NKT) cells and NK cells. Here we report that α-galactosylceramide (αGalCer) activated NKT cells positively regulate antibody responses to haptenated protein antigens at multiple checkpoints, including germinal center formation and affinity maturation. Whereas NKT cell-dependent B cell responses were absent in SAP(-/-).B6 mice that completely lack NKT cells, the small number of SAP-deficient NKT cells in SAP(-/-).BALB/c mice adjuvated antibody production, but not the germinal center reaction. To test the hypothesis that SAP-deficient NKT cells can facilitate humoral immunity, SAP was deleted after development in SAP(fl/fl).tgCreERT2.B6 mice. We find that NKT cell intrinsic expression of SAP is dispensable for noncognate helper functions, but is critical for providing cognate help to antigen-specific B cells. These results demonstrate that SLAM-family receptor-regulated cell-cell interactions are not limited to T-B cell conjugates. We conclude that in the absence of SAP, several routes of NKT cell-mediated antibody production are still accessible. The latter suggests that residual NKT cells in XLP patients might contribute to variations in dysgammaglobulinemia.

  9. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production.

    LENUS (Irish Health Repository)

    Lynch, Lydia

    2012-09-21

    Invariant natural killer T (iNKT) cells are evolutionarily conserved innate T cells that influence inflammatory responses. We have shown that iNKT cells, previously thought to be rare in humans, were highly enriched in human and murine adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were depleted, correlating with proinflammatory macrophage infiltration. iNKT cell numbers were restored in mice and humans after weight loss. Mice lacking iNKT cells had enhanced weight gain, larger adipocytes, fatty livers, and insulin resistance on a high-fat diet. Adoptive transfer of iNKT cells into obese mice or in vivo activation of iNKT cells via their lipid ligand, alpha-galactocylceramide, decreased body fat, triglyceride levels, leptin, and fatty liver and improved insulin sensitivity through anti-inflammatory cytokine production by adipose-derived iNKT cells. This finding highlights the potential of iNKT cell-targeted therapies, previously proven to be safe in humans, in the management of obesity and its consequences.

  10. Restored Circulating Invariant NKT Cells Are Associated with Viral Control in Patients with Chronic Hepatitis B

    Science.gov (United States)

    Jiang, Xiaotao; Zhang, Mingxia; Lai, Qintao; Huang, Xuan; Li, Yongyin; Sun, Jian; Abbott, William G.H.; Ma, Shiwu; Hou, Jinlin

    2011-01-01

    Invariant NKT (iNKT) cells are involved in the pathogenesis of various infectious diseases. However, their role in hepatitis B virus (HBV) infection is not fully understood, especially in human species. In this study, 35 chronic hepatitis B (CHB) patients, 25 inactive carriers (IC) and 36 healthy controls (HC) were enrolled and the proportions of circulating iNKT cells in fresh isolated peripheral blood mononuclear cells (PBMC) were detected by flow cytometry. A longitudinal analysis was also conducted in 19 CHB patients who received antiviral therapy with telbivudine. Thereafter, the immune functions of iNKT cells were evaluated by cytokine secretion and a two-chamber technique. The median frequency of circulating iNKT cells in CHB patients (0.13%) was lower than that in HC (0.24%, P = 0.01) and IC (0.19%, P = 0.02), and increased significantly during antiviral therapy with telbivudine (P = 0.0176). The expressions of CC chemokine receptor 5 (CCR5) and CCR6 were dramatically higher on iNKT cells (82.83%±9.87%, 67.67%±16.83% respectively) than on conventional T cells (30.5%±5.65%, 14.02%±5.92%, both P<0.001) in CHB patients. Furthermore, iNKT cells could migrate toward the CC chemokine ligand 5. Patients with a high ratio (≥1.0) of CD4−/CD4+ iNKT cells at baseline had a higher rate (58.33%) of HBeAg seroconversion than those with a low ratio (<1.0, 0%, P = 0.0174). In conclusion, there is a low frequency of peripheral iNKT cells in CHB patients, which increases to normal levels with viral control. The ratio of CD4−/CD4+ iNKT cells at baseline may be a useful predictor for HBeAg seroconversion in CHB patients on telbivudine therapy. PMID:22194934

  11. RASAL3, a novel hematopoietic RasGAP protein, regulates the number and functions of NKT cells.

    Science.gov (United States)

    Saito, Suguru; Kawamura, Toshihiko; Higuchi, Masaya; Kobayashi, Takahiro; Yoshita-Takahashi, Manami; Yamazaki, Maya; Abe, Manabu; Sakimura, Kenji; Kanda, Yasuhiro; Kawamura, Hiroki; Jiang, Shuying; Naito, Makoto; Yoshizaki, Takumi; Takahashi, Masahiko; Fujii, Masahiro

    2015-05-01

    Ras GTPase-activating proteins negatively regulate the Ras/Erk signaling pathway, thereby playing crucial roles in the proliferation, function, and development of various types of cells. In this study, we identified a novel Ras GTPase-activating proteins protein, RASAL3, which is predominantly expressed in cells of hematopoietic lineages, including NKT, B, and T cells. We established systemic RASAL3-deficient mice, and the mice exhibited a severe decrease in NKT cells in the liver at 8 weeks of age. The treatment of RASAL3-deficient mice with α-GalCer, a specific agonist for NKT cells, induced liver damage, but the level was less severe than that in RASAL3-competent mice, and the attenuated liver damage was accompanied by a reduced production of interleukin-4 and interferon-γ from NKT cells. RASAL3-deficient NKT cells treated with α-GalCer in vitro presented augmented Erk phosphorylation, suggesting that there is dysregulated Ras signaling in the NKT cells of RASAL3-deficient mice. Taken together, these results suggest that RASAL3 plays an important role in the expansion and functions of NKT cells in the liver by negatively regulating Ras/Erk signaling, and might be a therapeutic target for NKT-associated diseases.

  12. Activation of murine invariant NKT cells promotes susceptibility to candidiasis by IL-10 induced modulation of phagocyte antifungal activity.

    Science.gov (United States)

    Haraguchi, Norihiro; Kikuchi, Norihiro; Morishima, Yuko; Matsuyama, Masashi; Sakurai, Hirofumi; Shibuya, Akira; Shibuya, Kazuko; Taniguchi, Masaru; Ishii, Yukio

    2016-07-01

    Invariant NKT (iNKT) cells play an important role in a variety of antimicrobial immune responses due to their ability to produce high levels of immune-modulating cytokines. Here, we investigated the role of iNKT cells in host defense against candidiasis using Jα18-deficient mice (Jα18(-/-) ), which lack iNKT cells. Jα18(-/-) mice were more resistant to the development of lethal candidiasis than wild-type (WT) mice. In contrast, treatment of WT mice with the iNKT cell activating ligand α-galactosylceramide markedly enhanced their mortality after infection with Candida albicans. Serum IL-10 levels were significantly elevated in WT mice in response to infection with C. albicans. Futhermore, IL-10 production increased after in vitro coculture of peritoneal macrophages with iNKT cells and C. albicans. The numbers of peritoneal macrophages, the production of IL-1β and IL-18, and caspase-1 activity were also significantly elevated in Jα18(-/-) mice after infection with C. albicans. The adoptive transfer of iNKT cells or exogenous administration of IL-10 into Jα18(-/-) reversed susceptibility to candidiasis to the level of WT mice. These results suggest that activation of iNKT cells increases the initial severity of C. albicans infection, most likely mediated by IL-10 induced modulation of macrophage antifungal activity. PMID:27151377

  13. Innate-like control of human iNKT cell autoreactivity via the hypervariable CDR3beta loop.

    Directory of Open Access Journals (Sweden)

    Gediminas Matulis

    Full Text Available Invariant Natural Killer T cells (iNKT are a versatile lymphocyte subset with important roles in both host defense and immunological tolerance. They express a highly conserved TCR which mediates recognition of the non-polymorphic, lipid-binding molecule CD1d. The structure of human iNKT TCRs is unique in that only one of the six complementarity determining region (CDR loops, CDR3beta, is hypervariable. The role of this loop for iNKT biology has been controversial, and it is unresolved whether it contributes to iNKT TCR:CD1d binding or antigen selectivity. On the one hand, the CDR3beta loop is dispensable for iNKT TCR binding to CD1d molecules presenting the xenobiotic alpha-galactosylceramide ligand KRN7000, which elicits a strong functional response from mouse and human iNKT cells. However, a role for CDR3beta in the recognition of CD1d molecules presenting less potent ligands, such as self-lipids, is suggested by the clonal distribution of iNKT autoreactivity. We demonstrate that the human iNKT repertoire comprises subsets of greatly differing TCR affinity to CD1d, and that these differences relate to their autoreactive functions. These functionally different iNKT subsets segregate in their ability to bind CD1d-tetramers loaded with the partial agonist alpha-linked glycolipid antigen OCH and structurally different endogenous beta-glycosylceramides. Using surface plasmon resonance with recombinant iNKT TCRs and different ligand-CD1d complexes, we demonstrate that the CDR3beta sequence strongly impacts on the iNKT TCR affinity to CD1d, independent of the loaded CD1d ligand. Collectively our data reveal a crucial role for CDR3beta for the function of human iNKT cells by tuning the overall affinity of the iNKT TCR to CD1d. This mechanism is relatively independent of the bound CD1d ligand and thus forms the basis of an inherent, CDR3beta dependent functional hierarchy of human iNKT cells.

  14. Colonic inflammation in mice is improved by cigarette smoke through iNKT cells recruitment.

    Directory of Open Access Journals (Sweden)

    Muriel Montbarbon

    Full Text Available Cigarette smoke (CS protects against intestinal inflammation during ulcerative colitis. Immunoregulatory mechanisms sustaining this effect remain unknown. The aim of this study was to assess the effects of CS on experimental colitis and to characterize the intestinal inflammatory response at the cellular and molecular levels. Using the InExpose® System, a smoking device accurately reproducing human smoking habit, we pre-exposed C57BL/6 mice for 2 weeks to CS, and then we induced colitis by administration of dextran sodium sulfate (DSS. This system allowed us to demonstrate that CS exposure improved colonic inflammation (significant decrease in clinical score, body weight loss and weight/length colonic ratio. This improvement was associated with a significant decrease in colonic proinflammatory Th1/Th17 cytokine expression, as compared to unexposed mice (TNF (p=0.0169, IFNγ (p<0.0001, and IL-17 (p=0.0008. Smoke exposure also induced an increased expression of IL-10 mRNA (p=0.0035 and a marked recruitment of iNKT (invariant Natural Killer T; CD45+ TCRβ+ CD1d tetramer+ cells in the colon of DSS-untreated mice. Demonstration of the role of iNKT cells in CS-dependent colitis improvement was performed using two different strains of NKT cells deficient mice. Indeed, in Jα18KO and CD1dKO animals, CS exposure failed to induce significant regulation of DSS-induced colitis both at the clinical and molecular levels. Thus, our study demonstrates that iNKT cells are pivotal actors in the CS-dependent protection of the colon. These results highlight the role of intestinal iNKT lymphocytes and their responsiveness to environmental stimuli. Targeting iNKT cells would represent a new therapeutic way for inflammatory bowel diseases.

  15. Diabetes Mellitus Directs NKT Cells Toward Type 2 and Regulatory Phenotype / Diabetes Melitus Usmerava Diferencijaciju NKT Celija U Pravcu Tip 2 I Regulatornog Fenotipa

    Directory of Open Access Journals (Sweden)

    Gajovic Nevena

    2016-03-01

    Full Text Available Diabetes mellitus is chronic disorder characterized by hyperglycaemia. Hyperglycaemia induces mitochondrial dysfunction, enhances oxidative stress and thus promotes reactive oxygen species (ROS production. Earlier studies suggested that reactive oxygen species (ROS are involved in the pathogenesis of many diseases. Previous studies have revealed that hyperglycaemia changes the functional phenotype of monocytes, macrophages, neutrophils, NK cells and CD8+ T cells. The aim of this study was to investigate whether diabetes affects the functional phenotype of NKT cells.

  16. iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy.

    Science.gov (United States)

    Lynch, Lydia; Hogan, Andrew E; Duquette, Danielle; Lester, Chantel; Banks, Alexander; LeClair, Katherine; Cohen, David E; Ghosh, Abhisek; Lu, Bing; Corrigan, Michelle; Stevanovic, Darko; Maratos-Flier, Eleftheria; Drucker, Daniel J; O'Shea, Donal; Brenner, Michael

    2016-09-13

    Adipose-resident invariant natural killer T (iNKT) cells are key players in metabolic regulation. iNKT cells are innate lipid sensors, and their activation, using their prototypic ligand α-galactosylceramide (αGalCer), induces weight loss and restores glycemic control in obesity. Here, iNKT activation induced fibroblast growth factor 21 (FGF21) production and thermogenic browning of white fat. Complete metabolic analysis revealed that iNKT cell activation induced increased body temperature, V02, VC02, and fatty acid oxidation, without affecting food intake or activity. FGF21 induction played a major role in iNKT cell-induced weight loss, as FGF21 null mice lost significantly less weight after αGalCer treatment. The glucagon-like peptide 1 (GLP-1) receptor agonist, liraglutide, also activated iNKT cells in humans and mice. In iNKT-deficient mice, liraglutide promoted satiety but failed to induce FGF21, resulting in less weight loss. These findings reveal an iNKT cell-FGF21 axis that defines a new immune-mediated pathway that could be targeted for glycemic control and weight regulation. PMID:27593966

  17. NKT cell self-reactivity: evolutionary master key of immune homeostasis?

    Institute of Scientific and Technical Information of China (English)

    Shohreh Issazadeh-Navikas

    2012-01-01

    Complex immune responses have evolved to protect multicellular organisms against the invasion of pathogens.This has exerted strong developmental pressure for specialized functions that can also limit damage to self-tissue.Two arms of immunity,the innate and adaptive immune systems,have evolved for quick,non-specific immune responses to pathogens and more efficient,long-lasting ones upon specific recognition of recurrent pathogens.Specialized cells have arisen as the sentinels of these functions,including macrophages,natural killer (NK),and T and B-lymphocytes.Interestingly,a population of immune cells that can exert both of these complex functions,NKT cells,not only share common functions but also exhibit shared cell surface markers of cells of both arms of the Immune system.These features,in combination with sophisticated maintenance of immune homeostasis,will be discussed.The recent finding of self-peptide reactivity of NKT cells in the context of CD1d,with capacity to regulate multiple autoimmune and inflammatory conditions,motivates the current proposal that self-reactive NKT cells might be the ancestral link between present NK and T cells.Their parallel selection through evolution by higher vertebrates could be related to their central function as master regulators of immune homeostasis that in part is shared with regulatory T cells,Hypothetical views on how self-reactive NKT cells secure such a central role will also be proposed.

  18. Increase of NK-T cells in aged depressed patients not treated with antidepressive drugs

    NARCIS (Netherlands)

    Flentge, F; van den Berg, MD; Bouhuys, AL; The, HT

    2000-01-01

    Background: A change in number and/or activity of natural killer cells has repeatedly been reported in depressive illness. Much less attention has yet been given to the subgroup of natural killer cells that are positive Sor the T-cell marker CD3 (NK-T cells). These cells possibly have important immu

  19. Lack of PD-L1 expression by iNKT cells improves the course of influenza A infection.

    Directory of Open Access Journals (Sweden)

    Hadi Maazi

    Full Text Available There is evidence indicating that invariant Natural Killer T (iNKT cells play an important role in defense against influenza A virus (IAV. However, the effect of inhibitory receptor, programmed death-1 (PD-1, and its ligands, programmed death ligand (PD-L 1 and 2 on iNKT cells in protection against IAV remains to be elucidated. Here we investigated the effects of these co-stimulatory molecules on iNKT cells in the response to influenza. We discovered that compare to the wild type, PD-L1 deficient mice show reduced sensitivity to IAV infection as evident by reduced weight loss, decreased pulmonary inflammation and cellular infiltration. In contrast, PD-L2 deficient mice showed augmented weight loss, pulmonary inflammation and cellular infiltration compare to the wild type mice after influenza infection. Adoptive transfer of iNKT cells from wild type, PD-L1 or PD-L2 deficient mice into iNKT cell deficient mice recapitulated these findings. Interestingly, in our transfer system PD-L1(-/--derived iNKT cells produced high levels of interferon-gamma whereas PD-L2(-/--derived iNKT cells produced high amounts of interleukin-4 and 13 suggesting a role for these cytokines in sensitivity to influenza. We identified that PD-L1 negatively regulates the frequency of iNKT cell subsets in the lungs of IAV infected mice. Altogether, these results demonstrate that lack of PD-L1 expression by iNKT cells reduces the sensitivity to IAV and that the presence of PD-L2 is important for dampening the deleterious inflammatory responses after IAV infection. Our findings potentially have clinical implications for developing new therapies for influenza.

  20. Invariant Natural Killer T (iNKT Cells Prevent Autoimmunity, but Induce Pulmonary Inflammation in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Nanna Siegmann

    2014-06-01

    Full Text Available Background/Aims: Inflammation is a major and critical component of the lung pathology in the hereditary disease cystic fibrosis. The molecular mechanisms of chronic inflammation in cystic fibrosis require definition. Methods: We used several genetic mouse models to test a role of iNKT cells and ceramide in pulmonary inflammation of cystic fibrosis mice. Inflammation was determined by the pulmonary cytokine profil and the abundance of inflammatory cells in the lung. Results: Here we provide a new concept how inflammation in the lung of individuals with cystic fibrosis is initiated. We show that in cystic fibrosis mice the mutation in the Cftr gene provokes a significant up-regulation of iNKT cells in the lung. Accumulation of iNKT cells serves to control autoimmune disease, which is triggered by a ceramide-mediated induction of cell death in CF organs. Autoimmunity becomes in particular overt in cystic fibrosis mice lacking iNKT cells and although suppression of the autoimmune response by iNKT cells is beneficial, IL-17+ iNKT cells attract macrophages and neutrophils to CF lungs resulting in chronic inflammation. Genetic deletion of iNKT cells in cystic fibrosis mice prevents inflammation in CF lungs. Conclusion: Our data demonstrate an important function of iNKT cells in the chronic inflammation affecting cystic fibrosis lungs. iNKT cells suppress the auto-immune response induced by ceramide-mediated death of epithelial cells in CF lungs, but also induce a chronic pulmonary inflammation.

  1. Human invariant NKT cell subsets differentially promote differentiation, antibody production, and T cell stimulation by B cells in vitro.

    OpenAIRE

    O'Reilly, Vincent

    2013-01-01

    PUBLISHED Invariant NK T (iNKT) cells can provide help for B cell activation and Ab production. Because B cells are also capable of cytokine production, Ag presentation, and T cell activation, we hypothesized that iNKT cells will also influence these activities. Furthermore, subsets of iNKT cells based on CD4 and CD8 expression that have distinct functional activities may differentially affect B cell functions. We investigated the effects of coculturing expanded human CD4(+), CD8α(+), and ...

  2. Regulation of NKT cell-mediated immune responses to tumours and liver inflammation by mitochondrial PGAM5-Drp1 signalling

    OpenAIRE

    Kang, Young Jun; Bang, Bo-Ram; Han, Kyung Ho; Hong, Lixin; Shim, Eun-Jin; Ma, Jianhui; Lerner, Richard A.; Otsuka, Motoyuki

    2015-01-01

    The receptor-interacting protein kinase 3 (RIPK3) plays crucial roles in programmed necrosis and innate inflammatory responses. However, a little is known about the involvement of RIPK3 in NKT cell-mediated immune responses. Here, we demonstrate that RIPK3 plays an essential role in NKT cell function via activation of the mitochondrial phosphatase phosphoglycerate mutase 5 (PGAM5). RIPK3-mediated activation of PGAM5 promotes the expression of cytokines by facilitating nuclear translocation of...

  3. Human iNKT Cells Promote Protective Inflammation by Inducing Oscillating Purinergic Signaling in Monocyte-Derived DCs.

    Science.gov (United States)

    Xu, Xuequn; Pocock, Ginger M; Sharma, Akshat; Peery, Stephen L; Fites, J Scott; Felley, Laura; Zarnowski, Robert; Stewart, Douglas; Berthier, Erwin; Klein, Bruce S; Sherer, Nathan M; Gumperz, Jenny E

    2016-09-20

    Invariant natural killer T (iNKT) cells are innate T lymphocytes that promote host defense against a variety of microbial pathogens. Whether microbial ligands are required for their protective effects remains unclear. Here, we show that iNKT cells stimulate human-monocyte-derived dendritic cells (DCs) to produce inflammatory mediators in a manner that does not require the presence of microbial compounds. Interleukin 2 (IL-2)-exposed iNKT cells selectively induced repeated cytoplasmic Ca(2+) fluxes in DCs that were dependent on signaling by the P2X7 purinergic receptor and mediated by ATP released during iNKT-DC interactions. Exposure to iNKT cells led to DC cyclooxygenase 2 (PTGS2) gene transcription, and release of PGE2 that was associated with vascular permeabilization in vivo. Additionally, soluble factors were released that induced neutrophil recruitment and activation and enhanced control of Candida albicans. These results suggest that sterile interactions between iNKT cells and monocyte-derived DCs lead to the production of non-redundant inflammatory mediators that promote neutrophil responses. PMID:27653689

  4. NKT cell self-reactivity: evolutionary master key of immune homeostasis?

    DEFF Research Database (Denmark)

    Navikas, Shohreh

    2011-01-01

    through evolution by higher vertebrates could be related to their central function as master regulators of immune homeostasis that in part is shared with regulatory T cells. Hypothetical views on how self-reactive NKT cells secure such a central role will also be proposed....... for quick, non-specific immune responses to pathogens and more efficient, long-lasting ones upon specific recognition of recurrent pathogens. Specialized cells have arisen as the sentinels of these functions, including macrophages, natural killer (NK), and T and B-lymphocytes. Interestingly, a population...... of immune cells that can exert both of these complex functions, NKT cells, not only share common functions but also exhibit shared cell surface markers of cells of both arms of the immune system. These features, in combination with sophisticated maintenance of immune homeostasis, will be discussed...

  5. A case of primary pulmonary NK/T cell lymphoma presenting as pneumonia.

    Science.gov (United States)

    Lee, Sangho; Shin, Bongkyung; Yoon, Hyungseok; Lee, Jung Yeon; Chon, Gyu Rak

    2016-01-01

    Primary pulmonary lymphoma, particularly non-B cell lymphomas involving lung parenchyma, is very rare. A 46-year-old male was admitted to the hospital with fever and cough. Chest X-ray showed left lower lobe consolidation, which was considered pneumonia. However, because the patient showed no response to empirical antibiotic therapy, bronchoscopic biopsy was performed for proper diagnosis. The biopsied specimen showed infiltrated atypical lymphocytes with angiocentric appearance. On immunohistochemical staining, these atypical cells were positive for CD3, CD30, CD56, MUM-1, and granzyme B, and labeled for Epstein-Barr virus encoded RNA in situ hybridization. These findings were consistent with NK/T cell lymphoma. We report on a case of primary pulmonary NK/T cell lymphoma presenting as pneumonic symptoms and review the literature on the subject.

  6. 天然杀伤T细胞对多树突状细胞的调节作用%Modulation of DC function by NKT cells

    Institute of Scientific and Technical Information of China (English)

    杨熙

    2011-01-01

    Both dendritic cells (DC) and natural killer T (NKT) cells are small cell populations related to immune regulation.The interaction between these two types of immune cells is a hot topic in current study on immunobiology.Recent data not only demonstrate that DC can influence the activation/function of NKT cells but also suggest that NKT cells can feedback on DC,thus modulating the phenotype and function of DC.This two-way interaction between NKT cells and DC may play an important role in the linkage of innate and adaptive immune responses.

  7. Cross-activating invariant NKT cells and kupffer cells suppress cholestatic liver injury in a mouse model of biliary obstruction.

    Directory of Open Access Journals (Sweden)

    Caroline C Duwaerts

    Full Text Available Both Kupffer cells and invariant natural killer T (iNKT cells suppress neutrophil-dependent liver injury in a mouse model of biliary obstruction. We hypothesize that these roles are interdependent and require iNKT cell-Kupffer cell cross-activation. Female, wild-type and iNKT cell-deficient C57Bl/6 mice were injected with magnetic beads 3 days prior to bile duct ligation (BDL in order to facilitate subsequent Kupffer cell isolation. On day three post-BDL, the animals were euthanized and the livers dissected. Necrosis was scored; Kupffer cells were isolated and cell surface marker expression (flow cytometry, mRNA expression (qtPCR, nitric oxide (NO (. production (Griess reaction, and protein secretion (cytometric bead-array or ELISAs were determined. To address the potential role of NO (. in suppressing neutrophil accumulation, a group of WT mice received 1400W, a specific inducible nitric oxide synthase (iNOS inhibitor, prior to BDL. To clarify the mechanisms underlying Kupffer cell-iNKT cell cross-activation, WT animals were administered anti-IFN-γ or anti-lymphocyte function-associated antigen (LFA-1 antibody prior to BDL. Compared to their WT counterparts, Kupffer cells obtained from BDL iNKT cell-deficient mice expressed lower iNOS mRNA levels, produced less NO (. , and secreted more neutrophil chemoattractants. Both iNOS inhibition and IFN-γ neutralization increased neutrophil accumulation in the livers of BDL WT mice. Anti-LFA-1 pre-treatment reduced iNKT cell accumulation in these same animals. These data indicate that the LFA-1-dependent cross-activation of iNKT cells and Kupffer cells inhibits neutrophil accumulation and cholestatic liver injury.

  8. Papel de las células nkt invariantes en la respuesta inmune anti-viral

    Directory of Open Access Journals (Sweden)

    Alejandro Román

    2006-06-01

    Full Text Available Las células T asesinas naturales con receptor de células T invariante y restringidas por la molécula CD1d (iNKT son un subgrupo de linfocitos con potente actividad inmunorreguladora; su respuesta casi inmediata y la capacidad de producir citoquinas tanto Th1 como Th2 son factores determinantes en el desarrollo de la respuesta inmune innata y adaptativa. El papel fisiológico de las células iNKT se ha documentado ampliamente en la respuesta anti-tumoral, el desarrollo de la tolerancia en los órganos inmunoprivilegiados y el control de las reacciones autoinmunes. A pesar de la demostrada potencia inmunomoduladora de las células iNKT, hasta el momento se conoce poco de su acción en la respuesta inmune anti-infecciosa, en particular en el ser humano y contra los virus patógenos. Este artículo sintetiza los resultados de una búsqueda en las principales bases de datos biomédicas (Pubmed, Medline y OVID, e incluye los estudios realizados para caracterizar estas células y evaluar su papel en la interacción del hospedero con los virus. Las células iNKT participan en la respuesta inmune antiviral, aunque de una manera diferente según el tipo de virus; incluso, podrían estar comprometidas en los daños mediados por mecanismos inmunes. En el ser humano, las células iNKT son aparentemente esenciales en la respuesta inmune contra el virus Varicela Zoster, mientras que todavía hay controversia sobre su función en el control de otros virus. Los modelos animales han aportado las primeras evidencias sobre el potencial de la manipulación terapéutica específica de este subgrupo de linfocitos.

  9. Papel de las células nkt invariantes en la respuesta inmune anti-viral.

    Directory of Open Access Journals (Sweden)

    Alejandro Román

    2009-11-01

    Full Text Available Las células T asesinas naturales con receptor de células T invariante y restringidas por la molécula CD1d (iNKT son un subgrupo de linfocitos con potente actividad inmunorreguladora; su respuesta casi inmediata y la capacidad de producir citoquinas tanto Th1 como Th2 son factores determinantes en el desarrollo de la respuesta inmune innata y adaptativa. El papel fisiológico de las células iNKT se ha documentado ampliamente en la respuesta anti-tumoral, el desarrollo de la tolerancia en los órganos inmunoprivilegiados y el control de las reacciones autoinmunes. A pesar de la demostrada potencia inmunomoduladora de las células iNKT, hasta el momento se conoce poco de su acción en la respuesta inmune anti-infecciosa, en particular en el ser humano y contra los virus patógenos. Este artículo sintetiza los resultados de una búsqueda en las principales bases de datos biomédicas (Pubmed, Medline y OVID, e incluye los estudios realizados para caracterizar estas células y evaluar su papel en la interacción del hospedero con los virus. Las células iNKT participan en la respuesta inmune antiviral, aunque de una manera diferente según el tipo de virus; incluso, podrían estar comprometidas en los daños mediados por mecanismos inmunes. En el ser humano, las células iNKT son aparentemente esenciales en la respuesta inmune contra el virus Varicela Zoster, mientras que todavía hay controversia sobre su función en el control de otros virus. Los modelos animales han aportado las primeras evidencias sobre el potencial de la manipulación terapéutica específica de este subgrupo de linfocitos.

  10. Differential requirement for the CD45 splicing regulator hnRNPLL for accumulation of NKT and conventional T cells.

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    Mehmet Yabas

    Full Text Available Natural killer T (NKT cells represent an important regulatory T cell subset that develops in the thymus and contains immature (NK1.1(lo and mature (NK1.1(hi cell subsets. Here we show in mice that an inherited mutation in heterogeneous ribonucleoprotein L-like protein (hnRNPLL(thunder, that shortens the survival of conventional T cells, has no discernible effect on NKT cell development, homeostasis or effector function. Thus, Hnrpll deficiency effectively increases the NKT∶T cell ratio in the periphery. However, Hnrpll mutation disrupts CD45RA, RB and RC exon silencing of the Ptprc mRNA in both NKT and conventional T cells, and leads to a comparably dramatic shift to high molecular weight CD45 isoforms. In addition, Hnrpll mutation has a cell intrinsic effect on the expression of the developmentally regulated cell surface marker NK1.1 on NKT cells in the thymus and periphery but does not affect cell numbers. Therefore our results highlight both overlapping and divergent roles for hnRNPLL between conventional T cells and NKT cells. In both cell subsets it is required as a trans-acting factor to regulate alternative splicing of the Ptprc mRNA, but it is only required for survival of conventional T cells.

  11. Spontaneous focal activation of invariant natural killer T (iNKT cells in mouse liver and kidney

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    Zeng Jia

    2010-11-01

    Full Text Available Abstract Background Invariant natural killer T (iNKT cells differ from other T cells by their hyperactive effector T-cell status, in addition to the expression of NK lineage receptors and semi-invariant T-cell receptors. It is generally agreed that the immune phenotype of iNKT cells is maintained by repeated activation in peripheral tissues although no explicit evidence for such iNKT cell activity in vivo has so far been reported. Results We used an interferon (IFN-γ-inducible cytoplasmic protein, Irga6, as a histological marker for local IFN-γ production. Irga6 was intensely expressed in small foci of liver parenchymal cells and kidney tubular epithelium. Focal Irga6 expression was unaffected by germ-free status or loss of TLR signalling and was totally dependent on IFN-γ secreted by T cells in the centres of expression foci. These were shown to be iNKT cells by diagnostic T cell receptor usage and their activity was lost in both CD1 d and Jα-deficient mice. Conclusions This is the first report that supplies direct evidence for explicit activation events of NKT cells in vivo and raises issues about the triggering mechanism and consequences for immune functions in liver and kidney.

  12. Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity.

    LENUS (Irish Health Repository)

    Lynch, Lydia

    2012-02-01

    Invariant NKT (iNKT) cells recognize lipid antigens presented by CD1d and respond rapidly by killing tumor cells and release cytokines that activate and regulate adaptive immune responses. They are essential for tumor rejection in various mouse models, but clinical trials in humans involving iNKT cells have been less successful, partly due to their rarity in humans compared with mice. Here we describe an accumulation of functional iNKT cells in human omentum, a migratory organ with healing properties. Analysis of 39 omental samples revealed that T cells are the predominant lymphoid cell type and of these, 10% expressed the invariant Valpha24Jalpha18 TCR chain, found on iNKT cells, higher than in any other human organ tested to date. About 15% of omental hematopoietic cells expressed CD1d, compared with 1% in blood (p<0.001). Enriched omental iNKT cells killed CD1d(+) targets and released IFN-gamma and IL-4 upon activation. Omental iNKT-cell frequencies were lower in patients with severe obesity (p=0.005), and with colorectal carcinoma (p=0.004) compared with lean healthy subjects. These data suggest a novel role for the omentum in immune regulation and tumor immunity and identify it as a potential source of iNKT cells for therapeutic use.

  13. Activated iNKT cells promote memory CD8+ T cell differentiation during viral infection.

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    Emma C Reilly

    Full Text Available α-Galactosylceramide (α-GalCer is the prototypical lipid ligand for invariant NKT cells. Recent studies have proposed that α-GalCer is an effective adjuvant in vaccination against a range of immune challenges, however its mechanism of action has not been completely elucidated. A variety of delivery methods have been examined including pulsing dendritic cells with α-GalCer to optimize the potential of α-GalCer. These methods are currently being used in a variety of clinical trials in patients with advanced cancer but cannot be used in the context of vaccine development against pathogens due to their complexity. Using a simple delivery method, we evaluated α-GalCer adjuvant properties, using the mouse model for cytomegalovirus (MCMV. We measured several key parameters of the immune response to MCMV, including inflammation, effector, and central memory CD8(+ T cell responses. We found that α-GalCer injection at the time of the infection decreases viral titers, alters the kinetics of the inflammatory response, and promotes both increased frequencies and numbers of virus-specific memory CD8(+ T cells. Overall, our data suggest that iNKT cell activation by α-GalCer promotes the development of long-term protective immunity through increased fitness of central memory CD8(+ T cells, as a consequence of reduced inflammation.

  14. Increased Numbers of NK Cells, NKT-Like Cells, and NK Inhibitory Receptors in Peripheral Blood of Patients with Chronic Obstructive Pulmonary Disease

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    Ying Tang

    2013-01-01

    Full Text Available T cells and B cells participate in the pathogenesis of COPD. Currently, NK cells and NKT cells have gained increasing attention. In the present study, 19 COPD patients and 12 healthy nonsmokers (HNS were recruited, and their pulmonary function was assessed. The frequencies of CD3+ T, CD4+ T, CD8+ T, B, NK, and NKT-like cells were determined using flow cytometry. The frequencies of spontaneous and inducible IFN-γ+ or CD107a+ NK and NKT-like cells as well as activating or inhibitory receptors were also detected. The potential association of lymphocyte subsets with disease severity was further analyzed. Significantly decreased numbers of CD3+ and CD4+ T cells, and the CD4+/CD8+ ratio, but increased numbers of CD3−CD56+ NK and CD3+CD56+ NKT-like cells were observed in COPD patients compared to HNS. The frequencies of inducible IFN-γ-secreting NK and NKT-like cells were less in COPD patients. The frequencies of CD158a and CD158b on NK cells and CD158b on NKT-like cells were greater. The frequency of CD158b+ NK cells was negatively correlated with FEV1% prediction and FEV1/FVC. Our data indicate that COPD patients have immune dysfunction, and higher frequencies of inhibitory NK cells and NKT-like cells may participate in the pathogenesis of COPD.

  15. Lineage-Specific Effector Signatures of Invariant NKT Cells Are Shared amongst γδ T, Innate Lymphoid, and Th Cells.

    Science.gov (United States)

    Lee, You Jeong; Starrett, Gabriel J; Lee, Seungeun Thera; Yang, Rendong; Henzler, Christine M; Jameson, Stephen C; Hogquist, Kristin A

    2016-08-15

    Invariant NKT cells differentiate into three predominant effector lineages in the steady state. To understand these lineages, we sorted undifferentiated invariant NK T progenitor cells and each effector population and analyzed their transcriptional profiles by RNAseq. Bioinformatic comparisons were made to effector subsets among other lymphocytes, specifically Th cells, innate lymphoid cells (ILC), and γδ T cells. Myc-associated signature genes were enriched in NKT progenitors, like in other hematopoietic progenitors. Only NKT1 cells, but not NKT2 and NKT17 cells, had transcriptome similarity to NK cells and were also similar to other IFN-γ-producing lineages such as Th1, ILC1, and intraepithelial γδ T cells. NKT2 and NKT17 cells were similar to their analogous subsets of γδ T cells and ILCs, but surprisingly, not to Th2 and Th17 cells. We identified a set of genes common to each effector lineage regardless of Ag receptor specificity, suggesting the use of conserved regulatory cores for effector function. PMID:27385777

  16. Antitumor Immunity Produced by the Liver Kupffer Cells, NK Cells, NKT Cells, and CD8+ CD122+ T Cells

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    Shuhji Seki

    2011-01-01

    Full Text Available Mouse and human livers contain innate immune leukocytes, NK cells, NKT cells, and macrophage-lineage Kupffer cells. Various bacterial components, including Toll-like receptor (TLR ligands and an NKT cell ligand (α-galactocylceramide, activate liver Kupffer cells, which produce IL-1, IL-6, IL-12, and TNF. IL-12 activates hepatic NK cells and NKT cells to produce IFN-γ, which further activates hepatic T cells, in turn activating phagocytosis and cytokine production by Kupffer cells in a positive feedback loop. These immunological events are essentially evoked to protect the host from bacterial and viral infections; however, these events also contribute to antitumor and antimetastatic immunity in the liver by activated liver NK cells and NKT cells. Bystander CD8+CD122+ T cells, and tumor-specific memory CD8+T cells, are also induced in the liver by α-galactocylceramide. Furthermore, adoptive transfer experiments have revealed that activated liver lymphocytes may migrate to other organs to inhibit tumor growth, such as the lungs and kidneys. The immunological mechanism underlying the development of hepatocellular carcinoma in cirrhotic livers in hepatitis C patients and liver innate immunity as a double-edged sword (hepatocyte injury/regeneration, septic shock, autoimmune disease, etc. are also discussed.

  17. Increased cytotoxicity of CD4+ invariant NKT cells against CD4+CD25hiCD127lo/− regulatory T cells in allergic asthma

    OpenAIRE

    Nguyen, Khoa D.; Vanichsarn, Chris; Nadeau, Kari C.

    2008-01-01

    CD4+CD25hiCD127lo/− regulatory T cells (Treg) have been implicated in the resolution of asthma-associated inflammation while the opposite role of CD4+ invariant NKT (iNKT) cells has been the subject of recent investigations. Studies here focused on mechanisms of interaction between CD4+ iNKT cells and Treg to further explore their roles in allergic asthma (AA). Flow cytometry analysis revealed a significant increase in the expression of the natural cytotoxicity receptors NKp30 and NKp46 by CD...

  18. A case of rapid growing colonic NK/T cell lymphoma complicated by Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Shumei Zheng; Hui Xu; Qin Ouyang; Linyun Xue; Yong Zhang; Dejun Cui

    2013-01-01

    A 37-year-old man developed abdominal pain and bloody diarrhea 11 months before admission.The colonoscopy revealed multifocal ulcers in the colon.Histology showed active chronic inflammation.Although anti-tuberculosis medication was effective,his symptoms repeated 2 months later.The subsequent colonoscopy revealed more extensive irregular ulcers than before,and he was clinically suspected with intestinal malignant lymphoma.He underwent subtotal colectomy and was histologically suggested Crohn's disease,then 5-aminosalicylic and a combination of prednisone and azathioprine were administered in succession postoperatively,but they achieved minimal relief of symptoms for a period of 7 months.The third colonoscopy showed a large irregular ulcer in the ileocolon stomas,and primary colonic NK/T cell lymphoma was diagnosed through histological and immunophenotypic studies.Malignant lymphoma should be taken into consideration when clinically diagnosed Crohn's disease was refractory to medication or when its clinical course became aggressive.

  19. NKT cell stimulation with glycolipid antigen in vivo: co-stimulation-dependent expansion, Bim-dependent contraction, and hypo-responsiveness to further antigenic challenge1

    Science.gov (United States)

    Kyparissoudis, Konstantinos; Pellicci, Daniel G.; Zhan, Yifan; Lew, Andrew M.; Bouillet, Philippe; Strasser, Andreas; Smyth, Mark J.; Godfrey, Dale I.

    2005-01-01

    Activation of NKT cells using the glycolipid α-galactosylceramide (α-GalCer4) has availed many investigations into their immunoregulatory and therapeutic potential. However, it remains unclear how NKT cells respond to stimulation in vivo, which co-stimulatory pathways are important, and what factors (eg. antigen availability and activation-induced cell death) limit their response. We have explored these questions in the context of anin vivo model of NKT cell dynamics spanning activation, population expansion and subsequent contraction. Neither the B7/CD28 nor the CD40/CD40-L co-stimulatory pathways were necessary for cytokine production by activated NKT cells, either early (2 hours) or late (3 days) following initial stimulation, but both pathways were necessary for normal proliferative expansion of NKT cells in vivo. The pro-apoptotic Bcl-2 family member Bim was necessary for normal contraction of the NKT cell population between days 3-9 after stimulation, suggesting the pool size is regulated by apoptotic cell death in a manner similar to that of conventional T cells. Antigen availability was not the limiting factor for NKT cell expansion in vivo, and a second injection of α-GalCer induced a very blunted response, whereby cytokine production was reduced and further expansion did not occur. This appeared to be a form of anergy that was intrinsic to the NKT cells and not associated with up-regulation of inhibitory NK cell receptors such as NKG2A or Ly49 family members. Furthermore, NKT cells from mice pre-challenged with α-GalCer in vivoshowed little cytokine production and reduced proliferation in vitro. In summary, this study significantly enhances our understanding of how NKT cells respond to α-GalCer in vivo, revealing that the full primary response depends on costimulation via the CD28 and CD40 pathways, with subsequent Bim-dependent contraction. After contraction, the NKT cells are hypo-responsive to further antigenic induced expansion. PMID:16116198

  20. Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells

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    Shuichi Kitayama

    2016-02-01

    Full Text Available Vα24 invariant natural killer T (iNKT cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer. Conversely, reduced iNKT cell numbers and function have been observed in many patients with cancer. To recover these numbers, we reprogrammed human iNKT cells to pluripotency and then re-differentiated them into regenerated iNKT cells in vitro through an IL-7/IL-15-based optimized cytokine combination. The re-differentiated iNKT cells showed proliferation and IFN-γ production in response to α-galactosylceramide, induced dendritic cell maturation and downstream activation of both cytotoxic T lymphocytes and NK cells, and exhibited NKG2D- and DNAM-1-mediated NK cell-like cytotoxicity against cancer cell lines. The immunological features of re-differentiated iNKT cells and their unlimited availability from induced pluripotent stem cells offer a potentially effective immunotherapy against cancer.

  1. Pathogenic Role of NKT and NK Cells in Acetaminophen-Induced Liver Injury is Dependent on the Presence of DMSO

    OpenAIRE

    Masson, Mary Jane; Carpenter, Leah D.; Graf, Mary L.; Pohl, Lance R.

    2008-01-01

    Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. While DMSO is generally thought of as being relatively inert, it can induce biological effects that are often overlooked. An example highlighting this potential problem is found in the recent report demonstrating a pathogenic role for NKT and NK cells in acetaminophen-induced liver injury (AILI) in C57Bl/6 mice in which DMSO was used to facilitate APAP dissolution. We ...

  2. Opposing Effects of Prednisolone Treatment on T/NKT Cell- and Hepatotoxin-mediated Hepatitis in Mice

    OpenAIRE

    Kwon, Hyo-Jung; Won, Young-Suk; Park, Ogyi; Feng, Dechun; Gao, Bin

    2014-01-01

    Prednisolone is a corticosteroid that has been used to treat inflammatory liver diseases, such as autoimmune hepatitis and alcoholic hepatitis. However, the results have been controversial, and how prednisolone affects liver disease progression remains unknown. In the current study, we examined the effect of prednisolone treatment on several models of liver injury, including T/NKT cell hepatitis induced by concanavalin A (ConA) and α-galactosylceramide (α-GalCer), and hepatotoxin-mediated hep...

  3. NK and NKT Cell Depletion Alters the Outcome of Experimental Pneumococcal Pneumonia: Relationship with Regulation of Interferon-γ Production

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    Eirini Christaki

    2015-01-01

    Full Text Available Background. Natural killer (NK and natural killer T (NKT cells contribute to the innate host defense but their role in bacterial sepsis remains controversial. Methods. C57BL/6 mice were infected intratracheally with 5 × 105 cfu of Streptococcus pneumoniae. Animals were divided into sham group (Sham; pretreated with isotype control antibody (CON group; pretreated with anti-asialo GM1 antibody (NKd group; and pretreated with anti-CD1d monoclonal antibody (NKTd group before bacterial challenge. Serum and tissue samples were analyzed for bacterial load, cytokine levels, splenocyte apoptosis rates, and cell characteristics by flow cytometry. Splenocyte miRNA expression was also analyzed and survival was assessed. Results. NK cell depletion prolonged survival. Upon inhibition of NKT cell activation, spleen NK (CD3−/NK1.1+ cells increased compared to all other groups. Inhibition of NKT cell activation led to higher bacterial loads and increased levels of serum and splenocyte IFN-γ. Splenocyte miRNA analysis showed that miR-200c and miR-29a were downregulated, while miR-125a-5p was upregulated, in anti-CD1d treated animals. These changes were moderate after NK cell depletion. Conclusions. NK cells appear to contribute to mortality in pneumococcal pneumonia. Inhibition of NKT cell activation resulted in an increase in spleen NK (CD3−/NK1.1+ cells and a higher IFN-γ production, while altering splenocyte miRNA expression.

  4. CRISPR-Mediated Triple Knockout of SLAMF1, SLAMF5 and SLAMF6 Supports Positive Signaling Roles in NKT Cell Development

    Science.gov (United States)

    Huang, Bonnie; Gomez-Rodriguez, Julio; Preite, Silvia; Garrett, Lisa J.; Harper, Ursula L.; Schwartzberg, Pamela L.

    2016-01-01

    The SLAM family receptors contribute to diverse aspects of lymphocyte biology and signal via the small adaptor molecule SAP. Mutations affecting SAP lead to X-linked lymphoproliferative syndrome Type 1, a severe immunodysregulation characterized by fulminant mononucleosis, dysgammaglobulinemia, and lymphoproliferation/lymphomas. Patients and mice having mutations affecting SAP also lack germinal centers due to a defect in T:B cell interactions and are devoid of invariant NKT (iNKT) cells. However, which and how SLAM family members contribute to these phenotypes remains uncertain. Three SLAM family members: SLAMF1, SLAMF5 and SLAMF6, are highly expressed on T follicular helper cells and germinal center B cells. SLAMF1 and SLAMF6 are also implicated in iNKT development. Although individual receptor knockout mice have limited iNKT and germinal center phenotypes compared to SAP knockout mice, the generation of multi-receptor knockout mice has been challenging, due to the genomic linkage of the genes encoding SLAM family members. Here, we used Cas9/CRISPR-based mutagenesis to generate mutations simultaneously in Slamf1, Slamf5 and Slamf6. Genetic disruption of all three receptors in triple-knockout mice (TKO) did not grossly affect conventional T or B cell development and led to mild defects in germinal center formation post-immunization. However, the TKO worsened defects in iNKT cells development seen in SLAMF6 single gene-targeted mice, supporting data on positive signaling and potential redundancy between these receptors. PMID:27258160

  5. Blockade of IL-33 ameliorates Con A-induced hepatic injury by reducing NKT cell activation and IFN-γ production in mice.

    Science.gov (United States)

    Chen, Jie; Duan, Lihua; Xiong, Ali; Zhang, Hongwei; Zheng, Fang; Tan, Zheng; Gong, Feili; Fang, Min

    2012-12-01

    IL-33, a recently described member of the IL-1 family, has been identified as a cytokine endowed with pro-Th2 type functions. To date, there are only limited data on its role in physiological and pathological hepatic immune responses. In this study, we examined the role of IL-33 in immune-mediated liver injury by exploring the model of concanavalin A (Con A)-induced hepatitis. We observed that the level of IL-33 expression in the liver was dramatically increased at 12 h after Con A injection. Meanwhile, ST2L, the receptor of IL-33, was significantly up-regulated in lymphocytes including T and natural killer T (NKT) cells, especially in NKT cells. Moreover, administration of recombinant IL-33 exacerbated Con A-induced hepatitis, while pretreatment of IL-33-blocking antibody or psST2-Fc plasmids showed a protective effect probably by inhibiting the activation of late stage of T cells and NKT cells and also decreasing the production of the cytokine IFN-γ. Furthermore, depletion of NKT cells abolished the protective effect of IL-33-blocking antibody, and IL-33 failed to exacerbate Con A-induced hepatitis in IFN-γ(-/-) mice. These data suggested the critical roles of NKT cells and IFN-γ in the involvement of IL-33 in Con A-induced hepatitis. Blockade of IL-33 may represent a novel therapeutic strategy through IL-33/ST2L signal to prevent immune-mediated liver injury.

  6. Vγ4 γδ T cell-derived IL-17A negatively regulates NKT cell function in Con A-induced fulminant hepatitis.

    Science.gov (United States)

    Zhao, Na; Hao, Jianlei; Ni, Yuanyuan; Luo, Wei; Liang, Ruifang; Cao, Guangchao; Zhao, Yapu; Wang, Puyue; Zhao, Liqing; Tian, Zhigang; Flavell, Richard; Hong, Zhangyong; Han, Jihong; Yao, Zhi; Wu, Zhenzhou; Yin, Zhinan

    2011-11-15

    Con A-induced fulminant hepatitis is a well-known animal model for acute liver failure. However, the role of γδ T cells in this model is undefined. In this report, using TCR δ(-/-) mice, we demonstrated a protective role of γδ T cells in Con A-induced hepatitis model. TCR δ(-/-) mice showed significantly decreased levels of IL-17A and IL-17F in the Con A-treated liver tissue, and reconstitution of TCR δ(-/-) mice with wild-type (Wt), but not IL-17A(-/-), γδ T cells significantly reduced hepatitis, strongly suggesting a critical role of IL-17A in mediating the protective effect of γδ T cells. Interestingly, only Vγ4, but not Vγ1, γδ T cells exerted such a protective effect. Furthermore, depletion of NKT cells in TCR δ(-/-) mice completely abolished hepatitis, and NKT cells from Con A-challenged liver tissues of TCR δ(-/-) mice expressed significantly higher amounts of proinflammatory cytokine IFN-γ than those from Wt mice, indicating that γδ T cells protected hepatitis through targeting NKT cells. Finally, abnormal capacity of IFN-γ production by NKT cells of TCR δ(-/-) mice could only be downregulated by transferring Wt, but not IL-17(-/-), Vγ4 γδ T cells, confirming an essential role of Vγ4-derived IL-17A in regulating the function of NKT cells. In summary, our report thus demonstrated a novel function of Vγ4 γδ T cells in mediating a protective effect against Con A-induced fulminant hepatitis through negatively regulating function of NKT cells in an IL-17A-dependent manner, and transferring Vγ4 γδ T cells may provide a novel therapeutic approach for this devastating liver disease.

  7. Modulation of NKT cells and Th1/Th2 imbalance after α-GalCer treatment in progressive load-trained rats

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    Wang Ru, Chen Peijie

    2009-01-01

    Full Text Available Purpose: The purpose of this study was to determine whether α-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, can ameliorate exercise-induced immune imbalance. Methods: Eight-week-old female Sprague-Dawley rats were trained with a progressively increasing load for 9 weeks. At 36 h and at 7 d after training, groups of rats were euthanized. The whole blood was used to detect hemoglobin(Hb, plasma was analyzed for hormones testosterone(T and corticosterone(C, and spleen was harvested for detecting NKT cells and interferon-γ (IFN-γ and interleukin (IL-4 producing cells. Results: Two-way analysis of variance (ANOVA showed significant differences between training and time in Series 1. The results showed, at 36h after training, that the decrease in Hb, T and C concentration reflected overtraining or excessive exercise. At 7 d after training, NKT cell populations decreased, and a T helper 1/T helper 2 (Th1/Th2 lymphocyte imbalance occurred. In Series 2, α-galactosylceramide (α-GalCer, an NKT cell activator was found to enhance NKT cell numbers by 69% and shift the Th1/Th2 lymphocyte imbalance by observably decreaseing the frequency of IL-4 secreting cells. Conclusion: These data showed that, in addition to Th1/Th2 self-regulation, α-GalCer played an important modulatory role in the exercise-induced Th1/Th2 lymphocyte imbalance, which may be correlative with NKT immunoregulatory cells.

  8. Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice.

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    Karsten Buschard

    Full Text Available BACKGROUND: Ethanol ('alcohol' is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules. METHODS: The study included cellular in vitro tests using α-galactosylceramide (αGalCer, and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses. RESULTS: Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05. CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05, whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms. CONCLUSION: Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases.

  9. Lymphomatoidgastropathy mimicking extranodal NK/T cell lymphoma, nasal type: A case report

    Institute of Scientific and Technical Information of China (English)

    Tomohiro Terai; Mitsushige Sugimoto; Hiroki Uozaki; Tetsushi Kitagawa; Mana Kinoshita; Satoshi Baba; Takanori Yamada; Satoshi Osawa; Ken Sugimoto

    2012-01-01

    Extranodal natural killer (NK)/T-cell lymphoma,nasal type,exhibits aggressive tumor behavior and carries a poor prognosis.Recently,lymphomatoid gastropathy with NK/T cell infiltration into gastric mucosa has been recognized as a pseudo-malignant disease which regresses without treatment.Because the conventional immunohistochemical criteria of lymphomatoid gastropathy is similar to that of extranodal NK/T-cell lymphoma nasal type,it is difficult to distinguish between the two conditions by histopathological evaluation only.Here,we report a rare case of lymphomatoid gastropathy in a 57-year-old female.Gastroendoscopy on routine check-up revealed elevated reddish lesions < 1 cm in diameter in the gastric fornix and body.Although repeat endoscopies at 1 and 6 mo later revealed no gastric lesions at any locations without any treatments,at 12 mo later gastric lymphomatoid lesions recurred at gastric fornix and body.Histological examination of endoscopic biopsy specimens at 12 mo showed atypical NK cell infiltration with CD3+,CD4-,CD5-,CD7+,CD8-,CD20-,CD30-,CD56+,CD79a-and T-cell-restricted intracellular antigen-1+ into gastric mucosa.After treatment for Helicobacter pylori (H.pylori) eradication,the lesions disappeared in all locations of the gastric fornix and body over the subsequent 12 mo.Here,we report a case of H.pylori-positive lymphomatoid gastropathy with massive NK-cell proliferation,and also review the literature concerning newly identified lymphomatoid gastropathy based on comparison of extra nodal NK/T-cell lymphoma nasal type.In any case,these lesions are evaluated with biopsy specimens,the possibility of this benign entity should be considered,and excessive treatment should be carefully avoided.Close follow-up for this case of lymphomatoid gastropathy is necessary to exclude any underlying malignancy.

  10. IL-12 and IL-18 Induction and Subsequent NKT Activation Effects of the Japanese Botanical Medicine Juzentaihoto

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    Ken Taniguchi

    2008-07-01

    Full Text Available In this study, we first measured some cytokine concentrations in the serum of patients treated with Juzentaihoto (JTT. Of the cytokines measured interleukin (IL -18 was the most prominently up-regulated cytokine in the serum of patients under long term JTT administration. We next evaluated the effects of JTT in mice, focusing especially on natural killer T (NKT cell induction. Mice fed JTT were compared to control group ones. After sacrifice, the liver was fixed, embedded and stained. Transmission electron microscope (TEM observations were performed. Although the mice receiving the herbal medicine had same appearance, their livers were infiltrated with massive mononuclear cells, some of which were aggregated to form clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of IL-12 and IL-18 in the liver of JTT treated mice. To clarify what the key molecules that induce immunological restoration with JTT might be, we next examined in vitro lymphocyte cultures. Mononuclear cells isolated and prepared from healthy volunteers were cultured with and without JTT. Within 24 hours, JTT induced the IL-12 and IL-18 production and later (72 hours induction of interferon (IFN-gamma. Oral administration of JTT may induce the expression of IL-12 in the early stage, and IL-18 in the chronic stage, followed by NKT induction. Their activation, following immunological restoration could contribute to anti-tumor effects.

  11. Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant

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    Shailbala Singh

    2014-10-01

    Full Text Available Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.

  12. NK/T细胞淋巴瘤细胞凋亡和细胞增殖特征及意义%The significance and features of apoptosis and proliferation of NK/T cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    Dabin Wang; Meng Ming; Junhua Liu; Jianhua Yi; Dianding Zou

    2011-01-01

    Objective:The aim was to study the features and clinical significance of cell apoptosis and proliferation of NK/T cell lymphoma. Methods:TdT-mediated dUTP nick end labeling and immunohistochemical Streptavidin-peroxidase method were used to study cell apoptosis and the expression of proliferation cell nuclear antigen in 25 NK/T cell lymphoma and 10reactive lymphoid tissues. Results:Apoptotic index (AI) and proliferative index (PI) averaged (1.92% ± 0.86%) and (41.48%± 5.10%) respectively in the 25 NK/T cell lymphomas and (6.70% ± 1.89%) and (20.10% ± 2.77%) in the 10 reactive lymphoid tissues. Compared with reactive lymphoid tissues, AI was significantly reduced in NK/T cell lymphoma (t = 10.80, P < 0.01)while PI significantly increased (t = 12.39, P < 0.01). In addition, in NK/T cell lymphoma, AI and PI were positively related (r = 0.69, P < 0.01). Conclusion:In NK/T cell lymphoma, cell apoptosis is reduced while cell proliferation increased. The imbalance between cell apoptosis and cell proliferation is closely related to the development and progression of NK/T cell lymphoma.

  13. Subpopulations, phenotypes and biological characterization of human NKT cells in PBMCs%人外周血NKT细胞亚群表型及生物学特征

    Institute of Scientific and Technical Information of China (English)

    李子涛; 杨滨燕; 吴长有

    2011-01-01

    目的:观察正常人周围血NKT细胞的频率、表型特征及功能,进一步了解NKT细胞在免疫应答中的作用.方法:分离正常成年人PBMCs,利用流式细胞术(FCM)检测TCRvβ11、CD4、CD8、 CD45RA、CD62L、CCR7等表面分子的表达;PMA+Ionomycin刺激PBMCs后,检测细胞因子的产生.结果:正常成年人周围血CD3+TCRvβ11+NKT细胞的平均频率为0.35%,其范围为0.11%~1.20%.根据CD4和CD8分子的表达,可将CD3+TCRvβ11+NKT细胞分为CD4+、CD8+、CD4-CD8-三个亚群,分别为56.24%、25.82%、16.47%.此外多数CD3+TCRvβ11+NKT细胞表达CD45RA,近半数细胞表达CD62L,少数细胞表达CCR7.细胞因子表达的结果显示,经PMA和Ionomycin刺激后,近30%的CD3+TCRvβ11+NKT细胞分泌IFN-γ,6.9%的细胞分泌IL-4.CD4+NKT细胞产生IL-4的量要明显高于CD8+NKT细胞,但IFN-γ的表达二者没有明显差别.重要的是初始和记忆性NKT细胞都能产生细胞因子,以记忆性NKT细胞为主.结论:正常人周围血中CD3+TCRvβ11+NKT细胞的频率很小,但其表型复杂,产生细胞因子IFN-γ和IL-4的频率高,参与免疫调节及免疫应答的过程.%Objective: To characterize NKT cells in PBMCs from normal human adult donors. Methods: PBMCs from blood donors were isolated and cell surface markers (CD3,TCRvβll,CD4,CD8,CD45RA,CD62L and CCR7) and intracellular cytokines (IL-4 and IFN-γ) were detected by flow cytometry directly or after stimulation with PMA plus Ionomycin. Results:The average frequency of CD3+ TCRvβ11 + NKT cells from blood donors was 0.35 % and varied from 0.11% to 1.20%. Three distinct subpopulations ( CD4 + NKT 56.24%, CD8 + NKT 25.83 %andCD4-CD88-NKT 16.47%) of human CD3+ TCRvβll+ NKT cells could be identified based upon the expression of CD4 and CD8 molecules. Most of the CD3+ TCRvβ11 + NKT cells expressed CD45RA,and about half of them expressed CD62L while a few of them expressed CCR7. After the stimulation by PMA plus Ionomycin,about 30% of CD3

  14. Identification of distinct human invariant natural killer T-cell response phenotypes to alpha-galactosylceramide

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    Besra Gurdyal S

    2008-12-01

    Full Text Available Abstract Background Human CD1d-restricted, invariant natural killer T cells (iNKT are a unique class of T lymphocytes that recognise glycolipid antigens such as α-galactosylceramide (αGalCer and upon T cell receptor (TCR activation produce both Th1 and Th2 cytokines. iNKT cells expand when cultured in-vitro with αGalCer and interleukin 2 (IL-2 in a CD1d-restricted manner. However, the expansion ratio of human iNKT cells varies between individuals and this has implications for attempts to manipulate this pathway therapeutically. We have studied a panel of twenty five healthy human donors to assess the variability in their in-vitro iNKT cell expansion responses to stimulation with CD1d ligands and investigated some of the factors that may influence this phenomenon. Results Although all donors had comparable numbers of circulating iNKT cells their growth rates in-vitro over 14 days in response to a range of CD1d ligands and IL-2 were highly donor-dependent. Two reproducible donor response patterns of iNKT expansion were seen which we have called 'strong' or 'poor' iNKT responders. Donor response phenotype did not correlate with age, gender, frequency of circulating iNKT, or with the CD1d ligand utilised. Addition of exogenous recombinant human interleukin 4 (IL-4 to 'poor' responder donor cultures significantly increased their iNKT proliferative capacity, but not to levels equivalent to that of 'strong' responder donors. However in 'strong' responder donors, addition of IL-4 to their cultures did not significantly alter the frequency of iNKT cells in the expanded CD3+ population. Conclusion (i in-vitro expansion of human iNKT cells in response to CD1d ligand activation is highly donor variable, (ii two reproducible patterns of donor iNKT expansion were observed, which could be classified into 'strong' and 'poor' responder phenotypes, (iii donor iNKT response phenotypes did not correlate with age, gender, frequency of circulating iNKT cells, or

  15. iNKT Cells Are Responsible for the Apoptotic Reduction of Basophils That Mediate Th2 Immune Responses Elicited by Papain in Mice Following γPGA Stimulation.

    Science.gov (United States)

    Park, Hyun Jung; Lee, Sung Won; Park, Se-Ho; Hong, Seokmann

    2016-01-01

    Recent studies have demonstrated that Bacillus subtilis-derived poly-gamma glutamic acid (γPGA) treatment suppresses the development of allergic diseases such as atopic dermatitis (AD). Although basophils, an innate immune cell, are known to play critical roles in allergic immune responses and repeated long-term administration of γPGA results in decreased splenic basophils in an AD murine model, the underlying mechanisms by which γPGA regulates basophil frequency remain unclear. To investigate how γPGA modulates basophils, we employed basophil-mediated Th2 induction in vivo model elicited by the allergen papain protease. Repeated injection of γPGA reduced the abundance of basophils and their production of IL4 in mice, consistent with our previous study using NC/Nga AD model mice. The depletion of basophils by a single injection of γPGA was dependent on the TLR4/DC/IL12 axis. CD1d-dependent Vα14 TCR invariant natural killer T (iNKT) cells are known to regulate a variety of immune responses, such as allergy. Because iNKT cell activation is highly sensitive to IL12 produced by DCs, we evaluated whether the effect of γPGA on basophils is mediated by iNKT cell activation. We found that in vivo γPGA treatment did not induce the reduction of basophils in iNKT cell-deficient CD1d KO mice, suggesting the critical role of iNKT cells in γPGA-mediated basophil depletion at the early time points. Furthermore, increased apoptotic basophil reduction triggered by iNKT cells upon γPGA stimulation was mainly attributed to Th1 cytokines such as IFNγ and TNFα, consequently resulting in inhibition of papain-induced Th2 differentiation via diminishing basophil-derived IL4. Taken together, our results clearly demonstrate that γPGA-induced iNKT cell polarization toward the Th1 phenotype induces apoptotic basophil depletion, leading to the suppression of Th2 immune responses. Thus, elucidation of the crosstalk between innate immune cells will contribute to the design and

  16. A prognostic model based on pretreatment platelet lymphocyte ratio for stage IE/IIE upper aerodigestive tract extranodal NK/T cell lymphoma, nasal type.

    Science.gov (United States)

    Wang, Ke-feng; Chang, Bo-yang; Chen, Xiao-qin; Liu, Pan-pan; Wuxiao, Zhi-jun; Wang, Zhi-hui; Li, Su; Jiang, Wen-qi; Xia, Zhong-jun

    2014-12-01

    Patients with stage IE/IIE natural killer T (NK/T) cell lymphomas have discrepant survival outcome. This study aims to establish a prognostic model based on the pretreatment platelet lymphocyte ratio (PLR) specifically for localized extranodal NK/T cell lymphoma to guide the therapy. We retrospectively analyzed the data of 252 patients with early-stage upper aerodigestive tract NK/T cell lymphoma. The 5-year overall survival rate in 252 patients was 67.1%. Prognostic factors for survival were female (P = 0.025; relative risk, 0.51; 95% CI 0.28-0.92), older age (P = 0.000; relative risk, 3.34; 95% CI 1.94-5.75), stage II(P = 0.020; relative risk, 1.79; 95% CI 1.10-2.91), lactate dehydrogenase (LDH) level (P = 0.009; relative risk, 2.00; 95% CI 1.19-3.35), and PLR (P = 0.020; relative risk, 1.77; 95% CI 1.10-2.87). Based on these five parameters, we identified three different risk groups: group 1(106 cases, 43.4%), no or one adverse factor; group 2(85 cases, 34.8%), two factors; group 3(53 cases, 21.7%), three to five factors. Five-year overall survival was 83.3% for group 1, 62.2% for group 2, and 43.1% for group 3 (P = 0.000). Compared with International Prognostic Index and Korean Prognostic Index, the new model has a better prognostic discrimination for the patients of stage IE/IIE upper aerodigestive tract NK/T cell lymphoma. The PLR-based prognosis model is useful to stratify patients with localized extranodal NK/T cell lymphoma into different risk groups and guide the treatment modalities selection. PMID:25377661

  17. Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs.

    Science.gov (United States)

    Dwivedi, Varun; Manickam, Cordelia; Dhakal, Santosh; Binjawadagi, Basavaraj; Ouyang, Kang; Hiremath, Jagadish; Khatri, Mahesh; Hague, Jacquelyn Gervay; Lee, Chang Won; Renukaradhya, Gourapura J

    2016-04-15

    Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of induction of strong local mucosal immunity in the respiratory tract. Invariant natural killer T (iNKT) cell is a unique T cell subset, and activation of iNKT cell using its ligand α-Galactosylceramide (α-GalCer) has been shown to potentiate the cross-protective immunity to inactivated influenza virus vaccine candidates in mice. Recently, we discovered iNKT cell in pig and demonstrated its activation using α-GalCer. In this study, we evaluated the efficacy of an inactivated H1N1 SwIV coadministered with α-GalCer intranasally against a homologous viral challenge. Our results demonstrated the potent adjuvant effects of α-GalCer in potentiating both innate and adaptive immune responses to SwIV Ags in the lungs of pigs, which resulted in reduction in the lung viral load by 3 logs compared to without adjuvant. Immunologically, in the lungs of pigs vaccinated with α-GalCer an increased virus specific IgA response, IFN-α secretion and NK cell-cytotoxicity was observed. In addition, iNKT cell-stimulation enhanced the secretion of Th1 cytokines (IFN-γ and IL-12) and reduced the production of immunosuppressive cytokines (IL-10 and TGF-β) in the lungs of pigs⋅ In conclusion, we demonstrated for the first time iNKT cell adjuvant effects in pigs to SwIV Ags through augmenting the innate and adaptive immune responses in the respiratory tract.

  18. Group 2 innate lymphoid cell production of IL-5 is regulated by NKT cells during influenza virus infection.

    Directory of Open Access Journals (Sweden)

    Stacey Ann Gorski

    2013-09-01

    Full Text Available Respiratory virus infections, such as influenza, typically induce a robust type I (pro-inflammatory cytokine immune response, however, the production of type 2 cytokines has been observed. Type 2 cytokine production during respiratory virus infection is linked to asthma exacerbation; however, type 2 cytokines may also be tissue protective. Interleukin (IL-5 is a prototypical type 2 cytokine that is essential for eosinophil maturation and egress out of the bone marrow. However, little is known about the cellular source and underlying cellular and molecular basis for the regulation of IL-5 production during respiratory virus infection. Using a mouse model of influenza virus infection, we found a robust transient release of IL-5 into infected airways along with a significant and progressive accumulation of eosinophils into the lungs, particularly during the recovery phase of infection, i.e. following virus clearance. The cellular source of the IL-5 was group 2 innate lymphoid cells (ILC2 infiltrating the infected lungs. Interestingly, the progressive accumulation of eosinophils following virus clearance is reflected in the rapid expansion of c-kit⁺ IL-5 producing ILC2. We further demonstrate that the enhanced capacity for IL-5 production by ILC2 during recovery is concomitant with the enhanced expression of the IL-33 receptor subunit, ST2, by ILC2. Lastly, we show that NKT cells, as well as alveolar macrophages (AM, are endogenous sources of IL-33 that enhance IL-5 production from ILC2. Collectively, these results reveal that c-kit⁺ ILC2 interaction with IL-33 producing NKT and AM leads to abundant production of IL-5 by ILC2 and accounts for the accumulation of eosinophils observed during the recovery phase of influenza infection.

  19. Exploiting the role of endogenous lymphoid-resident dendritic cells in the priming of NKT cells and CD8+ T cells to dendritic cell-based vaccines.

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    Troels R Petersen

    Full Text Available Transfer of antigen between antigen-presenting cells (APCs is potentially a physiologically relevant mechanism to spread antigen to cells with specialized stimulatory functions. Here we show that specific CD8+ T cell responses induced in response to intravenous administration of antigen-loaded bone marrow-derived dendritic cells (BM-DCs, were ablated in mice selectively depleted of endogenous lymphoid-resident langerin+ CD8α+ dendritic cells (DCs, suggesting that the antigen is transferred from the injected cells to resident APCs. In contrast, antigen-specific CD4+ T cells were primed predominantly by the injected BM-DCs, with only very weak contribution of resident APCs. Crucially, resident langerin+ CD8α+ DCs only contributed to the priming of CD8+ T cells in the presence of maturation stimuli such as intravenous injection of TLR ligands, or by loading the BM-DCs with the glycolipid α-galactosylceramide (α-GalCer to recruit the adjuvant activity of activated invariant natural killer-like T (iNKT cells. In fact, injection of α-GalCer-loaded CD1d-/- BM-DCs resulted in potent iNKT cell activation, suggesting that this glycolipid antigen can also be transferred to resident CD1d+ APCs. While iNKT cell activation per se was independent of langerin+ CD8α+ DCs, some iNKT cell-mediated activities were reduced, notably release of IL-12p70 and transactivation of NK cells. We conclude that both protein and glycolipid antigens can be exchanged between distinct DC species. These data suggest that the efficacy of DC-based vaccination strategies may be improved by the incorporation of a systemic maturation signal aimed to engage resident APCs in CD8+ T cell priming, and α-GalCer may be particularly well suited to this purpose.

  20. Humans lack iGb3 due to the absence of functional iGb3-synthase: implications for NKT cell development and transplantation.

    Directory of Open Access Journals (Sweden)

    Dale Christiansen

    2008-07-01

    Full Text Available The glycosphingolipid isoglobotrihexosylceramide, or isogloboside 3 (iGb3, is believed to be critical for natural killer T (NKT cell development and self-recognition in mice and humans. Furthermore, iGb3 may represent an important obstacle in xenotransplantation, in which this lipid represents the only other form of the major xenoepitope Galalpha(1,3Gal. The role of iGb3 in NKT cell development is controversial, particularly with one study that suggested that NKT cell development is normal in mice that were rendered deficient for the enzyme iGb3 synthase (iGb3S. We demonstrate that spliced iGb3S mRNA was not detected after extensive analysis of human tissues, and furthermore, the iGb3S gene contains several mutations that render this product nonfunctional. We directly tested the potential functional activity of human iGb3S by expressing chimeric molecules containing the catalytic domain of human iGb3S. These hybrid molecules were unable to synthesize iGb3, due to at least one amino acid substitution. We also demonstrate that purified normal human anti-Gal immunoglobulin G can bind iGb3 lipid and mediate complement lysis of transfected human cells expressing iGb3. Collectively, our data suggest that iGb3S is not expressed in humans, and even if it were expressed, this enzyme would be inactive. Consequently, iGb3 is unlikely to represent a primary natural ligand for NKT cells in humans. Furthermore, the absence of iGb3 in humans implies that it is another source of foreign Galalpha(1,3Gal xenoantigen, with obvious significance in the field of xenotransplantation.

  1. Preventing and curing citrulline-induced autoimmune arthritis in a humanized mouse model using a Th2-polarizing iNKT cell agonist.

    Science.gov (United States)

    Walker, Kyle M; Rytelewski, Mateusz; Mazzuca, Delfina M; Meilleur, Shannon A; Mannik, Lisa A; Yue, David; Brintnell, William C; Welch, Ian; Cairns, Ewa; Haeryfar, S M Mansour

    2012-07-01

    Invariant natural killer T (iNKT) cells are innate lymphocytes with unique reactivity to glycolipid antigens bound to non-polymorphic CD1d molecules. They are capable of rapidly releasing pro- and/or anti-inflammatory cytokines and constitute attractive targets for immunotherapy of a wide range of diseases including autoimmune disorders. In this study, we have explored the beneficial effects of OCH, a Th2-polarizing glycolipid agonist of iNKT cells, in a humanized mouse model of rheumatoid arthritis (RA) in which citrullinated human proteins are targeted by autoaggressive immune responses in mice expressing an RA susceptibility human leukocyte antigen (HLA) DR4 molecule. We found for the first time that treatment with OCH both prevents and cures citrulline-induced autoimmune arthritis as evidenced by resolved ankle swelling and reversed histopathological changes associated with arthritis. Also importantly, OCH treatment blocked the arthritogenic capacity of citrullinated antigen-experienced splenocytes without compromising their global responsiveness or altering the proportion of splenic naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T cells. Interestingly, administering the Th1-promoting iNKT cell glycolipid ligand α-C-galactosylceramide into HLA-DR4 transgenic mice increased the incidence of arthritis in these animals and exacerbated their clinical symptoms, strongly suggesting a role for Th1 responses in the pathogenesis of citrulline-induced arthritis. Therefore, our findings indicate a role for Th1-mediated immunopathology in citrulline-induced arthritis and provide the first evidence that iNKT cell manipulation by Th2-skewing glycolipids may be of therapeutic value in this clinically relevant model, a finding that is potentially translatable to human RA. PMID:21912419

  2. IL-10 Production Is Critical for Sustaining the Expansion of CD5+ B and NKT Cells and Restraining Autoantibody Production in Congenic Lupus-Prone Mice.

    Science.gov (United States)

    Baglaenko, Yuriy; Manion, Kieran P; Chang, Nan-Hua; Gracey, Eric; Loh, Christina; Wither, Joan E

    2016-01-01

    The development and progression of systemic lupus erythematosus is mediated by the complex interaction of genetic and environmental factors. To decipher the genetics that contribute to pathogenesis and the production of pathogenic autoantibodies, our lab has focused on the generation of congenic lupus-prone mice derived from the New Zealand Black (NZB) strain. Previous work has shown that an NZB-derived chromosome 4 interval spanning 32 to 151 Mb led to expansion of CD5+ B and Natural Killer T (NKT) cells, and could suppress autoimmunity when crossed with a lupus-prone mouse strain. Subsequently, it was shown that CD5+ B cells but not NKT cells derived from these mice could suppress the development of pro-inflammatory T cells. In this paper, we aimed to further resolve the genetics that leads to expansion of these two innate-like populations through the creation of additional sub-congenic mice and to characterize the role of IL-10 in the suppression of autoimmunity through the generation of IL-10 knockout mice. We show that expansion of CD5+ B cells and NKT cells localizes to a chromosome 4 interval spanning 91 to 123 Mb, which is distinct from the region that mediates the majority of the suppressive phenotype. We also demonstrate that IL-10 is critical to restraining autoantibody production and surprisingly plays a vital role in supporting the expansion of innate-like populations. PMID:26964093

  3. TLR3 signaling in macrophages is indispensable for the protective immunity of invariant natural killer T cells against enterovirus 71 infection.

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    Kai Zhu

    2015-01-01

    Full Text Available Enterovirus 71 (EV71 is the most virulent pathogen among enteroviruses that cause hand, foot and mouth disease in children but rarely in adults. The mechanisms that determine the age-dependent susceptibility remain largely unclear. Here, we found that the paucity of invariant natural killer T (iNKT cells together with immaturity of the immune system was related to the susceptibility of neonatal mice to EV71 infection. iNKT cells were crucial antiviral effector cells to protect young mice from EV71 infection before their adaptive immune systems were fully mature. EV71 infection led to activation of iNKT cells depending on signaling through TLR3 but not other TLRs. Surprisingly, iNKT cell activation during EV71 infection required TLR3 signaling in macrophages, but not in dendritic cells (DCs. Mechanistically, interleukin (IL-12 and endogenous CD1d-restricted antigens were both required for full activation of iNKT cells. Furthermore, CD1d-deficiency led to dramatically increased viral loads in central nervous system and more severe disease in EV71-infected mice. Altogether, our results suggest that iNKT cells may be involved in controlling EV71 infection in children when their adaptive immune systems are not fully developed, and also imply that iNKT cells might be an intervention target for treating EV71-infected patients.

  4. Dynamic changes of cytotoxic T lymphocytes (CTLs, natural killer (NK cells, and natural killer T (NKT cells in patients with acute hepatitis B infection

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    Liu Bo

    2011-05-01

    Full Text Available Abstract Background The goal of this study is to observe changes in HBcAg-specific cytotoxic T lymphocytes (CTLs, natural killer (NK and natural killer T (NKT cells from peripheral blood and to relate such changes on viral clearance and liver injury in patients with acute hepatitis B (AHB. Methods Dynamic profiles on the frequency of HLA-A0201-restricted HBcAg18-27 pentamer complex (MHC-Pentamer-specific CTLs and lymphocyte subsets in AHB patients were analyzed in addition to liver function tests, HBV serological markers, and HBV DNA levels. ELISPOT was used to detect interferon-gamma (INF-γ secretion in specific CTLs stimulated with known T cell epitope peptides associated with HBV surface protein, polymerase, and core protein. Results HBV-specific CTL frequencies in AHB patients were much higher than in patients with chronic hepatitis B (CHB (p +CD8+ T cell numbers in AHB patients was more than observed in the healthy control group from the first to the fourth week after admission (p = 0.008 and 0.01, respectively; the number of CD3+CD8+ T cells and frequency of HBcAg18-27-specific CTLs in AHB patients reached peak levels at the second week after admission. NK and NKT cell numbers were negatively correlated with the frequency of HBcAg-specific CTLs (r = -0.266, p = 0.05. Conclusions Patients with AHB possess a higher frequency of HBcAg-specific CTLs than CHB patients. The frequency of specific CTLs in AHB patients is correlated with HBeAg clearance indicating that HBV-specific CTLs play an important role in viral clearance and the self-limited process of the disease. Furthermore, NK and NKT cells are likely involved in the early, non-specific immune response to clear the virus.

  5. Pollution of mycological surfaces in hospital emergency departments correlates positively with blood NKT CD3(+) 16(+) 56(+) and negatively with CD4(+) cell levels of their staff.

    Science.gov (United States)

    Suska, Milena; Lewicki, Sławomir; Kiepura, Anna; Winnicka, Izabela; Leszczyński, Paweł; Bielawska-Drózd, Agata; Cieślik, Piotr; Kubiak, Leszek; Depczyńska, Daria; Brewczyńska, Aleksandra; Skopińska-Różewska, Ewa; Kocik, Janusz

    2016-01-01

    The aim of the present study was the assessment of the putative influence of yeast and filamentous fungi in healthcare and control (office) workplaces (10 of each kind) on immune system competence measured by NK (natural killer), CD4(+), and NKT (natural killer T lymphocyte) cell levels in the blood of the personnel employed at these workplaces. Imprints from floors and walls were collected in winter. The blood was taken in spring the following year, from 40 men, 26 to 53 years old, healthcare workers of hospital emergency departments (HED), who had been working for at least five years in their current positions, and from 36 corresponding controls, working in control offices. Evaluation of blood leukocyte subpopulations was done by flow cytometry. The qualitative analysis of the surface samples revealed a prevalence of strains belonging to Aspergillus spp. and Penicillium spp. genus. There was no statistically significant difference between the level of NKT; however, the percentage of NK cells was lower in the blood of HED workers than in the blood of offices personnel. Spearman analysis revealed the existence of positive correlation (r = 0.4677, p = 0.002) between the total CFU/25 cm(2) obtained by imprinting method from walls and floors of HED and the percentage of NKT (CD3(+)16(+)56(+)) lymphocytes collected from the blood of their personnel, and negative correlation (r = -0. 3688, p = 0.019) between this parameter of fungal pollution and the percentage of CD4(+) lymphocytes in the blood of HED staff. No other correlations were found. PMID:27095925

  6. Assessment of Some Immune Parameters in Occupationally Exposed Nuclear Power Plants Workers: Flowcytometry Measurements of T, B, NK and NKT Cells.

    Science.gov (United States)

    Gyuleva, Ilona; Panova, Delyana; Djounova, Jana; Rupova, Ivanka; Penkova, Kalina

    2015-01-01

    The purpose of this article is to analyze the results of a 10-year survey of the radiation effects of some immune parameters of occupationally exposed personnel from the Nuclear Power Plant "Kozloduy", Bulgaria. 438 persons working in NPP with cumulative doses between 0.06 mSv and 766.36mSv and a control group with 65 persons were studied. Flow cytometry measurements of T, B, natural killer (NK) and natural killer T (NKT) cell lymphocyte populations were performed. Data were interpreted with regard to cumulative doses, length of service and age. The average values of the studied parameters of cellular immunity were in the reference range relative to age and for most of the workers were not significantly different from the control values. Low doses of ionizing radiation showed some trends of change in the number of CD3+CD4+ helper-inducer lymphocytes, CD3+ CD8+ and NKT cell counts. The observed changes in some of the studied parameters could be interpreted in terms of adaptation processes at low doses. At doses above 100-200 mSv, compensatory mechanisms might be involved to balance deviations in lymphocyte subsets. The observed variations in some cases could not be attributed only to the radiation exposure because of the impact of a number of other exogenous and endogenous factors on the immune system. PMID:26675014

  7. 睾丸的原发性NK/T细胞淋巴瘤一例报告及文献复习%Primary NK/T cell lymphoma of the testis:A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To study the clinical and pathological features of primary NK/T cell lymphoma of testis and to investigate the effective diagnosis and treatment of this disease. Methods: The surgical specimens of a patient with primary NK/T cell lymphoma of the testis were observed by light microscopy, immunohistochemistry and examined by the polymerase chain reaction (PCR) for Epstein-Barr virus (EBV) DNA and T-cell receptor (TCR) gene rearrangement, and the literature were reviewed. Results: The patient presented with left-sided painless testicular enlargement and the lymphoma had a propensity to spread to the contralateral testis, spleen, central nervous system, and so on. The neoplastic cells were positive for CD56,CD45R0 and CD3ε, while the expressions of CD20, CD79α, CD5, Bcl-2 and PLAP were negative. In addition, the EBV DNA was detected in the lymphoma by PCR. And the results of gene rearrangement studies for the Y chain of the T-cell receptor were negative. The pathological diagnosis was NK/T cell lymphoma of the left testis. Conclusion: Primary NK/T cell lymphoma of the testis is a rare entity and progressed rapidly. The histopathological, immunohistochemical, EBV examination and TCR gene rearrangement studies should be carried out as soon as possible in order to get the defined diagnosis. Currently,the therapeutic efficacy is poor and the new measures should be investigated to improve the survival rate.

  8. Maternal low protein diet leads to dysregulation of placental iNKT cells and M1/M2 macrophage ratio, body weight loss in male, neonate Sprague-Dawley rats and increased UCP-1 mediated thermogenesis

    Science.gov (United States)

    Placental immune cells provide cytokines and growth factors that are necessary for placenta development and function. Invariant natural killer T (iNKT) cells are innate cells specific for glycolipid antigens presented by the CD1d molecule and secrete Th1 cytokines in the placenta, suggesting an imm...

  9. Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice.

    Science.gov (United States)

    Satoh, Masashi; Hoshino, Miyuki; Fujita, Koki; Iizuka, Misao; Fujii, Satoshi; Clingan, Christopher S; Van Kaer, Luc; Iwabuchi, Kazuya

    2016-01-01

    It has been shown that CD1d expression and glycolipid-reactive, CD1d-restricted NKT cells exacerbate the development of obesity and insulin resistance in mice. However, the relevant CD1d-expressing cells that influence the effects of NKT cells on the progression of obesity remain incompletely defined. In this study, we have demonstrated that 3T3-L1 adipocytes can present endogenous ligands to NKT cells, leading to IFN-γ production, which in turn, stimulated 3T3-L1 adipocytes to enhance expression of CD1d and CCL2, and decrease expression of adiponectin. Furthermore, adipocyte-specific CD1d deletion decreased the size of the visceral adipose tissue mass and enhanced insulin sensitivity in mice fed a high-fat diet (HFD). Accordingly, NKT cells were less activated, IFN-γ production was significantly reduced, and levels of adiponectin were increased in these animals as compared with control mice on HFD. Importantly, macrophage recruitment into the adipose tissue of adipocyte-specific CD1d-deficient mice was significantly blunted. These findings indicate that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. PMID:27329323

  10. IL-15 Superagonist Expands mCD8+ T, NK and NKT Cells after Burn Injury but Fails to Improve Outcome during Burn Wound Infection.

    Directory of Open Access Journals (Sweden)

    Naeem K Patil

    Full Text Available Severely burned patients are highly susceptible to opportunistic infections and sepsis, owing to the loss of the protective skin barrier and immunological dysfunction. Interleukin-15 (IL-15 belongs to the IL-2 family of common gamma chain cytokines and stimulates the proliferation and activation of T (specifically memory CD8, NK and NKT cells. It has been shown to preserve T cell function and improve survival during cecal ligation and puncture (CLP-induced sepsis in mice. However, the therapeutic efficacy of IL-15 or IL-15 superagonist (SA during infection after burn injury has not been evaluated. Moreover, very few, if any, studies have examined, in detail, the effect of burn injury and infection on the adaptive immune system. Thus, we examined the effect of burn and sepsis on adaptive immune cell populations and the effect of IL-15 SA treatment on the host response to infection.Mice were subjected to a 35% total body surface area burn, followed by wound infection with Pseudomonas aeruginosa. In some experiments, IL-15 SA was administered after burn injury, but before infection. Leukocytes in spleen, liver and peritoneal cavity were characterized using flow cytometry. Bacterial clearance, organ injury and survival were also assessed.Burn wound infection led to a significant decline in total white blood cell and lymphocyte counts and induced organ injury and sepsis. Burn injury caused decline in CD4+ and CD8+ T cells in the spleen, which was worsened by infection. IL-15 treatment inhibited this decline and significantly increased cell numbers and activation, as determined by CD69 expression, of CD4+, CD8+, B, NK and NKT cells in the spleen and liver after burn injury. However, IL-15 SA treatment failed to prevent burn wound sepsis-induced loss of CD4+, CD8+, B, NK and NKT cells and failed to improve bacterial clearance and survival.Cutaneous burn injury and infection cause significant adaptive immune dysfunction. IL-15 SA does not augment host

  11. CD1d-dependent NKT cells play a protective role in acute and chronic arthritis models by ameliorating antigen-specific Th1 responses

    DEFF Research Database (Denmark)

    Teige, Anna; Bockermann, Robert; Hasan, Maruf;

    2010-01-01

    A protective and anti-inflammatory role for CD1d-dependent NKT cells (NKTs) has been reported in experimental and human autoimmune diseases. However, their role in arthritis has been unclear, with conflicting reports of CD1d-dependent NKTs acting both as regulatory and disease-promoting cells...... in arthritis. These differing modes of action might be due to genetic differences of inbred mice and incomplete backcrossing of gene-modified mice. We therefore put special emphasis on controlling the genetic backgrounds of the mice used. Additionally, we used two different murine arthritis models, Ag......-induced arthritis (AIA) and collagen-induced arthritis (CIA), to evaluate acute and chronic arthritis in CD1d knockout mice and mice depleted of NK1.1(+) cells. CD1d-deficient mice developed more severe AIA compared with wild-type littermates, with a higher degree of inflammation and proteoglycan depletion. Chronic...

  12. Human Invariant Natural Killer T cells possess immune-modulating functions during Aspergillus infection.

    Science.gov (United States)

    Beitzen-Heineke, Antonia; Bouzani, Maria; Schmitt, Anna-Lena; Kurzai, Oliver; Hünniger, Kerstin; Einsele, Hermann; Loeffler, Juergen

    2016-02-01

    Aspergillus fumigatus is the most common cause for invasive fungal infections, a disease associated with high mortality in immune-compromised patients. CD1d-restricted invariant natural killer T (iNKT) cells compose a small subset of T cells known to impact the immune response toward various infectious pathogens. To investigate the role of human iNKT cells during A. fumigatus infection, we studied their activation as determined by CD69 expression and cytokine production in response to distinct fungal morphotypes in the presence of different CD1d(+) antigen presenting cells using flow cytometry and multiplex enzyme-linked immunosorbent assay (ELISA). Among CD1d(+) subpopulations, CD1d(+)CD1c(+) mDCs showed the highest potential to activate iNKT cells on a per cell basis. The presence of A. fumigatus decreased this effect of CD1d(+)CD1c(+) mDCs on iNKT cells and led to reduced secretion of TNF-α, G-CSF and RANTES. Production of other Th1 and Th2 cytokines was not affected by the fungus, suggesting an immune-modulating function for human iNKT cells during A. fumigatus infection.

  13. 狼疮性肾炎患者外周血中调节性T细胞与NKT细胞变化的研究%Patients with lupus nephritis regulatory cells and NKT cells in peripheral blood of change research

    Institute of Scientific and Technical Information of China (English)

    张羽; 杨秀华; 朱文静; 郭存丽

    2015-01-01

    目的 观察狼疮性肾炎(LN)患者外周血中的CD4+ CD25+调节性T细胞(Tregs)、NK/NKT细胞变化规律及其与LN的关系,并探讨其意义.方法 选择系统性红斑狼疮患者(无肾脏受累)17例,狼疮性肾炎患者23例,健康志愿者24例,分别做为SLE组、LN组和对照组.应用流式细胞仪检测其外周血中CD4+ CD25+ Tregs、CD3+ CD57+ NKT细胞、CD3-CD57+NKT细胞、CD3+ CD56+ NKT细胞、CD3-CD56+ NKT细胞、CD3-CD20+B细胞,并且对狼疮性肾炎患者进行肾脏活检以及尿蛋白、抗核抗体等检测.结果 LN组外周血中CD4+ CD25+ Tregs比例显著低于对照组(t=1.99,P=0.03),CD3+ CD57+ NKT细胞群比例显著高于对照组(t=1.98,P=0.02);CD3-CD57+ NKT细胞、CD3+ CD56+NKT细胞、CD3-CD56+ NKT细胞、CD3-CD20+B细胞变化不明显.结论 CD4+ CD25+ Tregs是阻止LN发生和发展的关键,CD3+ CD57+ NKT细胞对LN患者的肾脏受损起重要作用.%Objective To investigate the ratios of CD4 + CD25 + regulatory cells (Tregs) and NK/NKT cells in peripheral blood of patients of lupus nephritis and to explore their contribution on the pathogenesis of lupus nephritis.Methods Patients of systemic lupus erythematosus (SLE) with no renal involvement,lupus nephritis and healthy controls were studied.Flow cytometry was utilized to quantify the percentage of CD4 + CD25 + Tregs,CD3 + CD57 + NKT cells,CD3-CD57 + NK,CD3 + CD56 + NKT cells,CD3-CD56 + NK cells and CD3-CD20 + B cells in peripheral blood.Renal biopsy was performed for patients with lupus nephritis.Urine protein and antinuclear antibody were also detected.Results The mean percentage of CD4 + CD25 + Tregs in the peripheral blood of patients with lupus nephritis was significantly lower than the control group (t =1.99,P =0.03),while CD3+ CD57+ NKT from lupus nephritis was significantly higher compared with control (t =1.98,P =0.02).However,levels of CD3-CD57 + NKT cells,CD3 + CD56 + NKT cells,CD3-CD56 + NKT cells and CD3-CD20 + B cells did not show a

  14. 鼻腔NK/T细胞淋巴瘤的影像学诊断%Diagnosis of Primary Nasal Cavity NK/T Cell Lymphoma

    Institute of Scientific and Technical Information of China (English)

    张宽; 彭通略

    2011-01-01

    目的 探讨鼻腔NK/T细胞淋巴瘤的CT及MRI表现特征.材料和方法 回顾性分析21例经病理证实的鼻腔NK/T细胞淋巴瘤患者的CT和MRI影像学资料及临床资料.结果 本组21例中单侧7例,双侧14例,依据病变范围将本病分为局限型和弥漫型两种类型.局限型13例,主要位于鼻腔内,其中鼻腔前部11例,鼻腔后部2例;骨质改变不明显,浸润鼻旁或面部皮下组织9例,弥漫型8例,肿瘤范围广泛并向鼻腔周围结构浸润扩展,其中累及鼻旁窦7例,侵入眼眶1例、颞下窝2例,延伸至鼻咽、口咽部并累及咽旁间隙6例,骨质破坏7例,颈部淋巴结受累1例.CT显示肿瘤呈软组织密度充填鼻腔并沿鼻黏膜蔓延,增强后轻到中度不均匀强化.MRI T1WI肿瘤呈等信号,信号强度类似或稍低于肌肉;T2WI呈不均匀稍高信号,信号强度高于肌肉,但低于鼻黏膜,增强后轻到中度不均匀强化.结论 鼻腔NK/T细胞型淋巴瘤影像学表现有一定特征,CT、MRI检查可提示诊断,有利于确定病变范围及临床分期.%Purpose To characterize CT and MRI features of primary nasal cavity NK/T cell non-Hodgkin's lymphoma. Materials and Methods CT or/and MRI findings of 21 cases with nasal cavity NK/T cell lymphoma verified by pathologically were analyzed retrospectively. Results Of all 21 cases, 7 were involved in unilateral nasal cavity, 14 were involved in bilateral nasal cavity. Nasal cavity NK/T cell lymphoma was divided into localized type and diffuse type according to the range of lesion. A total of 13 cases were localized type, mainly located in the nasal cavity, 11 of them located in front of the nasal cavity, 2 located in posterior nasal cavity, bone mass showed no obvious change, 9 were involved in paranasal or facial subcutaneous tissue. A total of 8 cases were diffuse type, the lesion was involved extensively and infiltrated to the adjacent structures of nasal cavity, 7 cases among them involved the paranasal

  15. 早期鼻腔NK/T细胞淋巴瘤放疗模式的研究现状%Current study status of radiotherapy modality on early stage nasal NK/T cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    韩宝林

    2012-01-01

    鼻腔NK/T细胞淋巴瘤属于结外非霍奇金淋巴瘤的一种少见特殊类型,目前研究已经确立了放疗在其治疗中的地位和作用,但对于具体的放疗模式,如适宜的放疗靶区、放疗剂量以及颈部预防照射等问题仍存在着较大的争议.多数研究表明扩大野放疗和较高的放疗剂量是取得较好放疗疗效的关键;局限期病例多不主张颈部预防照射,但对于病变范围广泛者仍有较大争论.%Nasal NK/T cell lymphoma is a rare and distinct type of extranodal Non-Hodgkin' s lymphoma. Current study has proved that Radiotherapy is the most effective treatment method in the early stage nasal NK/T cell lymphoma, but there is no universal standard for concrete radiotherapy modality, such as the radiation target, the radiation dose and preventive neck radiation. Most studies have proved that radiotherapy of extended field and higher dose achieved good effect in early stage nasal NK/T cell lymphoma.And the studies also do not suggested preventive neck radiation in local stage patients, but it need further study in the extensive stage patients.

  16. A novel synthetic immunostimulator CH1a containing thiazolidin-4-one enhances the function of human iNKT cells in vitro%新型合成的免疫调节剂CH1a促进人iNKT细胞功能的研究

    Institute of Scientific and Technical Information of China (English)

    孟明; 王泽瑞; 李春晓; 韩华; 史建红; 陈华; 李小六; 陈冬志

    2013-01-01

    Objective To investigate the immunoregulatory effects of a novel synthetic immunostimulator CH1a containing thiazolidin-4-one on the function of human iNKT(invariant nature killer T) cells in vitro.Methods Peripheral blood mononuclear cells (PBMCs) from healthy adults were cultured with stimulation of α-Galcer and IL-2 in vitro,and iNKT cells were then separated by using magnetic-activated cell sorting (MACS) method with iNKT isolation kit.The effects of CH1a on the proliferation of iNKT cells were analyzed by using MTY assay.51Cr release assay was used to evaluate the killing activity of iNKT cells to K562 cells.Fluorescence-activated cell sorting (FACS) was used to detect the proliferation of iNKT cells,as well as the production of IFN-γ and IL-4.Results CH1a was found to significantly stimulate the iNKT proliferation (mainly up to 4-7 generations),promote the secretion of both IFN-γand IL-4,and increase the ratio of IFN-γ/IL-4.More importantly,CH1a could markedly enhance the cytotoxicity of iNKT cells.Conclusion Immunostimulator CH1a could promote the production of Th1-like cytokines by iNKT cells and induce differentiation of Th0 to Th1 cells.Moreover,CH1a could significantly enhance the cytotoxicity of iNKT cells.%目的 研究新型合成的含噻唑烷-4-酮环的免疫调节剂CH1a对人类iNKT(invariant nature killer T)细胞功能的影响.方法 从健康人外周血分离单个核淋巴细胞(PBMC),经α-Galcer和IL-2体外刺激扩增后利用iNKT分离试剂盒经磁珠分选(MACS)得到纯化的iNKT细胞.采用MTT法定量测定CH1a对iNKT细胞增殖的影响,利用51Cr释放实验观察iNKT细胞对K562细胞杀伤率的影响;利用流式细胞技术检测iNKT细胞增殖分代及细胞因子(IFN-γ和IL-4)的表达.结果 CH1a能显著促进纯化的iNKT细胞体外增殖(以4~7代细胞数居多);并增加IFN-γ和IL-4的释放且显著提高IFN-γ/IL-4比值;尤其是CH1a能显著提高iNKT细胞的杀伤活性.结论

  17. 免疫调节剂CH2b对活动期类风湿关节炎患者iNKT细胞免疫调节功能的影响%Effects of a novel synthetic immunostimulator CH2b on iNKT cells isolated from patients with active rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    孟明; 杨飞; 许鸣华; 陈丹; 候明辉; 刘嘉琳; 陈冬志

    2015-01-01

    Objective To investigate the effects of a novel synthetic immunostimulator CH2b containing thiazolidin-4-one on the function of invariant nature killer T (iNKT) cells isolated from patients with active rheumatoid arthritis (RA).Methods Peripheral blood mononuclear cells (PBMCs) isolated from patients with active RA were in vitro cultured with α-Galcer and IL-2.The iNKT cells were separated by using magnetic activated cell sorting (MACS) method.The effects of CH2b on the proliferation of iNKT cells were analyzed by using MTT assay.MILLIPLEX MAP Human Cytokine/Chemokine kit was used to measure the levels of IFN-γ and IL-4 in the supernatants of iNKT cell culture.The expressions of IFN-γand IL-4 at mRNA level in iNKT cells were analyzed by RT-PCR.Western blot assay was used to detect the levels of T-bet and GATA-3 in iNKT cells.Results CH2b significantly enhanced the proliferation of IL-2 activated iNKT cells isolated from the patients with active RA.CH2b promoted the secretion of IL-4,resulting in a decrease in the ratio of IFN-γ/IL-4.Moreover,CH2b promoted the expressions of GATA-3 and IL-4 at mRNA level in iNKT cells.Conclusion The novel immunostimulator,CH2b,might enhance the immunoregulatory effects of iNKT cells by promoting the GATA-3 pathway-mediated secretion of Th2-1ike cytokines and inducing the differentiation of Th0 to Th2 cells.%目的 研究新型合成的含噻唑烷-4-酮的免疫调节剂CH2b对活动期类风湿关节炎(RA)患者iNKT(invariant nature killer T)细胞功能的影响.方法 外周血单个核细胞(PBMC)分离自活动期RA患者,经α-Galcer和IL-2体外刺激扩增后利用iNKT分离试剂盒经磁珠分选(MACS)得到纯化的iNKT细胞;采用MTT法定量测定CH2b对iNKT细胞增殖的影响;MILLIPLEX MAP Human Cytokine/Chemokine kit检测相应iNKT细胞培养上清中IFN-γ/IL-4的水平;RT-PCR检测iNKT细胞中IFN-γ mRNA与IL-4 mRNA表达水平;Western blot检测iNKT细胞中T-bet/GATA-3表达水平.结果 CH2b

  18. TLR9-induced miR-155 and Ets-1 decrease expression of CD1d on B cells in SLE.

    Science.gov (United States)

    Liu, Fei; Fan, Hongye; Ren, Deshan; Dong, Guanjun; Hu, Erling; Ji, Jianjian; Hou, Yayi

    2015-07-01

    B cells present lipid antigens to CD1d-restricted invariant natural killer T (iNKT) cells to maintain autoimmune tolerance, and this process is disrupted in systemic lupus erythematosus (SLE). Inflammation may inhibit CD1d expression to exacerbate the pathology of lupus. However, how inflammation regulates CD1d expression on B cells is unclear in SLE. In the present study, we showed that the surface expression of CD1d on B cells from SLE mice was decreased and that stimulation of inflammatory responses through TLR9 decreased the membrane and total CD1d levels of CD1d on B cells. Moreover, inflammation-related microRNA-155 (miR-155) negatively correlated with the expression of CD1d in B cells. miR-155 directly targeted the 3'-untranslated region (3'-UTR) of CD1d upon TLR9 activation in both humans and mice. The inhibitory effects of miR-155 on CD1d expression in B cells impaired their antigen-presenting capacity to iNKT cells. In addition, Ets-1, a susceptibility gene of SLE, also directly regulated the expression of the CD1d gene at the transcriptional level. These findings provide new insight into the mechanism underlying decreased CD1d expression on B cells in SLE, suggesting that inhibition of inflammation may increase CD1d expression in B cells to ameliorate SLE via modulating iNKT cells. PMID:25929465

  19. TLR9-induced miR-155 and Ets-1 decrease expression of CD1d on B cells in SLE.

    Science.gov (United States)

    Liu, Fei; Fan, Hongye; Ren, Deshan; Dong, Guanjun; Hu, Erling; Ji, Jianjian; Hou, Yayi

    2015-07-01

    B cells present lipid antigens to CD1d-restricted invariant natural killer T (iNKT) cells to maintain autoimmune tolerance, and this process is disrupted in systemic lupus erythematosus (SLE). Inflammation may inhibit CD1d expression to exacerbate the pathology of lupus. However, how inflammation regulates CD1d expression on B cells is unclear in SLE. In the present study, we showed that the surface expression of CD1d on B cells from SLE mice was decreased and that stimulation of inflammatory responses through TLR9 decreased the membrane and total CD1d levels of CD1d on B cells. Moreover, inflammation-related microRNA-155 (miR-155) negatively correlated with the expression of CD1d in B cells. miR-155 directly targeted the 3'-untranslated region (3'-UTR) of CD1d upon TLR9 activation in both humans and mice. The inhibitory effects of miR-155 on CD1d expression in B cells impaired their antigen-presenting capacity to iNKT cells. In addition, Ets-1, a susceptibility gene of SLE, also directly regulated the expression of the CD1d gene at the transcriptional level. These findings provide new insight into the mechanism underlying decreased CD1d expression on B cells in SLE, suggesting that inhibition of inflammation may increase CD1d expression in B cells to ameliorate SLE via modulating iNKT cells.

  20. Ambulanssjuksköterskans tankar och upplevelser av att SMS-livräddare varit först på plats vid misstänkt hjärtstopp : En kvalitativ intervju studie

    OpenAIRE

    Norén, David; Soldemo, Marlene

    2014-01-01

    SAMMANFATTNING Bakgrund: Det finns mycket skrivet om SMS-livräddning och studier har påvisat att det räddar liv, inga studier beskriver hur ambulanssjuksköterskan upplever mötet med SMS-livräddaren. Syfte: Att beskriva ambulanssjuksköterskans tankar och upplevelser av att SMS-livräddare varit först på plats vid misstänkt hjärtstopp. Metod: En kvalitativ intervjustudie med 6 deltagare. Resultat: Det framkom både positiva och negativa tankar och upplevelser i mötet med SMS-livräddaren. SMS-livr...

  1. CRISPR-Mediated Slamf1Δ/Δ Slamf5Δ/Δ Slamf6Δ/Δ Triple Gene Disruption Reveals NKT Cell Defects but Not T Follicular Helper Cell Defects

    Science.gov (United States)

    Hu, Joyce K.; Crampton, Jordan C.; Locci, Michela; Crotty, Shane

    2016-01-01

    SAP (SH2D1A) is required intrinsically in CD4 T cells to generate germinal center responses and long-term humoral immunity. SAP binds to SLAM family receptors, including SLAM, CD84, and Ly108 to enhance cytokine secretion and sustained T cell:B cell adhesion, which both improve T follicular helper (Tfh) cell aid to germinal center (GC) B cells. To understand the overlapping roles of multiple SLAM family receptors in germinal center responses, Slamf1Δ/Δ Slamf5Δ/Δ Slamf6Δ/Δ triple gene disruption (Slamf1,5,6Δ/Δ) mice were generated using CRISPR-Cas9 gene editing to eliminate expression of SLAM (CD150), CD84, and Ly108, respectively. Gene targeting was highly efficient, with 6 of 6 alleles disrupted in 14 of 23 pups and the majority of alleles disrupted in the remaining pups. NKT cell differentiation in Slamf1,5,6Δ/Δ mice was defective, but not completely absent. The remaining NKT cells exhibited substantially increased 2B4 (SLAMF4) expression. Surprisingly, there were no overt defects in germinal center responses to acute viral infections or protein immunizations in Slamf1,5,6Δ/Δ mice, unlike Sh2d1a-/- mice. Similarly, in the context of a competitive environment, SLAM family receptor expressing GC Tfh cell, GC B cell, and plasma cell responses exhibited no advantages over Slamf1,5,6Δ/Δ cells. PMID:27223891

  2. Generation and characterization of CD1d-specific single-domain antibodies with distinct functional features.

    Science.gov (United States)

    Lameris, Roeland; de Bruin, Renée C G; van Bergen En Henegouwen, Paul M P; Verheul, Henk M; Zweegman, Sonja; de Gruijl, Tanja D; van der Vliet, Hans J

    2016-09-01

    Ligation of the CD1d antigen-presenting molecule by monoclonal antibodies (mAbs) can trigger important biological functions. For therapeutic purposes camelid-derived variable domain of heavy-chain-only antibodies (VHH) have multiple advantages over mAbs because they are small, stable and have low immunogenicity. Here, we generated 21 human CD1d-specific VHH by immunizing Lama glama and subsequent phage display. Two clones induced maturation of dendritic cells, one clone induced early apoptosis in CD1d-expressing B lymphoblasts and multiple myeloma cells, and another clone blocked recognition of glycolipid-loaded CD1d by CD1d-restricted invariant natural killer T (iNKT) cells. In contrast to reported CD1d-specific mAbs, these CD1d-specific VHH have the unique characteristic that they induce specific and well-defined biological effects. This feature, combined with the above-indicated general advantages of VHH, make the CD1d-specific VHH generated here unique and useful tools to exploit both CD1d ligation as well as disruption of CD1d-iNKT interactions in the treatment of cancer or inflammatory disorders. PMID:27312006

  3. Effcets on immunoregulation of iNKT cells in RA by novel synthetic immunos-timulator CH1 b%含噻唑烷-4-酮的免疫调节剂对RA患者iNKT细胞免疫调节功能的影响

    Institute of Scientific and Technical Information of China (English)

    孟明; 张雪娇; 瓮沛杉; 许鸣华; 陈丹; 侯明辉; 陈冬志

    2016-01-01

    Objective:To investigate effects of a novel synthetic immunostimulator CH1b containing thiazolidin-4-one on the immunoregulation funotion of iNKT ( invariant nature killer T ) cells in active RA patients in vitro.Methods: Peripheral blood mononuclear cells( PBMCs) isolated from active RA patients were cultured with stimulation of α-Galcer and IL-2 in vitro and iNKT cells were then separated by using magnetic activated cell sorting( MACS) method with iNKT isolation kit.The cells were divided into three groups:control group (IL-2),α-Galcer group (IL-2+α-Galcer),CH1b group(IL-2 +CH1b).The effects of CH1b on the proliferation of iNKT cells in active RA patients were analyzed by using MTT assay.MILLIPLEX MAP Human Cytokine/Chemokine kit was used to evaluate the secretion of IFN-γand IL-4 in iNKT cells culture media.The expressions of IFN-γmRNA and IL-4 mRNA in iNKT cells were analyzed by RT-PCR.Results: Compared with control and α-Galcer group,the proliferation of iNKT cells of CH1b group were significantly higher( P<0.05).Compared with control,the ratio of IFN-γ/IL-4 in iNKT cells culture media in active RA patients of CH1b group were significantly lower (P<0.05).Compared with control,expressions of IFN-γmRNA and IL-4 mRNA were higher inα-Galcer group;compared with control,expressions of IL-4 mRNA were higher in CH1b group,while there were no obvious difference on expressions of IFN-γmRNA.Conclusion:CH1b was found to significantly stimulate the actived iNKT cells in active RA patients proliferation,promote the secretion of IL-4,and increase the ratio of IFN-γ/IL-4,promote the expression of IL-4 mRNA in iNKT cells in active patients.%目的:研究新型合成的含噻唑烷-4-酮的免疫调节剂(CH1b)对活动期RA患者iNKT细胞免疫调节功能的影响。方法:从RA患者外周血中分离得到单个核淋巴细胞( PBMC),α-Galcer和IL-2体外刺激扩增后,经磁珠分选( MACS)得到纯化的iNKT细胞,分成对照组(IL-2

  4. Phenotypic and functional features of NK and NKT cells in chronic hepatitis B%NK细胞和NKT细胞在慢性乙型肝炎中的表型和功能特征

    Institute of Scientific and Technical Information of China (English)

    吴韶飞; 李曼; 孙学华; 周振华; 朱晓骏; 张鑫; 高月求

    2015-01-01

    目的 检测慢性乙型肝炎(CHB)患者外周血自然杀伤(NK)细胞、自然杀伤T(NKT)细胞的比例、NKG2D/NKG2A水平和γy干扰素(IFN-γ)、肿瘤坏死因子α(TNF-α)的水平.方法 采集并分离CHB患者外周血单个核细胞(PBMC),流式细胞术检测NK、NKT细胞占PBMC的比例,NKG2D、NKG2A水平,经佛波酯(PMA)、布雷菲德菌素A(BFA)、离子霉素(ionomycin)处理后,流式细包术检测IFN-γ、TNF-α的水平,分析各指标与乙肝病毒载量和血清丙氨酸氨基转移酶的关系,采用独立样本t检验与Pearson相关性分析.结果 与正常对照者相比,CHB患者外周血NK细胞和NKT细胞比例明显降低;NKG2A阳性的NK细胞和NKT细胞明显升高;经PMA、BFA、ionomycin刺激后,IFN-γ阳性的NK细胞和NKT细胞明显降低.结论 CHB患者NK、NKT细胞存在不同程度的减少、受体表达失调和细胞因子分泌功能下降等功能紊乱.

  5. Influence of In Vitro IL-2 or IL-15 Alone or in Combination with Hsp 70 Derived 14-Mer Peptide (TKD on the Expression of NK Cell Activatory and Inhibitory Receptors on Peripheral Blood T Cells, B Cells and NKT Cells.

    Directory of Open Access Journals (Sweden)

    Ilona Hromadnikova

    Full Text Available Previous studies from Multhoff and colleagues reported that plasma membrane Hsp70 acts as a tumour-specific recognition structure for activated NK cells, and that the incubation of NK cells with Hsp70 and/or a 14-mer peptide derived from the N-terminal sequence of Hsp70 (TKDNNLLGRFELSG, TKD, aa 450-463 plus a low dose of IL-2 triggers NK cell proliferation and migration, and their capacity to kill cancer cells expressing membrane Hsp70. Herein, we have used flow cytometry to determine the influence of in vitro stimulation of peripheral blood mononuclear cells from healthy individuals with IL-2 or IL-15, either alone or in combination with TKD peptide on the cell surface expression of CD94, NK cell activatory receptors (CD16, NK2D, NKG2C, NKp30, NKp44, NKp46, NKp80, KIR2DL4, DNAM-1 and LAMP1 and NK cell inhibitory receptors (NKG2A, KIR2DL2/L3, LIR1/ILT-2 and NKR-P1A by CD3+CD56+ (NKT, CD3+CD4+, CD3+CD8+ and CD19+ populations. NKG2D, DNAM-1, LAMP1 and NKR-P1A expression was upregulated after the stimulation with IL-2 or IL-15 alone or in combination with TKD in NKT, CD8+ T cells and B cells. CD94 was upregulated in NKT and CD8+ T cells. Concurrently, an increase in a number of CD8+ T cells expressing LIR1/ILT-2 and CD4+ T cells positive for NKR-P1A was observed. The proportion of CD8+ T cells that expressed NKG2D was higher after IL-2/TKD treatment, when compared with IL-2 treatment alone. In comparison with IL-15 alone, IL-15/TKD treatment increased the proportion of NKT cells that were positive for CD94, LAMP1 and NKRP-1A. The more potent effect of IL-15/TKD on cell surface expression of NKG2D, LIR1/ILT-2 and NKRP-1A was observed in B cells compared with IL-15 alone. However, this increase was not of statistical significance. IL-2/TKD induced significant upregulation of LAMP1 in CD8+ T cells compared with IL-2 alone. Besides NK cells, other immunocompetent cells present within the fraction of peripheral blood mononuclear cells were influenced by

  6. 鼻咽NK/T细胞淋巴瘤肿瘤相关巨噬细胞与其增殖活性的关系%The relation between tumor associated macrophages and the proliferative activity of tumor cells in nasopharyngeal NK/T cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    刘一雄; 王映梅; 李培峰; 范林妮; 朱瑾; 王璐; 张微晨; 张月华; 黄高昇

    2012-01-01

    目的:研究鼻咽NK/T细胞淋巴瘤中肿瘤相关巨噬细胞(TAMs)数量与肿瘤增殖指数,以及2种巨噬细胞标志物(CD68与CD163)间的关系.方法:采用免疫组织化学染色法检测31例鼻咽NK/T细胞淋巴瘤和12例炎性反应病例的Ki67,CD68以及CD163.并对染色结果进行Pearson相关分析和t检验.结果:鼻咽NK/T细胞淋巴瘤中的TAMs数与肿瘤的增殖活性具有非常显著的正相关性(P=0.024),同时,CD163与CD68阳性细胞数密切相关(P =0.009),CD68的阳性率略高于CD163,但无统计学意义.鼻咽NK/T细胞淋巴瘤中TAMs的数量,与反应性病变相比具有明显差异(P<0.05).结论:鼻咽NK/T细胞淋巴瘤中的TAMs与肿瘤细胞增殖活性密切相关,表明TAMs可促进NK/T细胞淋巴瘤细胞的增殖.并且2种标志物(CD68及CD163)均可识别TAMs.而CD163为TAMs的标志物似乎更加准确.%Objective; To explore the relationship between the number of tumor - associated macrophages (TAMs) and proliferative activity of tumor cells and the relationship between two macrophage biomarkers CD68 and CD163 in nasopharyngeal NK/T cell lymphoma. Methods: Immunohistochemistry was used to reconfirm the diagnosis of nasal NK/T - cell lymphoma and detect the numbers of TAMs and the ki - 67 label index of the tumor cells in all 31 patients. In addition, 12 cases of inflammatory cases were collected as controls, for which the immunostaining of CD68 and CD163 were done as well. Results;The number of TAMs was positively correlated with tumor proliferative activity( P =0.024) in nasopharyngeal NK/T cell lymphoma. The expression of CD68 and CD163 were closely related (P = 0.009), and the positive rate of CD68 was generally higher than CD163,however there was no statistical significance. Conclusion:The increase in numbers of TAMs in nasopharyngeal NK/T cell lymphoma often relates with higher proliferative index,indicating the TAMs play an important role in tumor proliferation. Meanwhile both CD68 and CD

  7. 食管癌患者外周血中自然杀伤性T细胞含量的检测及其临床意义%NKT cells in peripheral blood of patients with esophageal carcinoma and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    路鹏; 苏文; 王艳峰; 马克蓉; 张羽捷

    2010-01-01

    目的 研究食管癌患者外周血中自然杀伤性(NK)T细胞在手术前后的表达情况.方法 采用流式细胞术(FCM)分析59例食管癌患者手术前后外周血中CD3、CD56、CD4、CD8抗体的表达,研究NKT细胞及其亚群的表达情况及所占比例.结果 随着CD+3 CD+56 CD+8/CD+3 CD+56 CD+4的比值逐渐升高,Ⅲ~Ⅳ期食管癌患者的比例逐渐降低,ANOVA示组间差异有统计学意义(P<0.05);CD+3 CD+56 CD+8/CD+3CD+56 CD+4的比值与CD+3 CD+56 CD+4NKT细胞非线性相关;CD+3 CD+56 CD+8 NKT细胞与NK细胞正相关,与CD+3T细胞负相关.结论 CD+3 CD+56 CD+8/CD+3 CD+56 CD+4的比值可能与肿瘤负荷有关,并且有助于判断食管癌患者的疾病程度及预后.%Objective To explore the expression, as well as the proportion of subsets of the natural killer (NK) T cells in peripheral blood of patients with esophageal carcinoma before and after surgery, and provide ideas and experimental basis for immune treatment through tests. Methods Using CD3, CD56, CD4 and CD8 antibody to study the NKT cells and its subsets. Peripheral NKT cell subsets in 59 patients with esophageal carcinoma were analysed by flow cytometer. Results With the ratio of CD+3 CD+56 CD+8/CD+3 CD+56 CD+4 gradually increased, the proportion of phase Ⅲ- Ⅳ patients with esophageal carcinoma is gradually decreased between the groups. One-way ANOVA analysis showed that there were differences between the groups (P <0.05). The ratio of CD+3 CD+56 CD+8/CD+3 CD+56 CD+4 was in Non-linear related to CD+3 CD+56 CD+4NKT cells; CD+3 CD+56 CD+8; NKT cells were positively correlated with CD-3 CD+56 NK cells and negatively correlated with CD+3 T cells.Conclusion The ratio of CD+3 CD+56 CD+8/CD+3 CD+56 CD+4 may relate to tumor burden, and is helpful to determine the extent of disease in patients with esophageal carcinoma and prognosis.

  8. Soluble triggering receptor expressed on myeloid cells 1: a biomarker for bacterial meningitis

    NARCIS (Netherlands)

    R.M. Determann; M. Weisfelt; J. de Gans; A. van der Ende; M.J. Schultz; D. van de Beek

    2006-01-01

    Objective: To evaluate whether soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in CSF can serve as a biomarker for the presence of bacterial meningitis and outcome in patients with this disease. Design: Retrospective study of diagnostic accuracy. Setting and patients: CSF was coll

  9. Clinical analysis of 27 cases with nasal type extranodal NK/T cell lymphoma%结外鼻型NK/T细胞淋巴瘤27例临床分析

    Institute of Scientific and Technical Information of China (English)

    李楠; 李彩霞; 刘红; 叶璐; 马超; 吴德沛

    2011-01-01

    Objective To analyze the clinical characteristic of the nasal type extranodal NK/T cell lymphoma (ENKL) as well as the therapeutic effects for different treatment methods and element that would affect prognosis.Methods Review and analyze the 27 patients with pathologically confirmed ENKL patients received radiotherapy (3 cases),chemotherapy (9 cases),combination of radiotherapy and chemotherapy (15 cases),3 of whom received auto-HSCT.Detailed B symptoms,lactate dehydrogenase (LDH),performance status (PS) scores,international prognostic index (IPI),Ann Arbor stage and therapeutic modality were included in univariate analysis.Results The average overall survival time was 32 (2-42) months.The 1,2and 3 year overall survival (OS) rates were 79.5 %,71.6 %,53.7 %,respectively.The 2-year overall survival of patients who was early stage (stage Ⅰ + Ⅱ ) was 83.3 %,and those who was advanced stage(stage Ⅲ+Ⅳ) was 62.3 % (P =0.368).Among the patients in early stage,after radiotherapy or chemotherapy,4 cases achieved OR (overall response) which is complete remission (CR) or partial remission (PR),9/10 in combination of radiotherapy and chemotherapy achieved OR. While among those in their advantage stage,the OR in chemotherapy is 2 cases,2/5 in combination of radiotherapy and chemotherapy.In univariate analysis,age and short-term response were main factors of survival (P <0.05).Conclusion To treat the nasal ENKL in the early stage,radiotherapy can achieve a better effect,while combination of radiotherapy and chemotherapy is an important method for patients in advantage stage.Age and short-term response may be.prognostic factors of nasal type ENKL.%目的 分析结外鼻型NK/T细胞淋巴瘤(ENKL)的临床特征、不同治疗方法的疗效及影响预后的因素.方法 回顾性分析27例ENKL患者,予单纯放疗3例,单纯化疗9例,其余15例采用放化疗联合治疗,其中3例患者行自体造血干细胞移植(auto-HSCT).对B组症状、乳酸脱

  10. Production of α-galactosylceramide by a prominent member of the human gut microbiota.

    Directory of Open Access Journals (Sweden)

    Laura C Wieland Brown

    2013-07-01

    Full Text Available While the human gut microbiota are suspected to produce diffusible small molecules that modulate host signaling pathways, few of these molecules have been identified. Species of Bacteroides and their relatives, which often comprise >50% of the gut community, are unusual among bacteria in that their membrane is rich in sphingolipids, a class of signaling molecules that play a key role in inducing apoptosis and modulating the host immune response. Although known for more than three decades, the full repertoire of Bacteroides sphingolipids has not been defined. Here, we use a combination of genetics and chemistry to identify the sphingolipids produced by Bacteroides fragilis NCTC 9343. We constructed a deletion mutant of BF2461, a putative serine palmitoyltransferase whose yeast homolog catalyzes the committed step in sphingolipid biosynthesis. We show that the Δ2461 mutant is sphingolipid deficient, enabling us to purify and solve the structures of three alkaline-stable lipids present in the wild-type strain but absent from the mutant. The first compound was the known sphingolipid ceramide phosphorylethanolamine, and the second was its corresponding dihydroceramide base. Unexpectedly, the third compound was the glycosphingolipid α-galactosylceramide (α-GalCer(Bf, which is structurally related to a sponge-derived sphingolipid (α-GalCer, KRN7000 that is the prototypical agonist of CD1d-restricted natural killer T (iNKT cells. We demonstrate that α-GalCer(Bf has similar immunological properties to KRN7000: it binds to CD1d and activates both mouse and human iNKT cells both in vitro and in vivo. Thus, our study reveals BF2461 as the first known member of the Bacteroides sphingolipid pathway, and it indicates that the committed steps of the Bacteroides and eukaryotic sphingolipid pathways are identical. Moreover, our data suggest that some Bacteroides sphingolipids might influence host immune homeostasis.

  11. 持续肾脏替代治疗侵袭性NK/T细胞淋巴瘤并发急性肿瘤溶解综合征1例并文献复习%Continuous renal replacement therapy on acute tumor lysis syndrome in an aggressive NK/T cell lymphoma:A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    陈芯仪; 吴俣

    2013-01-01

    Objective:To improve the recognition of acute tumor lysis syndrome (ATLS) and to explore the role of continuous renal replacement therapy (CRRT) in its emergency.Method:A case of ATLS in an aggressive NK/T cell lymphoma was emergently cured by CRRT.Result:After CRRT,the patient with heart failure symptoms quickly eased,urine output increased,potassium and metabolic acidosis were corrected promptly,and renal function improved quickly.Conclusion:ATLS patients should be considered early CRRT if efficacy of drugs is poor.In ATLS patients of unstable hemodynamics and intolerance for routine hemodialysis,CRRT should be a superior option.%目的:提高对急性肿瘤溶解综合征(ATLS)的认识和探讨持续肾脏替代治疗(CRRT)在其急救中的作用.方法:对1例侵袭性NK/T细胞淋巴瘤化疗后并发ATLS患者,采用CRRT救治.结果:通过CRRT,患者心力衰竭症状很快得到缓解,尿量增多,高钾、代谢性酸中毒及时得到纠正,肾功能也很快得到改善,疗效显著.结论:对于ATLS患者,如果药物疗效欠佳,应及早考虑CRRT;如果患者血流动力学不稳定,不能耐受普通血液透析治疗,CRRT应成为优先考虑的治疗选择.

  12. 慢性肝脏疾病中CD3~-CD161~+NK和CD3~+CD161~+NKT细胞亚群的变化研究%Alterations of CD3~- CD161~+NK cell and CD3~+CD161~+NKT Cell population in the chronic hepatic diseases

    Institute of Scientific and Technical Information of China (English)

    杨秀华; 朱文静; 王秀云; 郭存丽

    2010-01-01

    目的 探讨CD3~-CD161~+NK、CD3~+CD161~+NKT细胞在慢性肝炎/肝硬化及肝细胞癌患者肝脏组织及外周血中表达及意义.方法 利用流式细胞仪对31例肝细胞癌患者、59例慢性肝炎/肝硬化患者肝脏组织及外周血、15例正常肝脏组织、48例正常人外周血中的CD3~-CD161~+NK和CD3~+CD161~+NKT进行定量分析.结果 慢性肝炎/肝硬化组CD3~-CD161~+NK细胞[(13.4±1.3)%]和肝细胞癌癌周组CD3~-CD161~+NK细胞[(16.7±4.8)%]及远离肝癌组的肝脏组织CD3~-CD161~+NK细胞[(22.0±4.4)%]与正常肝脏组织CD3~-CD161~+NK细胞[(35.1±7.2)%]相比,肝细胞癌癌周肝脏组织内含量最低(t值分别为2.301、2.137、2.034,P<0.05);外周血中肝细胞癌组CD3~-CD161~+NK细胞[(11.6±6.3%)]、CD3~+CD161~+NKT细胞[(14.7±6.2)%]与慢性肝炎/肝硬化组CD3~-CD161~+NK细胞[(10.8±1.7)%]、CD3~+CD161~+NKT细胞[(12.5±0.8)%]、正常对照组CD3~-CD161~+NK细胞[(7.5±0.8)%]、CD3~+CD161~+NKT细胞[(13.8±1.7)%]相比肝癌组CD3~-CD161~+NKT细胞含量最高(t值分别为2.134,2.099,P<0.05),肝癌组CD3~+CD161~+NKT细胞含量最高(t值分别为2.125,2.154,P<0.05).结论 由于NK细胞及NKT细胞数量减少或/和活性降低,使肿瘤细胞逃逸了免疫监视,可能促进了肿瘤的发生、发展及转移.%Objective To investigate the significance of the alteration of NK cell population in hepatocellular carcinoma(HCC).Methods The number and distribution of CD3~-CD161~+NK cells,CD3~+CD161~+NKT cells in liver tissue(31 patients vs 15 healthy controls)and peripheral blood(59 patients vs 48 healthy controls)of chronic hepatitis/hepatic cirrhosis were analyzed by flow cytometry.Results CD3~-CD161~+NK cells[(16.7±4.8)%],in the surrounding tissue of HCC were significantly lower than far distancing hepatocellular carcinoma group[(22.0±4.4)%]、chronic hepatitis/hepatic cirhosis group[(13.4±1.3)%],and normal control group[(35.1±7.2)%](t=2.301,2.137,2.034,P<0.05).CD3~-CD161~+NK cells[(11.6±6

  13. Multifocal primary cutaneous extranodal NK/T lymphoma nasal type*

    Science.gov (United States)

    de Vasconcelos, Pedro; Ferreira, Cristina; Soares-Almeida, Luís; Filipe, Paulo

    2016-01-01

    Nasal type extranodal NK/T-cell lymphoma is a distinct entity according to the World Health Organization classification. Although 60% to 90% of patients with this disease present with a destructive mass in the midline facial tissues, it may also primarily or secondarily involve extranasal sites, like the skin. We report the case of a 77-year-old patient that came to our department with erythematous plaques of the right leg and eczematous lesions of the trunk. These lesions were biopsied and the patient was diagnosed with extranodal NK/T-cell lymphoma, nasal type. He was treated with multi-agent systemic chemotherapy but died 5 months after diagnosis. This case highlights the rarity and variability of cutaneous features of this disease and its aggressive course and poor prognosis. PMID:27192524

  14. Expression of triggering receptor on myeloid cell 1 and histocompatibility complex molecules in sepsis and major abdominal surgery

    Institute of Scientific and Technical Information of China (English)

    Nestor González-Roldán; Constantino López-Macías; Armando Isibasi; Eduardo Ferat-Osorio; Rosalía Aduna-Vicente; Isabel Wong-Baeza; Noemí Esquivel-Callejas; Horacio Astudillo-de la Vega; Patricio Sánchez-Fernández; Lourdes Arriaga-Pizano; Miguel Angel Villasís Keever

    2005-01-01

    AIM: To evaluate the surface expression of triggering receptor on myeloid cell 1 (TREM-1), class Ⅱ major histocompatibility complex molecules (HLA-DR), andthe expression of the splicing variant (svTREM-1) ofTREM-1 in septic patients and those subjected to major abdominal surgery.METHODS: Using flow cytometry, we examined the surface expression of TREM-1 and HLA-DR in peripheral blood monocytes from 11 septic patients, 7 elective gastrointestinal surgical patients, and 10 healthy volunteers. svTREM-1 levels were analyzed by RT-PCR. RESULTS: Basal expression of TREM-1 and HLA-DR in healthy volunteers was 35.91±14.75 MFI and75.8±18.3%, respectively. In septic patients, TREM-1 expression was 59.9±23.9 MFI and HLA-DR expression was 44.39±20.25%, with a significant differencebetween healthy and septic groups (P<0.05) for bothmolecules. In the surgical patients, TREM-1 and HLA-DR expressions were 56.8±20.85 MFI and 71±13.8% before surgery and 72.65±29.92 MlFI and 72.82±22.55% after surgery. TREM-1 expression was significantly different(P = 0.0087) between the samples before and aftersurgery and svTREM-1 expression was 0.8590±0.1451 MF1, 0.8820±0.1460 MF1, and 2.210±0.7873MF1 in the healthy, surgical (after surgery) and septic groups, respectively. There was a significant difference (P = 0.048) in svTREM-1 expression between the healthy and surgical groups and the septic group.CONCLUSION: TREM-1 expression is increased during systemic inflammatory conditions such as sepsis and the postoperative phase. Simultaneous low expression of HLA-DR molecules correlates with the severity of illness and increases susceptibility to infection. Additionally, TREM-1 expression is distinctly different in surgical patients at different stages of the inflammatory response before and after surgery. Thus, surface TREM-1 appears to be an endogenous signal during the course of the inflammatory response. svTREM-1 expression is significantly increased during sepsis, appearing to be

  15. Prospective Evaluation of Procalcitonin, Soluble Triggering Receptor Expressed on Myeloid Cells-1 and C-Reactive Protein in Febrile Patients with Autoimmune Diseases

    OpenAIRE

    Lin, Chou-Han; Hsieh, Song-Chou; Keng, Li-Ta; Lee, Ho-Sheng; Chang, Hou-Tai; Liao, Wei-Yu; Ho, Chao-Chi; Yu, Chong-Jen

    2016-01-01

    Background Both procalcitonin (PCT) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have been investigated separately as indicators of infection in patients with autoimmune diseases. Our study simultaneously evaluated both PCT and sTREM-1 along with C-reactive protein (CRP) in febrile patients with autoimmune diseases. Methods Fifty-nine patients were enrolled in the study. The patients were categorized into the infection group (n = 24) or the disease flare group (n = 3...

  16. Triggering receptor expressed on myeloid cells-1 and respiratory disease%髓样细胞触发受体-1与呼吸系统疾病

    Institute of Scientific and Technical Information of China (English)

    李新胜; 陈绍平

    2013-01-01

    髓样细胞触发受体-1(triggering receptor expressed on myeloid cells-1,TREM-1)是表达于中性粒细胞和单核细胞表面的膜受体,属于免疫蛋白超家族,与未知配体结合有放大炎症反应的作用.近来研究发现可溶性髓样细胞触发受体-1作为生物标记物与呼吸系统多种疾病有密切的联系.本文就TREM-1的结构、表达及其与呼吸系统疾病的关系进行综述.

  17. Serum Soluble Triggering Receptor Expressed on Myeloid Cells-1 and Procalcitonin Can Reflect Sepsis Severity and Predict Prognosis: A Prospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Zhenyu Li

    2014-01-01

    Full Text Available Objective. To investigate the prognostic significance of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1, procalcitonin (PCT, N-terminal probrain natriuretic peptide (NT-pro-BNP, C-reactive protein (CRP, cytokines, and clinical severity scores in patients with sepsis. Methods. A total of 102 patients with sepsis were divided into survival group (n=60 and nonsurvival group (n=42 based on 28-day mortality. Serum levels of biomarkers and cytokines were measured on days 1, 3, and 5 after admission to an ICU, meanwhile the acute physiology and chronic health evaluation II (APACHE II and sequential organ failure assessment (SOFA scores were calculated. Results. Serum sTREM-1, PCT, and IL-6 levels of patients in the nonsurvival group were significantly higher than those in the survival group on day 1 (P<0.01. The area under a ROC curve for the prediction of 28 day mortality was 0.792 for PCT, 0.856 for sTREM-1, 0.953 for SOFA score, and 0.923 for APACHE II score. Multivariate logistic analysis showed that serum baseline sTREM-1 PCT levels and SOFA score were the independent predictors of 28-day mortality. Serum PCT, sTREM-1, and IL-6 levels showed a decrease trend over time in the survival group (P<0.05. Serum NT-pro-BNP levels showed the predictive utility from days 3 and 5 (P<0.05. Conclusion. In summary, elevated serum sTREM-1 and PCT levels provide superior prognostic accuracy to other biomarkers. Combination of serum sTREM-1 and PCT levels and SOFA score can offer the best powerful prognostic utility for sepsis mortality.

  18. Prospective Evaluation of Procalcitonin, Soluble Triggering Receptor Expressed on Myeloid Cells-1 and C-Reactive Protein in Febrile Patients with Autoimmune Diseases

    Science.gov (United States)

    Lin, Chou-Han; Hsieh, Song-Chou; Keng, Li-Ta; Lee, Ho-Sheng; Chang, Hou-Tai; Liao, Wei-Yu; Ho, Chao-Chi; Yu, Chong-Jen

    2016-01-01

    Background Both procalcitonin (PCT) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have been investigated separately as indicators of infection in patients with autoimmune diseases. Our study simultaneously evaluated both PCT and sTREM-1 along with C-reactive protein (CRP) in febrile patients with autoimmune diseases. Methods Fifty-nine patients were enrolled in the study. The patients were categorized into the infection group (n = 24) or the disease flare group (n = 35). sTREM-1, PCT and CRP concentrations at fever onset were compared between the two groups of patients. Results sTREM-1 and CRP did not differ between the two groups. PCT [median (range), ng/ml] was higher in the infection group than in the disease flare group [0.53 (0.02–12.85) vs. 0.12 (0.02–19.23), p = 0.001]. The area under the receiver-operating characteristic (ROC) for diagnosis of infection was 0.75 for PCT (p = 0.001), 0.63 for CRP (p = 0.09) and 0.52 for sTREM-1 (p = 0.79). Using 0.2 ng/ml as the cutoff value for PCT, sensitivity was 0.75 and specificity was 0.77. Negative predictive values for PCT were 92%, 87% and 82% for a prevalence of infection of 20%, 30%, and 40%, respectively. Neither immunosuppressants nor biomodulators affected the level of the three biomarkers. However, in patients treated with corticosteroids, the levels of sTREM-1 and CRP were significantly decreased compared with the untreated patients. Conclusions Setting PCT at a lower cutoff value could provide useful information on excluding infection in febrile patients with autoimmune diseases. The possible effect of corticosteroids on the level of sTREM-1 as an infection marker deserves further study. PMID:27096761

  19. Dynamic changes of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) reflect sepsis severity and can predict prognosis: a prospective study

    Science.gov (United States)

    2011-01-01

    Background We examined the utility of serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for the diagnoses, severity assessments, and predicting the prognoses of patients with sepsis and compared sTREM-1 values with those of C-reactive protein (CRP) and procalcitonin (PCT). Methods Fifty-two patients with sepsis were included: 15 sepsis cases and 37 severe sepsis cases (severe sepsis + septic shock). Serum levels of sTREM-1, CRP, and PCT were determined on days 1, 3, 5, 7, 10, and 14 after admission to an ICU. Results Serum sTREM-1 levels of patients with severe sepsis were significantly higher than for those with sepsis on day 1 (240.6 pg/ml vs. 118.3 pg/ml; P < 0.01), but CRP and PCT levels were not significantly different between the two groups. The area under an ROC curve for sTREM-1 for severe sepsis patients was 0.823 (95% confidence interval: 0.690-0.957). Using 222.5 pg/ml of sTREM-1 as the cut-off value, the sensitivity was 59.5%, the specificity was 93.3%, the positive predictive value was 95.6%, the negative predictive value was 48.3%, the positive likelihood ratio was 8.92, and the negative likelihood ratio was 0.434. Based on 28-day survivals, sTREM-1 levels in the surviving group showed a tendency to decrease over time, while they tended to gradually increase in the non-surviving group. sTREM-1 levels in the non-surviving group were higher than those in the surviving group at all time points, whereas CRP and PCT levels showed a tendency to decrease over time in both groups. sTREM-1 levels and Sequential Organ Failure Assessment (SOFA) scores were positively correlated (r = 0.443; P < 0.001), and this correlation coefficient was greater than the correlation coefficients for both CRP and PCT. Conclusions Serum sTREM-1 levels reflected the severity of sepsis more accurately than those of CRP and PCT and were more sensitive for dynamic evaluations of sepsis prognosis. Trial Registration Current controlled trials Chi

  20. 髓系细胞触发受体1的研究进展%Research Progress on Triggering Receptor Expressed on Myeloid Cells-1

    Institute of Scientific and Technical Information of China (English)

    王坤(综述); 张建新; 党胜春(审校)

    2014-01-01

    髓系细胞触发受体1(TREM-1)主要在中性粒细胞和单核巨噬细胞中表达,能诱导中性粒细胞和单核细胞分泌肿瘤坏死因子α、白细胞介素1β等促炎因子,在炎症的级联放大反应中发挥重要作用。 TREM-1表达上调在败血症休克及其他感染中对细胞因子应答的激活起重要作用,阻断TREM-1的表达,可以减轻细菌引起的全身高炎症综合征动物模型的炎性反应,并提高存活率。该文对TREM-1的信号转导机制和天然配体进行总结,并探讨其作为分子靶点治疗疾病和作为生物标志物诊断疾病和判断预后的作用。%Triggering receptor expressed on myeloid cells-1 ( TREM-1 ) is mainly expressed on neutro-phils and monocytes/macrophages.It induces neutrophils and monocytes to increase the release of proinflam-matory factors such as TNF-α,IL-1βand INF-γ,which plays an important role in the amplification of inflam-mation.Up-regulated expression of TREM-1 appears to be a crucial step during the activation of the over-whelming cytokine response in septic shock and other infections .Blocking the expression of TREM-1 can reduce inflammation and increase survival rate in animal models of systemic hyperinflammatory syndromes caused by bacterial infections.Here is to make a review of the signaling transduction mechanisms and the nat-ural ligand of TREM-1,and make further discussion on its therapeutic values as a molecular target and diag-nostic values as a biomarker in related diseases.

  1. Primary NK/T cell lymphoma nasal type of the colon

    Directory of Open Access Journals (Sweden)

    Ana María Chirife

    2013-02-01

    Full Text Available Since nasal NK/T-cell lymphoma and NK/T-cell lymphoma nasal type are rare diseases, colonic involvement has seldom been seen. We report a case of a patient with a primary NK/T-cell lymphoma nasal type of the colon. The patient had no history of malignant diseases and was diagnosed after exhaustive study in the context of fever of unknown origin. The first therapeutic approach followed the DAEPOCH-protocol: etoposide, prednisone, doxor-rubicin, vincristine and cyclophosphamide. The persistence of constitutional symptoms after the first treatment course motivated the switch to a second line following the SMILE-protocol: dexamethasone, metotrexate, ifosfamide, E.coli L-asparaginase, and etoposide. Despite intensive chemotherapy, the patient died 2 months after the diagnose of an extranodal NK/T-cell lymphoma of the colon and 4 months after the first symptomatic appearance of disease.

  2. [Aggressive NK/T cell leukemia/lymphoma associated with EBV].

    Science.gov (United States)

    Sousa, Jamira; Cabezuelo, Lourdes; Almeida, Sérgio; Filipe, Carlos; Simão, Adélia; Carvalho, Armando; Nascimento Costa, J

    2011-12-01

    The authors describe an unusual case of a young man presenting with fever, asthenia, anorexia and jaundice, associated to hepatosplenomegaly, evolving rapidly to multiorganic failure. Final diagnosis revealed an aggressive NK cell leukemia/lymphoma associated to the Epstein-Barr virus (EBV). The diagnosis, suggested clinically and after bone marrow immunophenotyping, was confirmed by morphologic and immunohistochemical findings on the post-mortem hepatic and splenic biopsy .The tumor cells were positive for CD3 and cytotoxic molecules, TIA, granzyme B and perforin. The herein reported case is a rare clinical entity, only recently recognized and with a difficult early diagnosis. We emphasize the necessity to exclude a Natural Killer cell malignancy in cases with identical characteristics.

  3. NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

    DEFF Research Database (Denmark)

    Iversen, Marie Beck; Jensen, Simon Kok; Hansen, Anne Louise;

    2015-01-01

    that received local pre-treatment with αGalCer prior to intra-vaginal HSV-2 infection had a lower mean disease score, mortality and viral load in the vagina following infection, compared to mice that did not receive αGalCer pre-treatment. Further, we found increased numbers of CD45 and NK1.1 positive cells...

  4. Clinicoradiological changes of brain NK/T cell lymphoma manifesting pure akinesia: a case report

    Directory of Open Access Journals (Sweden)

    Shimokawa Reiko

    2011-11-01

    Full Text Available Abstract Background Pure akinesia (PA is a distinct form of parkinsonism characterized by freezing phenomena. Little is known about brain tumor-associated PA. We highlight the clinicoradiological changes in a patient with PA and central nervous system (CNS metastases of natural killer/T-cell lymphoma (NKTL. Case presentation A 68-year-old man with stage IVB extranodal NKTL developed a gait disturbance. Neurological examination of his gait revealed freezing, start hesitation, short step, forward flexion posture, festination and postural instability. Mild facial hypomimia and micrographia were observed. There was no rigidity or tremor in any of the four extremities. Brain magnetic resonance imaging (MRI displayed T2-hyperintense lesions in the dorsal brainstem, cerebellum and periventricular white matter. Diffusion-weighted imaging (DWI and the apparent diffusion coefficient (ADC revealed hyperintensity in these regions. Cerebrospinal fluid cytology revealed CD56-positive cells on immunohistochemical staining. The patient's neurological deficits did not respond to L-dopa treatment and intrathecal administration of methotrexate (MTX. Two weeks later, he displayed confusion and generalized convulsions. T2-hyperintense lesions spread to the basal ganglia and the infratentorial regions. Gadolinium enhancement was observed in the cerebellum and frontal subcortex. DWI and the ADC revealed diffusion-restricted lesions in the middle cerebellar peduncles, left internal capsules and cerebral white matter. MTX pulse therapy and intrathecal administration of cytosine arabinoside and MTX were performed. Two months later, his ambulatory state was normalized. Brain MRI also revealed marked alleviation of the infratentorial and supratentorial lesions. Conclusions The clinicoradiological profile of our patient suggested that dorsal ponto-mesencephalic lesions could contribute to the pathogenesis of PA. Physicians should pay more attention to striking CNS seeding of metastatic NKTL. MTX pulse therapy had an excellent effect in improving serious symptoms and brain lesions in our patient.

  5. Augmentation of NKT and NK cell-mediated cytotoxicity by peptidoglycan monomer linked with zinc

    Directory of Open Access Journals (Sweden)

    Ines Mrakovcic-Šutic

    2002-01-01

    Full Text Available Background: Peptidoglycan monomer (PGM, which was originally prepared by biosynthesis from culture fluids of penicillin-treated Brevibacterium divaricatum, is an immunostimulator, the activities of which might be improved by addition of zinc (Zn to the basic molecule.

  6. Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity

    OpenAIRE

    Chang, Y.J.; Kim, H. Y.; Albacker, L.A.; Lee, H H; Baumgarth, N; Akira, S; Savage, P. B.; Endo, S.; T. Yamamura; Maaskant, J.; Kitano, N.; A Singh; Bhatt, A; Besra, G S; Elzen, van den, SJ Stef

    2010-01-01

    Infection with influenza A virus represents a major public health threat worldwide, particularly in patients with asthma. However, immunity induced by influenza A virus may have beneficial effects, particularly in young children, that might protect against the later development of asthma, as suggested by the hygiene hypothesis. Herein, we show that infection of suckling mice with influenza A virus protected the mice as adults against allergen-induced airway hyperreactivity (AHR), a cardinal f...

  7. A case of rapid growing colonic NK/T cell lymphoma complicated by Crohn’s disease

    OpenAIRE

    Zheng, Shumei; Xu, Hui; Ouyang, Qin; Xue, Linyun; Zhang, Yong; Cui, Dejun

    2013-01-01

    A 37-year-old man developed abdominal pain and bloody diarrhea 11 months before admission. The colonoscopy revealed multifocal ulcers in the colon. Histology showed active chronic inflammation. Although anti-tuberculosis medication was effective, his symptoms repeated 2 months later. The subsequent colonoscopy revealed more extensive irregular ulcers than before, and he was clinically suspected with intestinal malignant lymphoma. He underwent subtotal colectomy and was histologically suggeste...

  8. Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice

    DEFF Research Database (Denmark)

    Buschard, Karsten; Hansen, Axel Jacob Kornerup; Jensen, Karen;

    2011-01-01

    Ethanol ('alcohol') is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules.......Ethanol ('alcohol') is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules....

  9. Development in research on triggering receptor expressed on myeloid cells-1 signal transduction%髓样细胞表达的触发受体-1与炎症信号转导的研究进展

    Institute of Scientific and Technical Information of China (English)

    苏龙翔; 解立新

    2012-01-01

    The triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently identified molecule involved in the cascade amplification of inflammatory response.Several microbial components can up-regulate the surface expression of TREM-1 and synergizes with the ligand of TREM-1 in activating this receptor.Activation via TREM-1 induces production of pro-inflammatory cytokices and related inflammatory responses because TREM-1 can noticeably amplify the inflammatory response in endotoxemia arisen from lipopolysaccharide (LPS).There are lots of investigations about the TREM-1 activation signal pathway that have been done and have shown some progress.Otherwise,TREM-1 synergizes with the Toll-like receptors signaling pathway in amplifying the inflammatory response mediated by LPS,but the specific mechanism is not clear enough.In this review,we will focus on the mechanism of TREM-1 signal transduction,clarifying the function of some relative signal moleculars such as TLR,DAP-12,MAPKs,NTAL,CARD9,NLRs.TREM-1 signal transduction mechanism in-depth study will further clarify the pathogenesis of sepsis and to find new therapeutic targets.%研究表明髓样细胞表达的触发受体-1(TREM-1)参与了炎性反应的级联放大过程.细菌的某些成分可以上调细胞表面TREM-1的表达,并且能和TREM-1配体协同激活TREM-1受体向下游传递信号.TREM-1被激活后会诱导前炎性因子的产生并引起相关的炎症反应.由于TREM-1是明显放大内毒素脂多糖(LPS)所引起的炎性反应的关键介质,因此对于TREM-1激活炎症信号通路的研究取得了一定的进展.然而,TREM-1在协同Toll样受体激活炎性反应的信号通路的具体机制尚未完全明晰.专注于TREM-1的信号转导,阐明与此通路相关的信号分子,如TLR、DAP-12、MAPKs、NTAL、CARD9、NLRs的作用,为进一步揭示脓毒症的发病机制并寻找新的治疗靶点.

  10. Et kritisk bidrag til en etisk seksualpædagogik tænkt med teorier af Jacques Lacan, Jean-Luc Marion og Emmanuel Lévinas

    DEFF Research Database (Denmark)

    Secher, Marianne Træbing

    2013-01-01

    kind of dilemmas which occur in the field of sexology. The help that we must provide to the mentally ill can’t just be that of concrete advice. Often the dilemmas are of a more complex nature, than that which can be solved by teaching how to masturbate, how to get a lover or the likes. In accordance...

  11. Validering av RAADS: ett självskattningsinstrument för vuxna med misstänkt autismspektrumtillstånd

    OpenAIRE

    Andersen, Lisa

    2010-01-01

    Trots vetskap om att den kliniska bilden vid autismspektrumtillstånd (AST) förändras med åldern råder det brist på diagnostiska instrument som är specifikt designade för vuxna. Ritvo Autism and Asperger Diagnostic Scale (RAADS) är en självskattningsskala utvecklad för detta syfte. Den svenska versionen av RAADS utvärderades i föreliggande studie med avseende på intern konsistens, diagnostisk validitet och samtidig validitet. Undersökningsgruppen bestod av 75 individer med högfungerande AST sa...

  12. Et kritisk bidrag til en etisk seksualpædagogik tænkt med teorier af Jacques Lacan, Jean-Luc Marion og Emmanuel Lévinas

    DEFF Research Database (Denmark)

    Secher, Marianne Træbing

    2013-01-01

    of sexology. The help that we must provide to the mentally ill can’t just be that of concrete advice. Often the dilemmas are of a more complex nature, than that which can be solved by teaching how to masturbate, how to get a lover or the likes. In accordance with these dilemmas a new ethics is proposed...

  13. [Molecular pathogenesis of peripheral T cell lymphoma (2): extranodal NK/T cell lymphoma, nasal type, adult T cell leukemia/lymphoma and enteropathy associated T cell lymphoma].

    Science.gov (United States)

    Couronné, Lucile; Bastard, Christian; Gaulard, Philippe; Hermine, Olivier; Bernard, Olivier

    2015-11-01

    Peripheral T-cell lymphomas (PTCL) belong to the group of non-Hodgkin lymphoma and particularly that of mature T /NK cells lymphoproliferative neoplasms. The 2008 WHO classification describes different PTCL entities with varying prevalence. With the exception of histologic subtype "ALK positive anaplastic large cell lymphoma", PTCL are characterized by a poor prognosis. The mechanisms underlying the pathogenesis of these lymphomas are not yet fully understood, but development of genomic high-throughput analysis techniques now allows to extensively identify the molecular abnormalities present in tumor cells. This review aims to summarize the current knowledge and recent advances about the molecular events occurring at the origin or during the natural history of main entities of PTCL. The first part published in the October issue was focused on the three more frequent entities, i.e. angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, and anaplastic large cell lymphoma. The second part presented herein will describe other subtypes less frequent and of poor prognosis : extranodal NK/T-cell lymphoma, nasal type, adult T-cell leukemia/lymphoma, and enteropathy-associated T-cell lymphoma. PMID:26576610

  14. Cell-autonomous requirement for TCF1 and LEF1 in the development of Natural Killer T cells.

    Science.gov (United States)

    Berga-Bolaños, Rosa; Zhu, Wandi S; Steinke, Farrah C; Xue, Hai-Hui; Sen, Jyoti Misra

    2015-12-01

    Natural killer T (NKT) cells develop from common CD4(+) CD8(+) thymocyte precursors. Transcriptional programs that regulate the development of NKT cells in the thymus development remain to be fully delineated. Here, we demonstrate a cell-intrinsic requirement for transcription factors TCF1 and LEF1 for the development of all subsets of NKT cells. Conditional deletion of TCF1 alone results in a substantial reduction in NKT cells. The remaining NKT cells are eliminated when TCF1 and LEF1 are both deleted. These data reveal an essential role for TCF1 and LEF1 in development of NKT cells.

  15. 可溶性髓系细胞触发受体-1在细菌性脑膜炎诊断中的意义%Value of soluble triggering receptor expressed on myeloid cells-1 in the diagnosis of bacterial meningitis

    Institute of Scientific and Technical Information of China (English)

    郭光辉; 蒋巧雅; 束振华

    2011-01-01

    Objective To investigate the value of soluble triggering receptor expressed on myeloid cells-1(sTRFM-1) in the diagnosis of bacterial meningitis. Methods The levels of sTREM-1 in cerebrospinal fluid ( CSF) were determined by quantitative FlISA assay. The serum levels of PCT and CRP were measured by using immunolumtnometrte assay and immunonephelometry method respectively. The diagnostic value of sTRFM-1 was assessed by receiver operating characteristic(ROC) curve analysis. Results The levels of CSF sTRFM-1 was significantly higher in bacterial meningitis group than in viral meningitis group and control group. There was no obvious difference in CSF sTRFM-1 between viral meningitis group and control group. According to ROC curve, when the cutoff value of CSF sTRFM-1 was set as 25 ng/L,the sensitivity and specificity of it in the diagnosis of bacterial meningitis were 90. 0% and 93. 5% ,accuracy was 93. 8 % . Conclusion Detection of CSF sTRFM-1 would have certain diagnostic value of bacterial meningitis.%目的 探讨脑脊液中可溶性髓系细胞触发受体-1(sTREM-1)在细菌性脑膜炎中的诊断意义.方法 应用定量酶联免疫吸附法(ELISA)检测脑脊液sTREM-1水平,应用免疫发光法和免疫浊度法分别检测血液中降钙素原(PCT)、C反应蛋白(CRP)水平.应用受试者工作特征 ROC 曲线研究sTREM-1的诊断效能.结果 细菌性脑膜炎组脑脊液sTREM-1 水平较病毒性脑膜炎组和对照组显著升高(P0.05).根据 ROC曲线,取sTREM-1>25 ng/L 为临界值,其曲线下面积为 0.930,诊断细菌性脑膜炎的灵敏度为 90.0%、特异度为93.5%、准确率为93.8%,诊断效能好.结论 测定脑脊液 sTREM-1 水平对于细菌性脑膜炎的诊断有一定价值.

  16. Diagnostic value of soluble form of triggering receptor expressed on myeloid cells-1(sTREM-1) in the central ;nervous system infection in infants%可溶性髓细胞触发受体-1在婴幼儿中枢神经系统感染中的诊断价值

    Institute of Scientific and Technical Information of China (English)

    王晓颖; 李莉; 李尔珍; 米荣; 康利民; 崔小岱; 呼守生

    2015-01-01

    目的:探讨可溶性髓细胞触发受体-1(soluble form of triggering receptors expressed on myeloid cell-1, sTREM-1)在小儿中枢神经系统感染中的表达及临床意义。方法选择因惊厥、颅压增高等原因收入我院的中枢神经系统感染患儿44例,年龄7 d~3岁。其中细菌性脑膜炎30例,病毒性脑炎14例,无颅内感染19例。入组患儿均于入院后3 h内行腰椎穿刺检查留取脑脊液;细菌性脑膜炎组于痊愈期复查腰穿,留取脑脊液,采用ELISA法测定脑脊液中sTREM-1水平,组间比较行秩和检验。结果细菌性脑膜炎组脑脊液中sTREM-1的水平中位数118.06(四分位间距64.21~233.23 pg/ml),病毒性脑炎组的中位数13.04(四分位间距11.17~16.96 pg/ml),无颅内感染组的中位数10.60(四分位间距9.05~12.34 pg/ml),组间比较差异有统计学意义(P0.05.5. Blood and CSF sample were collected from 10 cases. The mean level of sTREM-1 in serum and CSF in acute phase of bacterial meningitis group was(489.38 ± 466.70)pg/ml,(659.08 ± 389.44) pg/ml in serum. The correlation coefficient was 0.654, P=0.04<0.05, there was significant positive correlation. Conclu⁃sion The sTREM-1 has high expression level in serum and CSF in infantile bacterial infection. The sTREM-1 is higher in bacterial infection group than that in viral infection group and non infection group. The sTREM-1 decline following the recovery of bacterial infection. There is significant difference according to the infection severity.

  17. 髓系细胞触发受体-1在脐带血白细胞中的表达及其意义%Significance of triggering receptor expressed on myeloid cells-1 of cord blood leukocytes in neonates

    Institute of Scientific and Technical Information of China (English)

    翁晓文; 钱雷; 吕强声; 孙长虹; 周辉

    2015-01-01

    目的:观察髓系细胞触发受体-1(triggering receptor expressed on myeloid cells-1, TREM-1)在脐带血白细胞膜表达和mRNA转录水平,并分析其促进炎症细胞因子分泌的功能。方法2013年9月至2014年3月,分别收集20例健康足月新生儿出生时的脐带血和20例健康成年人的外周血,采用流式细胞术检测中性粒细胞和单核细胞TREM-1平均荧光强度和TREM-1阳性比例,实时荧光定量逆转录-聚合酶链反应技术检测白细胞TREM-1 mRNA。分别用脂多糖或LP17+脂多糖刺激脐带血白细胞,用酶联免疫吸附法检测上清液中可溶性TREM-1、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-6、IL-8浓度,并与未经刺激者(空白对照)作比较。采用成组t检验、方差分析、q检验和Pearson相关分析进行统计学分析。结果新生儿脐带血白细胞TREM-1的平均荧光强度与成年人比较,差异无统计学意义(P>0.05)。新生儿中性粒细胞TREM-1阳性百分率为(82.3±7.1)%,低于成年人的(98.6±4.8)%,差异有统计学意义(t=8.512,P<0.01)。新生儿TREM-1 mRNA水平为1.16±0.13,低于成年人的1.63±0.24,差异有统计学意义(t=7.714,P<0.01)。新生儿脐带血未经脂多糖刺激,24 h后上清液sTREM-1浓度为(34.6±6.1)pg/ml;经脂多糖刺激24 h后,上清液sTREM-1浓度上升至(156.7±36.3)pg/ml,差异有统计学意义(t=13.623,P<0.01)。LP17联合脂多糖处理后的脐带血IL-6、TNF-α、IL-8浓度明显低于仅经脂多糖处理的脐带血(P值均<0.05)。新生儿脐带血经脂多糖刺激24 h后,上清液中sTREM-1浓度与TNF-α、IL-6、IL-8浓度呈正相关(r值分别0.519、0.507和0.538,P值分别为0.019、0.022和0.014)。结论新生儿脐带血单核细胞TREM-1发育情况与成年人一致,中性粒细胞TREM-1阳性比例低于成年人

  18. Clinical value of soluble triggering receptor expressed on myeloid cells-1 in early diagnosis and prognosis of ventilator-associated pneumonia%可溶性髓系细胞触发受体-1对呼吸机相关肺炎早期诊断及预后的判断价值

    Institute of Scientific and Technical Information of China (English)

    周超; 沈美珠; 梁永杰; 李晓宁; 王秋波; 王岸; 魏丽

    2013-01-01

    目的:探讨血清及呼出气冷凝液(EVC)中可溶性髓系细胞触发受体-1(sTREM-1)对呼吸机相关性肺炎(VAP)早期诊断及预后判断的临床价值。方法对37例机械通气患者进行治疗后评估,分成非感染组13例,感染组24例(其中治疗有效组14例,治疗无效组10例),所有患者均在机械通气后第1、3、5、7天应用双抗体夹心酶联免疫吸附法(DAS-ELISA)测定血清和 EVC 中 sTREM-1水平,并记录下呼吸道分泌物细菌培养结果和患者治疗后转归;应用受试者工作特征曲线(ROC)研究 sTREM-1对 VAP 早期诊断效能及预后判断价值。结果第1天,血清及 EVC 中 sTREM-1水平治疗有效组、治疗无效组及非感染组比较,差异无统计学意义(P >0.05);第3天和第5天,感染组较非感染组有明显升高(P <0.01);第7天,治疗无效组仍处较高水平,与治疗有效组、非感染组比较差异有统计学意义(P <0.01),而治疗有效组与非感染组比较差异无统计学意义(P >0.05)。应用 ROC 分析,第3天血清和 EVC 中 sTREM-1曲线下面积分别为0.897、0.909。以第3天 EVC 中sTREM-14.70 ng/mL 为 VAP 的早期诊断界值,其诊断灵敏度为95.8%,特异度为92.3%。结论血清和 EVC 中sTREM-1检测有助于 VAP 的早期诊断,第7天血清和 EVC 中 sTREM-1水平有助于判断 VAP 的预后(撤机失败和死亡),与血清标本比较,EVC 的获得更加方便。%Objective This study examined the value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1)in serum and exhaled ventilator condensate (EVC)in early diagnosis and prognosis of ventilator-associated pneumonia (VAP). Methods A total of 37 adult patients undergoing mechanical ventilation were evaluated after treatment,including 24 patients with infection,13 without infection.Of the 24 patients with infection,10 patients were assigned

  19. Changes of soluble triggering receptor expressed on myeloid cells-1 and lactate in children with purulent meningitis%可溶性髓样细胞触发受体1、乳酸在细菌性脑膜炎患儿中的变化

    Institute of Scientific and Technical Information of China (English)

    禚志红; 郭果; 田培超; 罗强; 王怀立

    2013-01-01

    Objective To discuss the diagnosis significance of soluble triggering receptor expressed on myeloid cells-1 (STREM-1) and lactate in children with purulent meningitis,and to investigate the changes of STREM-1,lactate in cerebrospinal fluid(CSF) of purulent meningitis before and after treatment.Methods Dry chemical method and enzyme linked immunosorbent assay(ELISA) were used to measure STREM-1 and lactate levels in CSF of purulent meningitis group (24 cases),viral meningitis group (27 cases),CSF normal group (25 cases) and purulent meningitis after treatment group(22 cases).Results 1.STREM-1 and lactate levels in CSF were higher in patients with purulent meningitis than in those with viral meningitis and CSF normal group(all P < 0.05).2.STREM-1 and lactate levels in CSF were higher in patients with purulent meningitis before treatment than those after treatment(all P < 0.05).3.The area under the curve(AUC) of STREM-1 in CSF was 0.891,and at a cutoff level of 27.86 ng/L STREM-1 yielded a sensitivity of 80.8% and specificity of 75.0% ;the AUC of CSF lactate was 0.940,and at a cutoff level of 1.75 mmol/ L lactate yielded a sensitivity of 90.4% and specificity of 83.3%.Conclusions 1.STREM-1 and lactate were associated with bacterial infection,they have considerable diagnostic values in purulent meningitis.2.STREM-1 and lactate maybe worthless in differential diagnosis of purulent meningitis when treated by effective antibiotics.3.The decline of STREM-1 and lactate in CSF prompts the control of infection and good prognosis.%目的 探讨脑脊液中可溶性髓样细胞触发受体1(STREM-1)、乳酸在小儿细菌性脑膜炎鉴别诊断中的价值及其在细菌性脑膜炎治疗前后的变化.方法 采用干化学法及ELISA法分别测定24例细菌性脑膜炎、27例病毒性脑膜炎、25例脑脊液正常及22例细菌性脑膜炎患儿治疗后脑脊液中乳酸及STREM-1水平.结果 1.细菌性脑膜炎组脑脊液STREM-1、乳酸水平均高

  20. Selective Loss of Innate CD4+ Vα24 Natural Killer T Cells in Human Immunodeficiency Virus Infection

    Science.gov (United States)

    Sandberg, Johan K.; Fast, Noam M.; Palacios, Emil H.; Fennelly, Glenn; Dobroszycki, Joanna; Palumbo, Paul; Wiznia, Andrew; Grant, Robert M.; Bhardwaj, Nina; Rosenberg, Michael G.; Nixon, Douglas F.

    2002-01-01

    Vα24 natural killer T (NKT) cells are innate immune cells involved in regulation of immune tolerance, autoimmunity, and tumor immunity. However, the effect of human immunodeficiency virus type 1 (HIV-1) infection on these cells is unknown. Here, we report that the Vα24 NKT cells can be subdivided into CD4+ or CD4− subsets that differ in their expression of the homing receptors CD62L and CD11a. Furthermore, both CD4+ and CD4− NKT cells frequently express both CXCR4 and CCR5 HIV coreceptors. We find that the numbers of NKT cells are reduced in HIV-infected subjects with uncontrolled viremia and marked CD4+ T-cell depletion. The number of CD4+ NKT cells is inversely correlated with HIV load, indicating depletion of this subset. In contrast, CD4− NKT-cell numbers are unaffected in subjects with high viral loads. HIV infection experiments in vitro show preferential depletion of CD4+ NKT cells relative to regular CD4+ T cells, in particular with virus that uses the CCR5 coreceptor. Thus, HIV infection causes a selective loss of CD4+ lymph node homing (CD62L+) NKT cells, with consequent skewing of the NKT-cell compartment to a predominantly CD4− CD62L− phenotype. These data indicate that the key immunoregulatory NKT-cell compartment is compromised in HIV-1-infected patients. PMID:12097565

  1. 早期鼻腔NK/T细胞淋巴瘤三组放射治疗剂量的效果比较%Comparison of effect of three radiation doses for early stage nasal NK/T cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    吴立洲; 刘汉山; 蔡炜

    2014-01-01

    目的 探讨放疗剂量对早期鼻腔NK/T细胞淋巴瘤预后的影响.方法 将64例早期鼻腔NK/T细胞淋巴瘤患者,根据放疗剂量大小分为<50 Gy组(n=20),51 ~60 Gy组(n=24)和>60 Gy组(n=20),观察比较各组局部控制率和5年生存率.结果 经随访<50 Gy组局部控制率68.5%,5年生存率42.1%.51~60 Gy组局部控制率达到82.5%,生存率达60.9%.两组对比在局部控制率和5年生存率有统计学意义(P<0.05),但51~60 Gy组和>60 Gy组对比无统计学意义.结论 以51 ~60 Gy剂量的放疗能保证良好的局部控制率,提高患者总生存率,建议临床在选择放疗剂量时以51~60 Gy为宜.

  2. Prognostic factors and long term treatment outcome of 71 cases of nasal NK/T cell lymphoma%71例鼻腔NK/T细胞淋巴瘤放化疗效和预后因素分析

    Institute of Scientific and Technical Information of China (English)

    马辉辉; 张红雁; 钱立庭; 马军; 赵于飞; 高劲; 吴韦炜; 刘云琴

    2008-01-01

    目的 回顾性分析71例鼻腔NK/T细胞淋巴瘤患者的放化疗疗效和预后因素.方法 12年余间安徽省立医院肿瘤放疗科共收治原发鼻腔NK/T细胞淋巴瘤71例,其中男40例,女31例,年龄15~80岁,中位年龄44岁.Ann Arbor分期I E、ⅡE、ⅢE、ⅣE期分别为51、13、1、6例.单纯放疗23例,余48例放化疗.采用Kaplan-Meier法行生存分析,单因素分析用Logrank法,多因素分析用Cox比例风险模型.结果 全组死亡33例,5年总生存率为48.2%.I E、ⅡE、ⅢE+ⅣE期患者5年总生存率分别为59.0%、35.8%、0%(X2=42.61,P《0.01).单纯放疗组和放化疗组5年总生存率分别为57.9%和61.5%(X2=10.99,P>0.05).多因素回归分析表明治疗前行为状况(PS)评分、初诊时病灶超腔、近期疗效是独立预后因素.结论 放疗加CHOP方案为主的化疗未提高I E+ⅡE期患者远期生存率.治疗前PS评分、初诊时病灶超腔、近期疗效可作为判断鼻腔NK/T细胞淋巴瘤临床预后的参考指标.

  3. B cells help alloreactive T cells differentiate into memory T cells1

    OpenAIRE

    Ng, Yue-Harn; Oberbarnscheidt, Martin H.; Chandramoorthy, Harish Chinna Konda; Hoffman, Rosemary; Chalasani, Geetha

    2010-01-01

    B cells are recognized as effector cells in allograft rejection that are dependent upon T cell help to produce alloantibodies causing graft injury. It is not known if B cells can also help T cells differentiate into memory cells in the alloimmune response. We found that in B cell-deficient hosts, differentiation of alloreactive T cells into effectors was intact whereas their development into memory T cells was impaired. To test if B cell help for T cells was required for their continued diffe...

  4. K12-biotinylated Histone H4 Marks Heterochromatin in Human Lymphoblastoma Cells1

    OpenAIRE

    Camporeale, Gabriela; Oommen, Anna M; Griffin, Jacob B.; Sarath, Gautam; Zempleni, Janos

    2007-01-01

    Covalent modifications of histones play crucial roles in chromatin structure and genomic stability. Recently, we reported a novel modification of histones: biotinylation of lysine residues. Here we provide evidence that K12-biotinylated histone H4 (K12Bio H4) maps specifically to both heterochromatin (alpha satellite repeats in pericentromeric regions) and transcriptionally repressed chromatin (γ-G globin and interleukin-2) in human lymphoblastoma cells. The abundance of K12Bio H4 in these re...

  5. Multiple Tumor Types May Originate from Bone Marrow-Derived Cells1*

    OpenAIRE

    LIU, CHUNFANG; Chen, Zhongwei; Chen, Zhihong; Zhang, Tao; Lu, Yuan

    2006-01-01

    It was believed that tumors originated from the transformation of their tissue-specific stem cells. However, bone marrow-derived cells (BMDCs), which possess an unexpected degree of plasticity and often reside in other tissues, might also represent a potential source of malignancy. To study whether BMDCs play a role in the source of other tumors, BMDCs from mice were treated with 3-methycholanthrene until malignant transformation was achieved. Here we show that transformed BMDCs could form ma...

  6. Multiple Tumor Types May Originate from Bone Marrow-Derived Cells1*

    Science.gov (United States)

    Liu, Chunfang; Chen, Zhongwei; Chen, Zhihong; Zhang, Tao; Lu, Yuan

    2006-01-01

    Abstract It was believed that tumors originated from the transformation of their tissue-specific stem cells. However, bone marrow-derived cells (BMDCs), which possess an unexpected degree of plasticity and often reside in other tissues, might also represent a potential source of malignancy. To study whether BMDCs play a role in the source of other tumors, BMDCs from mice were treated with 3-methycholanthrene until malignant transformation was achieved. Here we show that transformed BMDCs could form many tumor types, including epithelial tumors, neural tumors, muscular tumors, tumors of fibroblasts, blood vessel endothelial tumors, and tumors of poor differentiation in vivo. Moreover, a single transformed BMDC has the ability to self-renew, differentiate spontaneously into various types of tumor cells in vitro, express markers associated with multipotency, and form teratoma in vivo. These data suggest that multipotent cancer stem cells seemed to originate from transformed BMDCs. Conclusively, these findings reveal that BMDCs might be a source of many tumor types, even teratoma. In addition, multipotent cancer stem cells might originate from malignant transformed BMDCs. PMID:16984729

  7. RhoC GTPase Overexpression Modulates Induction of Angiogenic Factors in Breast Cells1

    OpenAIRE

    van Golen, Kenneth L; Wu, Zhi-fen; Qiao, XiaoTan; Bao, Liwei; Merajver, Sofia D

    2000-01-01

    Inflammatory breast cancer (IBC) is a distinct and aggressive form of locally advanced breast cancer. IBC is highly angiogenic, invasive, and metastatic at its inception. Previously, we identified specific genetic alterations of IBC that contribute to this highly invasive phenotype. RhoC GTPase was overexpressed in 90% of archival IBC tumor samples, but not in stage-matched, non-IBC tumors. To study the role of RhoC GTPase in contributing to an IBC-like phenotype, we generated stable transfec...

  8. Release and fate of fluorocarbons in a shredder residue landfill cell: 1. Laboratory experiments.

    Science.gov (United States)

    Scheutz, Charlotte; Fredenslund, Anders M; Nedenskov, Jonas; Kjeldsen, Peter

    2010-11-01

    The shredder residues from automobiles, home appliances and other metal-containing products are often disposed in landfills, as recycling technologies for these materials are not common in many countries. Shredder waste contains rigid and soft foams from cushions and insulation panels blown with fluorocarbons. The objective of this study was to use laboratory experiments to estimate fluorocarbon release and attenuation processes in a monofill shredder residue (SR) landfill cell. Waste from the open SR landfill cell at the AV Miljø landfill in Denmark was sampled at three locations. The waste contained 1-3% metal and a relatively low fraction of rigid polyurethane (PUR) foam particles. The PUR waste contained less blowing agent (CFC-11) than predicted from a release model. However, CFC-11 was steadily released in an aerobic bench scale experiment. Anaerobic waste incubation bench tests showed that SRSR produced significant methane (CH(4)), but at rates that were in the low end of the range observed for municipal solid waste. Aerobic and anaerobic batch experiments showed that processes in SRSR potentially can attenuate the fluorocarbons released from the SRSR itself: CFC-11 is degraded under anaerobic conditions with the formation of degradation products, which are being degraded under CH(4) oxidation conditions prevailing in the upper layers of the SR. PMID:20435458

  9. Interaction of Sendai virus (HVJ) with chicken red blood cells, 1

    International Nuclear Information System (INIS)

    On the course of Sendai virus purification by adsorption-elution onto chicken red blood cells, it was found that the intensities of the hemagglutinating activities of each viruses were different. The cause of this differency is due to different contents of glucosamine containing high molecular substances which may situate on the surface of virions, from the results of electrophoretical and chemical analysis of the components of both adsorbed and unadsorbed viruses. (auth.)

  10. Bacterial Cellulose-Binding Domain Modulates in Vitro Elongation of Different Plant Cells1

    Science.gov (United States)

    Shpigel, Etai; Roiz, Levava; Goren, Raphael; Shoseyov, Oded

    1998-01-01

    Recombinant cellulose-binding domain (CBD) derived from the cellulolytic bacterium Clostridium cellulovorans was found to modulate the elongation of different plant cells in vitro. In peach (Prunus persica L.) pollen tubes, maximum elongation was observed at 50 μg mL−1 CBD. Pollen tube staining with calcofluor showed a loss of crystallinity in the tip zone of CBD-treated pollen tubes. At low concentrations CBD enhanced elongation of Arabidopsis roots. At high concentrations CBD dramatically inhibited root elongation in a dose-responsive manner. Maximum effect on root hair elongation was at 100 μg mL−1, whereas root elongation was inhibited at that concentration. CBD was found to compete with xyloglucan for binding to cellulose when CBD was added first to the cellulose, before the addition of xyloglucan. When Acetobacter xylinum L. was used as a model system, CBD was found to increase the rate of cellulose synthase in a dose-responsive manner, up to 5-fold compared with the control. Electron microscopy examination of the cellulose ribbons produced by A. xylinum showed that CBD treatment resulted in a splayed ribbon composed of separate fibrillar subunits, compared with a thin, uniform ribbon in the control. PMID:9701575

  11. Purification and Characterization of Abundant Secreted Protein in Suspension-Cultured Pumpkin Cells 1

    Science.gov (United States)

    Esaka, Muneharu; Enoki, Keiko; Kouchi, Bonko; Sasaki, Takuji

    1990-01-01

    The abundant secreted protein with molecular weight of 32,000 was purified from the culture medium of suspension-cultured pumpkin (Cucurbita sp.) cells. Two steps, ammonium sulfate fractionation and Sepharose 6B column chromatography, were sufficient for purification to homogeneity. Antibodies against the pure protein were used to show that a protein of the same size is made by callus cells. There is considerable homology between the amino-terminal amino acid sequence of this secreted protein and chitinase isolated from tobacco (Nicotiana tabacum L.) or bean (Phaseolus vulgaris L.). Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:16667554

  12. TCR repertoire and Foxp3 expression define functionally distinct subsets of CD4+ Treg cells1

    OpenAIRE

    Kuczma, Michal; Pawlikowska, Iwona; Kopij, Magdalena; Podolsky, Robert; Rempala, Grzegorz A.; Kraj, Piotr

    2009-01-01

    Despite extensive research efforts to characterize peripheral regulatory T cells (Treg) expressing transcription factor Foxp3, their subset complexity, phenotypic characteristics, TCR repertoire and antigen specificities remain ambiguous. Here, we identify and define two subsets of peripheral Treg cells differing in Foxp3 expression level and TCR repertoires. Treg cells expressing a high level of Foxp3 and TCRs not utilized by naive CD4+ T cells present a stable suppressor phenotype and domin...

  13. Elemental maps in human allantochorial placental vessels cells: 1. High K + and acetylcholine effects

    Science.gov (United States)

    Michelet-Habchi, C.; Barberet, Ph.; Dutta, R. K.; Guiet-Bara, A.; Bara, M.; Moretto, Ph.

    2003-09-01

    Regulation of vascular tone in the fetal extracorporeal circulation most likely depends on circulating hormones, local paracrine mechanisms and changes in membrane potential of vascular smooth muscle cells (VSMCs) and of vascular endothelial cells (VECs). The membrane potential is a function of the physiological activities of ionic channels (particularly, K + and Ca 2+ channels in these cells). These channels regulate the ionic distribution into these cells. Micro-particle induced X-ray emission (PIXE) analysis was applied to determine the ionic composition of VSMC and of VEC in the placental human allantochorial vessels in a physiological survival medium (Hanks' solution) modified by the addition of acetylcholine (ACh: which opens the calcium-sensitive K + channels, K Ca) and of high concentration of K + (which blocks the voltage-sensitive K + channels, K df). In VSMC (media layer), the addition of ACh induced no modification of the Na, K, Cl, P, S, Mg and Ca concentrations and high K + medium increased significantly the Cl and K concentrations, the other ion concentrations remaining constant. In endothelium (VEC), ACh addition implicated a significant increase of Na and K concentration, and high K + medium, a significant increase in Cl and K concentration. These results indicated the importance of K df, K Ca and K ATP channels in the regulation of K + intracellular distribution in VSMC and VEC and the possible intervention of a Na-K-2Cl cotransport and corroborated the previous electrophysiological data.

  14. Elemental maps in human allantochorial placental vessels cells: 1. High K+ and acetylcholine effects

    International Nuclear Information System (INIS)

    Regulation of vascular tone in the fetal extracorporeal circulation most likely depends on circulating hormones, local paracrine mechanisms and changes in membrane potential of vascular smooth muscle cells (VSMCs) and of vascular endothelial cells (VECs). The membrane potential is a function of the physiological activities of ionic channels (particularly, K+ and Ca2+ channels in these cells). These channels regulate the ionic distribution into these cells. Micro-particle induced X-ray emission (PIXE) analysis was applied to determine the ionic composition of VSMC and of VEC in the placental human allantochorial vessels in a physiological survival medium (Hanks' solution) modified by the addition of acetylcholine (ACh: which opens the calcium-sensitive K+ channels, KCa) and of high concentration of K+ (which blocks the voltage-sensitive K+ channels, Kdf). In VSMC (media layer), the addition of ACh induced no modification of the Na, K, Cl, P, S, Mg and Ca concentrations and high K+ medium increased significantly the Cl and K concentrations, the other ion concentrations remaining constant. In endothelium (VEC), ACh addition implicated a significant increase of Na and K concentration, and high K+ medium, a significant increase in Cl and K concentration. These results indicated the importance of Kdf, KCa and KATP channels in the regulation of K+ intracellular distribution in VSMC and VEC and the possible intervention of a Na-K-2Cl cotransport and corroborated the previous electrophysiological data

  15. Light-Affected Ca2+ Fluxes in Protoplasts from Vallisneria Mesophyll Cells 1

    Science.gov (United States)

    Takagi, Shingo; Nagai, Reiko

    1988-01-01

    In Vallisneria gigantea Graebner mesophyll cells, red light irradiation induces cytoplasmic streaming by decreasing the Ca2+ concentration in the cytoplasm, while far-red light irradiation inhibits it by increasing the concentration (S Takagi, R Nagai 1985 Plant Cell Physiol 26: 941-951). To examine the effects of light irradiation on Ca2+ fluxes across the cell membrane, protoplasts are isolated from the mesophyll cells. Changes in Ca2+ concentration in a solution bathing the protoplasts are monitored by spectrophotometry, using the Ca2+ -sensitive dye murexide. Red light irradiation induces an increase in Ca2+ concentration, which means an efflux of Ca2+ from the protoplasts. Subsequent far-red light irradiation produces a rapid decrease in Ca2+ concentration down to the dark control level; however, this is not observed in the presence of the Ca2+ -channel blocker nifedipine. Vanadate inhibits both the streaming and the Ca2+ efflux induced by red light irradiation. The results suggest that red light and far-red light control Ca2+ movements across the cell membrane, which in turn regulate the streaming. Images Fig. 1 PMID:16666272

  16. IL-6 Promotes Cardiac Graft Rejection Mediated by CD4+ Cells1

    OpenAIRE

    Booth, Adam Jared; Grabauskiene, Svetlana; Wood, Sherri Chan; Lu, Guanyi; Burrell, Bryna E.; Bishop, D. Keith

    2011-01-01

    IL-6 mediates numerous immunologic effects relevant to transplant rejection; however its specific contributions to these processes are not fully understood. To this end, we neutralized IL-6 in settings of acute cardiac allograft rejection associated with either CD8+ or CD4+ cell dominant responses. In a setting of CD8+ cell dominant graft rejection, IL-6 neutralization delayed the onset of acute rejection while decreasing graft infiltrate and inverting anti-graft Th1/Th2 priming dominance in ...

  17. Expression of soluble triggering receptor expression on myeloid cells-1 in pleural effusion

    Institute of Scientific and Technical Information of China (English)

    HUANG Lu-ying; SHI Huan-zhong; LIANG Qiu-li; WU Yan-bin; QIN Xue-jun; CHEN Yi-qiang

    2008-01-01

    Background Tdggedng receptors expressed on myeloid cells(TREM)proteins are a family of cell surface receptors expressed broadly by cells of the myeloid lineage.The aim of this study was to investigate the clinical significance of soluble TREM-1(sTREM-1)in pleural effusions,and to determine the effects of pneumonia on pleural sTREM-1 concentrations.Methods PleuraI fluid was collected from 109 patients who presented to the respiratory institute (35 with malignant pleural effusion,31 with tuberculous pleural effusion,21 with bacteriaI pleural effusion,and 22 with transudate).The concentrations of sTREM-1,tumor necrosis factor-o(TNF-α)and interleukin-1β(IL-1β)were determined jn effusion and serum samples by enzyme Iinked immunosorbent assay(ELISA).Results The concentrations of sTREM-1 in bacterial pleural effusion were significantly higher than those in malignant.tuberculous,and transudative groups(all P<0.001).An sTREM-1 cutoff value of 768.1 ng/L had a sensitivity of 86%and a specificity of 93%.Pleural sTREM-1 Ievels were positively correlated with Ievels of TNF-α and IL-1β.Patients with complicating bacterial pneumonia did not have elevated concentration of STREM-1 jn pleural effusion when compared with patients without pneumonia.Conclusions Determination of pleural sTREM-1 may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies.The occurrence of bacterial pneumonia did not affect pleural sTREM-1 concentrations.

  18. Innate immune control of EBV-infected B cells by invariant natural killer T cells.

    Science.gov (United States)

    Chung, Brian K; Tsai, Kevin; Allan, Lenka L; Zheng, Dong Jun; Nie, Johnny C; Biggs, Catherine M; Hasan, Mohammad R; Kozak, Frederick K; van den Elzen, Peter; Priatel, John J; Tan, Rusung

    2013-10-10

    Individuals with X-linked lymphoproliferative disease lack invariant natural killer T (iNKT) cells and are exquisitely susceptible to Epstein-Barr virus (EBV) infection. To determine whether iNKT cells recognize or regulate EBV, resting B cells were infected with EBV in the presence or absence of iNKT cells. The depletion of iNKT cells increased both viral titers and the frequency of EBV-infected B cells. However, EBV-infected B cells rapidly lost expression of the iNKT cell receptor ligand CD1d, abrogating iNKT cell recognition. To determine whether induced CD1d expression could restore iNKT recognition in EBV-infected cells, lymphoblastoid cell lines (LCL) were treated with AM580, a synthetic retinoic acid receptor-α agonist that upregulates CD1d expression via the nuclear protein, lymphoid enhancer-binding factor 1 (LEF-1). AM580 significantly reduced LEF-1 association at the CD1d promoter region, induced CD1d expression on LCL, and restored iNKT recognition of LCL. CD1d-expressing LCL elicited interferon γ secretion and cytotoxicity by iNKT cells even in the absence of exogenous antigen, suggesting an endogenous iNKT antigen is expressed during EBV infection. These data indicate that iNKT cells may be important for early, innate control of B cell infection by EBV and that downregulation of CD1d may allow EBV to circumvent iNKT cell-mediated immune recognition.

  19. The in vitro proliferation and cytokine production of Vα24+Vβ11+natural killer T cells in patients with systemic lupus erythematosus

    Institute of Scientific and Technical Information of China (English)

    YU Xue-man; WANG Xiao-fei

    2011-01-01

    Background Activation in vitro of natural killer T (NKT) cells in systemic lupus erythematosus (SLE) with α-galactosylceramide (α-GalCer) and dendritic cells (DC) may affect the immunoregulatory role of NKT cells. This study was designed to compare the number of NKT cells in patients with SLE to the number in healthy volunteers and measure the cytokines secreted from these NKT cells in vitro.Methods Three sets of culture conditions using (i) α-GalCer, (ii) DC, or (iii) both α-GalCer and DC (α-GalCer+DC) were adopted to expand NKT cells from peripheral blood mononuclear cells (PBMC) of patients with SLE and healthy volunteers. Flow cytometry was used to assess the levels of interleukin (IL)-4, IL-10, interferon (IFN)-y and tumor necrosis factor (TNF)-α produced by the Vα24+Vβ11+ NKT cells.Results After 14 days in culture, the total cell count and percentage of Vα24+Vβ11+ NKT cells were increased under all conditions but were highest in the α-GalCer+DC group. The level of IL-4 and IL-10 secreted by Vα24+Vβ11+ NKT cells from patients with active SLE was found to be higher than that of inactive patients and the control group (P <0.05), while the levels of IFN-y and TNF-α were lower than those found in the inactive and control groups (P <0.05).Conclusions Vα24+Vβ11+ NKT cells showed the greatest expansion in vitro with α-GalCer and DC. Th2-type cytokines from Vα24+Vβ11+ NKT cells are the predominant type in patients with SLE, while Th1 cytokines predominate in the control group. This evolution of NKT cell function during the progression of the disease may have important implications in understanding the mechanism of SLE and for the development of possible therapies using NKT cell agonists.

  20. Genetic engineering of hematopoietic stem cells to generate invariant natural killer T cells.

    Science.gov (United States)

    Smith, Drake J; Liu, Siyuan; Ji, Sunjong; Li, Bo; McLaughlin, Jami; Cheng, Donghui; Witte, Owen N; Yang, Lili

    2015-02-01

    Invariant natural killer T (iNKT) cells comprise a small population of αβ T lymphocytes. They bridge the innate and adaptive immune systems and mediate strong and rapid responses to many diseases, including cancer, infections, allergies, and autoimmunity. However, the study of iNKT cell biology and the therapeutic applications of these cells are greatly limited by their small numbers in vivo (∼0.01-1% in mouse and human blood). Here, we report a new method to generate large numbers of iNKT cells in mice through T-cell receptor (TCR) gene engineering of hematopoietic stem cells (HSCs). We showed that iNKT TCR-engineered HSCs could generate a clonal population of iNKT cells. These HSC-engineered iNKT cells displayed the typical iNKT cell phenotype and functionality. They followed a two-stage developmental path, first in thymus and then in the periphery, resembling that of endogenous iNKT cells. When tested in a mouse melanoma lung metastasis model, the HSC-engineered iNKT cells effectively protected mice from tumor metastasis. This method provides a powerful and high-throughput tool to investigate the in vivo development and functionality of clonal iNKT cells in mice. More importantly, this method takes advantage of the self-renewal and longevity of HSCs to generate a long-term supply of engineered iNKT cells, thus opening up a new avenue for iNKT cell-based immunotherapy.

  1. 血清和呼出气冷凝液中可溶性髓系细胞触发受体-1检测有助于呼吸机相关性肺炎早期诊断及预后判断%Examination of soluble triggering receptor expressed on myeloid cell-1 in serum and exhaled ventilator condensate can be taken as a marker to predict diagnosis and prognosis in patients with ventilator-associated pneumonia

    Institute of Scientific and Technical Information of China (English)

    沈美珠; 周超; 薛菲; 李晓宁; 王秋波; 陈昊; 王岸; 魏丽; 梁永杰

    2015-01-01

    目的 探讨血清及呼出气冷凝液(EVC)中可溶性髓系细胞触发受体-1(sTREM-1)对呼吸机相关性肺炎(VAP)早期诊断及预后判断的临床价值.方法 对54例机械通气患者进行治疗后评估,分成2组:非VAP组18例,VAP组36例(其中治疗有效组20例,治疗无效组16例),所有患者均在机械通气后第1、3、5、7天应用双抗体夹心酶联免疫吸附法测定血清和EVC中sTREM-1、降钙素原(PCT)水平,应用受试者工作特征(ROC)曲线研究sTREM-1、PCT等指标对VAP早期诊断效能及预后判断价值.结果 第3天和第5天,VAP组血清及EVC中sTREM-1较非VAP组有明显升高(P<0.01);第7天,血清及EVC中sTREM-1在治疗无效组仍处较高水平,与治疗有效组、非VAP组比较差异有统计学意义(P<0.01).在VAP组,血清PCT水平在第5天有明显升高(P<0.05);第7天,与治疗有效组和非VAP组比较,治疗无效组血清PCT水平仍持续升高(P<0.01);而EVC中PCT浓度仅在第7天治疗无效组患者中处于较高水平,与非VAP组、治疗有效组比较,差异有统计学意义(P<0.01).应用ROC分析,以第3天EVC中sTREM-1 4.02 μg/L为VAP的早期诊断界值,其敏感度为86.1%,特异度为66.7%,阳性预测值为83.8%,阴性预测值为70.6%(95% CI:0.631~0.979).结论 第3天血清和EVC中sTREM-1检测有助于VAP的早期诊断,第7天血清和EVC中sTREM-1、PCT水平有助于判断VAP的预后(撤机失败和死亡).与血清标本比较,EVC的获得更加方便.%Objective To discuss the value of soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) in serum and exhaled ventilator condensate (EVC) to diagnose ventilator-associated pneumonia(VAP)and predict the prognosis.Methods 54 adult patients with mechanical ventilation were valuated after treatment.54 cases were divided into two groups:36 patients in infection group,18 cases in non-infection group.The 36 patients with infection included 16 cases in ineffective subgroup and

  2. Inflammatory mechanisms in sepsis: elevated invariant natural killer T-cell numbers in mouse and their modulatory effect on macrophage function.

    Science.gov (United States)

    Heffernan, Daithi S; Monaghan, Sean F; Thakkar, Rajan K; Tran, Mai L; Chung, Chun-Shiang; Gregory, Stephen H; Cioffi, William G; Ayala, Alfred

    2013-08-01

    Invariant natural killer T cells (iNKT) cells are emerging as key mediators of innate immune cellular and inflammatory responses to sepsis and peritonitis. Invariant natural killer T cells mediate survival following murine septic shock. Macrophages are pivotal to survival following sepsis. Invariant natural killer T cells have been shown to modulate various mediators of the innate immune system, including macrophages. We demonstrate sepsis-inducing iNKT-cell exodus from the liver appearing in the peritoneal cavity, the source of the sepsis. This migration was affected by programmed death receptor 1. Programmed death receptor 1 is an inhibitory immune receptor, reported as ubiquitously expressed at low levels on iNKT cells. Programmed death receptor 1 has been associated with markers of human critical illness. Programmed death receptor 1-deficient iNKT cells failed to demonstrate similar migration. To the extent that iNKT cells affected peritoneal macrophage function, we assessed peritoneal macrophages' ability to phagocytose bacteria. Invariant natural killer T(-/-) mice displayed dysfunctional macrophage phagocytosis and altered peritoneal bacterial load. This dysfunction was reversed when peritoneal macrophages from iNKT(-/-) mice were cocultured with wild-type iNKT cells. Together, our results indicate that sepsis induces liver iNKT-cell exodus into the peritoneal cavity mediated by programmed death receptor 1, and these peritoneal iNKT cells appear critical to regulation of peritoneal macrophage phagocytic function. Invariant natural killer T cells offer therapeutic targets for modulating immune responses and detrimental effects of sepsis.

  3. Recognition of lyso-phospholipids by human natural killer T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Lisa M Fox

    2009-10-01

    Full Text Available Natural killer T (NKT cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC. Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology.

  4. Natural killer T cells in adipose tissue are activated in lean mice.

    Science.gov (United States)

    Kondo, Taisuke; Toyoshima, Yujiro; Ishii, Yoshiyuki; Kyuwa, Shigeru

    2013-01-01

    Adipose tissues are closely connected with the immune system. It has been suggested that metabolic syndromes such as type 2 diabetes, arteriosclerosis and liver steatosis can be attributed to adipose tissue inflammation characterized by macrophage infiltration. To understand a physiological and pathological role of natural killer T (NKT) cells on inflammation in adipose tissue, we characterized a subset of NKT cells in abdominal and subcutaneous adipose tissues in C57BL/6J mice fed normal or high-fat diets. NKT cells comprised a larger portion of lymphocytes in adipose tissues compared with the spleen and peripheral blood, with epididymal adipose tissue having the highest number of NKT cells. Furthermore, some NKT cells in adipose tissues expressed higher levels of CD69 and intracellular interferon-γ, whereas the Vβ repertoires of NKT cells in adipose tissues were similar to other cells. In obese mice fed a high-fat diet, adipose tissue inflammation had little effect on the Vβ repertoire of NKT cells in epididymal adipose tissues. We speculate that the NKT cells in adipose tissues may form an equivalent subset in other tissues and that these subsets are likely to participate in adipose tissue inflammation. Additionally, the high expression level of CD69 and intracellular IFN-γ raises the possibility that NKT cells in adipose tissue may be stimulated by some physiological mechanism.

  5. Hverdagsdesign

    DEFF Research Database (Denmark)

    Dickson, Thomas

    2000-01-01

    Det bedste design finder man, når ganske almindelige hverdagsting formes med gennemtænkt omhu. Desværre sker det ikke så tit.......Det bedste design finder man, når ganske almindelige hverdagsting formes med gennemtænkt omhu. Desværre sker det ikke så tit....

  6. In vitro expanded human invariant natural killer T-cells promote functional activity of natural killer cells.

    NARCIS (Netherlands)

    Moreno, M.; Molling, J.W.; Mensdorff-Pouilly, S von; Verheijen, R.H.; Blomberg, B.M.E. von; Eertwegh, A.J. van den; Scheper, R.J.; Bontkes, H.J.

    2008-01-01

    Invariant natural killer T (iNKT) cells play a pivotal role in cancer immunity through trans-activation of effector cells via swift cytokine secretion. In mice, iNKT cell activation by alpha-galactosylceramide (alpha-GC) induces potent NK cell-mediated anti-tumour effects. Here we investigated wheth

  7. Cigarette smoke alters the invariant natural killer T cell function and may inhibit anti-tumor responses.

    LENUS (Irish Health Repository)

    Hogan, Andrew E

    2011-09-01

    Invariant natural killer T (iNKT) cells are a minor subset of human T cells which express the invariant T cell receptor Vα24 Jα18 and recognize glycolipids presented on CD1d. Invariant NKT cells are important immune regulators and can initiate anti-tumor responses through early potent cytokine production. Studies show that iNKT cells are defective in certain cancers. Cigarette smoke contains many carcinogens and is implicated directly and indirectly in many cancers. We investigated the effects of cigarette smoke on the circulating iNKT cell number and function. We found that the iNKT cell frequency is significantly reduced in cigarette smoking subjects. Invariant NKT cells exposed to cigarette smoke extract (CSE) showed significant defects in cytokine production and the ability to kill target cells. CSE inhibits the upregulation of CD107 but not CD69 or CD56 on iNKT cells. These findings suggest that CSE has a specific effect on iNKT cell anti-tumor responses, which may contribute to the role of smoking in the development of cancer.

  8. Cord blood Vα24-Vβ11 natural killer T cells display a Th2-chemokine receptor profile and cytokine responses.

    Directory of Open Access Journals (Sweden)

    Susanne Harner

    Full Text Available BACKGROUND: The fetal immune system is characterized by a Th2 bias but it is unclear how the Th2 predominance is established. Natural killer T (NKT cells are a rare subset of T cells with immune regulatory functions and are already activated in utero. To test the hypothesis that NKT cells are part of the regulatory network that sets the fetal Th2 predominance, percentages of Vα24(+Vβ11(+ NKT cells expressing Th1/Th2-related chemokine receptors (CKR were assessed in cord blood. Furthermore, IL-4 and IFN-γ secreting NKT cells were quantified within the single CKR(+ subsets. RESULTS: Cord blood NKT cells expressed the Th2-related CCR4 and CCR8 at significantly higher frequencies compared to peripheral blood NKT cells from adults, while CXCR3(+ and CCR5(+ cord blood NKT cells (Th1-related were present at lower percentages. Within CD4(negCD8(neg (DN NKT cells, the frequency of IL-4 producing NKT cells was significantly higher in cord blood, while frequencies of IFN-γ secreting DN NKT cells tended to be lower. A further subanalysis showed that the higher percentage of IL-4 secreting DN NKT cells was restricted to CCR3(+, CCR4(+, CCR5(+, CCR6(+, CCR7(+, CCR8(+ and CXCR4(+ DN subsets in cord blood. This resulted in significantly decreased IFN-γ /IL-4 ratios of CCR3(+, CCR6(+ and CCR8(+ cord blood DN NKT cells. Sequencing of VA24AJ18 T cell receptor (TCR transcripts in sorted cord blood Vα24Vβ11 cells confirmed the invariant TCR alpha-chain ruling out the possibility that these cells represent an unusual subset of conventional T cells. CONCLUSIONS: Despite the heterogeneity of cord blood NKT cells, we observed a clear Th2-bias at the phenotypic and functional level which was mainly found in the DN subset. Therefore, we speculate that NKT cells are important for the initiation and control of the fetal Th2 environment which is needed to maintain tolerance towards self-antigens as well as non-inherited maternal antigens.

  9. Synthesis and evaluation of immunostimulant plasmalogen lysophosphatidylethanolamine and analogues for natural killer T cells.

    Science.gov (United States)

    Ni, Guanghui; Li, Zhiyuan; Liang, Kangjiang; Wu, Ting; De Libero, Gennaro; Xia, Chengfeng

    2014-06-01

    Plasmalogen lysophosphatidylethanolamine (pLPE) had been identified as a self antigen for natural killer T cells (NKT cells). It is very important in the development, maturation and activation of NKT cells in thymus. Besides, pLPE is a novel type of antigen for NKT cells. To evaluate the structure-activity relationship (SAR) of this new antigen, pLPE and its analogues referred to different aliphatic chains and linkages at the sn-1 position of the glycerol backbone were synthesized, and the biological activities of these analogues was characterized. It is discovered that the linkages between phosphate and lipid moiety are not important for the antigens' activities. The pLPE analogues 1, 3, 4, 7 and 9, which have additional double bonds on lipid parts, were identified as new NKT agonists. Moreover, the analogues 4, 7 and 9 were discovered as potent Th2 activators for NKT cells.

  10. The Industrial Chemical Bisphenol A (BPA) Interferes with Proliferative Activity and Development of Steroidogenic Capacity in Rat Leydig Cells1

    Science.gov (United States)

    Nanjappa, Manjunatha K.; Simon, Liz; Akingbemi, Benson T.

    2012-01-01

    ABSTRACT The presence of bisphenol A (BPA) in consumer products has raised concerns about potential adverse effects on reproductive health. Testicular Leydig cells are the predominant source of the male sex steroid hormone testosterone, which supports the male phenotype. The present report describes the effects of developmental exposure of male rats to BPA by gavage of pregnant and lactating Long-Evans dams at 2.5 and 25 μg/kg body weight from Gestational Day 12 to Day 21 postpartum. This exposure paradigm stimulated Leydig cell division in the prepubertal period and increased Leydig cell numbers in the testes of adult male rats at 90 days. Observations from in vitro experiments confirmed that BPA acts directly as a mitogen in Leydig cells. However, BPA-induced proliferative activity in vivo is possibly mediated by several factors, such as 1) protein kinases (e.g., mitogen-activated protein kinases or MAPK), 2) growth factor receptors (e.g., insulin-like growth factor 1 receptor-beta and epidermal growth factor receptors), and 3) the Sertoli cell-secreted anti-Mullerian hormone (also called Mullerian inhibiting substance). On the other hand, BPA suppressed protein expression of the luteinizing hormone receptor (LHCGR) and the 17beta-hydroxysteroid dehydrogenase enzyme (HSD17B3), thereby decreasing androgen secretion by Leydig cells. We interpret these findings to mean that the likely impact of deficits in androgen secretion on serum androgen levels following developmental exposure to BPA is alleviated by increased Leydig cell numbers. Nevertheless, the present results reinforce the view that BPA causes biological effects at environmentally relevant exposure levels and its presence in consumer products potentially has implication for public health. PMID:22302688

  11. Mesenchymal stem cell 1 (MSC1-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Ruth S Waterman

    Full Text Available BACKGROUND: Currently, there are many promising clinical trials using mesenchymal stem cells (MSCs in cell-based therapies of numerous diseases. Increasingly, however, there is a concern over the use of MSCs because they home to tumors and can support tumor growth and metastasis. For instance, we established that MSCs in the ovarian tumor microenvironment promoted tumor growth and favored angiogenesis. In parallel studies, we also developed a new approach to induce the conventional mixed pool of MSCs into two uniform but distinct phenotypes we termed MSC1 and MSC2. METHODOLOGY/PRINCIPAL FINDINGS: Here we tested the in vitro and in vivo stability of MSC1 and MSC2 phenotypes as well as their effects on tumor growth and spread. In vitro co-culture of MSC1 with various cancer cells diminished growth in colony forming units and tumor spheroid assays, while conventional MSCs or MSC2 co-culture had the opposite effect in these assays. Co-culture of MSC1 and cancer cells also distinctly affected their migration and invasion potential when compared to MSCs or MSC2 treated samples. The expression of bioactive molecules also differed dramatically among these samples. MSC1-based treatment of established tumors in an immune competent model attenuated tumor growth and metastasis in contrast to MSCs- and MSC2-treated animals in which tumor growth and spread was increased. Also, in contrast to these groups, MSC1-therapy led to less ascites accumulation, increased CD45+leukocytes, decreased collagen deposition, and mast cell degranulation. CONCLUSION/SIGNIFICANCE: These observations indicate that the MSC1 and MSC2 phenotypes may be convenient tools for the discovery of critical components of the tumor stroma. The continued investigation of these cells may help ensure that cell based-therapy is used safely and effectively in human disease.

  12. Memory-Like CD8+ T Cells Generated during Homeostatic Proliferation Defer to Antigen-Experienced Memory Cells1

    OpenAIRE

    Cheung, Kitty P.; Yang, Edward; Goldrath, Ananda W

    2009-01-01

    Naive T cells proliferate in response to lymphopenia and acquire the phenotypic and functional qualities of memory T cells, providing enhanced protection against infection. How well memory-like T cells generated during lymphopenia-induced homeostatic proliferation (HP)-memory differentiate into secondary memory cells and compete with Ag-experienced true-memory cells is unknown. We found that CD8+ HP-memory T cells generated robust responses upon infection and produced a secondary memory popul...

  13. Adenovirus viral interleukin-10 inhibits adhesion molecule expressions induced by hypoxia/reoxygenation in cerebrovascular endothelial cells1

    Institute of Scientific and Technical Information of China (English)

    Hui KANG; Peng-yuan YANG; Yao-cheng RUI

    2008-01-01

    Aim: To investigate the effects of recombinant adenovirus encoding viral interleukin-10 (vIL-10), a potent anti-inflammatory cytokine, on adhesion mol-ecule expressions and the adhesion rates of leukocytes to endothelial cells in cerebrovascular endothelial cells injured by hypoxia/reoxygenation (H/R). Methods: A recombinant adenovirus expressing vIL-10 (Ad/vIL-10 (or the green fluorescent protein (Ad/GFP) gene was constructed. A cerebrovascular endothe-lial cell line bend.3 was pretreated with a different multiplicity of infection (MOI) of Ad/vIL-10 or Ad/GFP and then exposed to hypoxia for 9 h followed by reoxygenation for 12 h. The culture supernatants were tested for the expression of vIL-10 and endogenous murine IL-10 (mIL-10) by ELISA. The effects of Ad/vIL-10 on monocyte-endothelial cell adhesion were represented as the adhesion rate. Subsequently, the expressions of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1(VCAM-1) in the endothelial cells after treat-ment with Ad/vIL-10 and H/R were analyzed by Western blotting and real-time PCR. Results: vIL-10 was expressed in cultured bEnd.3 after Ad/vIL-10 transfec-tion and was significantly increased by H/R. Ad/vIL-10 or Ad/GFP did not affect the mlL-10 level. H/R increased the mIL-10 expression, but insignificantly. Mono-cyte-endothelial cell adhesion induced by H/R was significantly inhibited by pretreatment with Ad/vIL-10 (MOI: 80). ICAM-I, and VCAM-1 in bEnd.3 and were significantly increased after H/R, while pretreatment with Ad/vIL-10 (MOI: 80) significantly inhibited their expressions. Ad/GFP did not markedly affect mono-cyte-endothelial adhesion and the expressions of ICAM-1 and VCAM-1 induced by H/R. Conclusion: Ad/vIL-10 significantly inhibits the upregulation of endot-helial adhesion molecule expressions and the increase of adhesion of monocytes-endothelial cells induced by H/R, indicating that vIL-10 gene transfer is of far-reaching significance in the therapy of cerebrovascular inflammatory diseases, and anti-adhesion treatment may reduce H/R injury.

  14. Cellular and Molecular Consequences of Peroxisome Proliferator-Activated Receptor-γ Activation in Ovarian Cancer Cells1*

    OpenAIRE

    Vignati, Sara; Albertini, Veronica; Rinaldi, Andrea; Kwee, Ivo; RIVA Cristina; Oldrini, Rita; Capella, Carlo; Bertoni, Francesco; Carbone, Giuseppina M; Catapano, Carlo V.

    2006-01-01

    Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-activated transcription factor. In addition to its canonical role in lipid and glucose metabolism, PPAR-γ controls cell proliferation, death, and differentiation in several tissues. Here we have examined the expression of PPAR-γ in ovarian tumors and the cellular and molecular consequences of its activation in ovarian cancer cells. PPAR-γ was expressed in a large number of epithelial ovarian tumors and cell lines. The PPAR-γ li...

  15. Cooperative Regulation of Cytoplasmic Streaming and Ca2+ Fluxes by Pfr and Photosynthesis in Vallisneria Mesophyll Cells 1

    Science.gov (United States)

    Takagi, Shingo; Yamamoto, Kotaro T.; Furuya, Masaki; Nagai, Reiko

    1990-01-01

    In mesophyll cells of Vallisneria gigantea Graebner, Ca2+ regulates the induction and cessation of cytoplasmic streaming. Streaming is induced when the level of calcium in the cytoplasm is lowered through light-accelerated release of Ca2+ from the cells (S Takagi, R Nagai [1988] Plant Physiol 88: 228-232). We have now initiated an investigation on the nature of the photoreceptor(s) that are involved in the regulation of Ca2+ movements across the cell membrane and of streaming. Streaming is induced only when phytochrome exists in the phytochrome—far redabsorbing form (Pfr)—and photosynthesis is allowed to take place for at least 4 minutes. The former effect is typically photoreversible by red and far-red light, and phytochrome is spectro-photometrically detectable in the crude extract from the leaves. The latter effect is assessed in terms of the wavelength dependency and the effects of diuron and atrazine, two inhibitors of photosynthesis. A similar requirement for Pfr and photosynthesis is found to be associated with the acceleration of Ca2+ efflux in the protoplasts. The results suggest that phytochrome and photosynthetic pigment(s) cooperatively regulate cytoplasmic streaming via modulation of the Ca2+ transport in the cell membrane. PMID:16667905

  16. The Transmembrane E3 Ligase GRAIL Ubiquitinates and Degrades CD83 on CD4 T Cells1

    OpenAIRE

    Su, Leon L.; Iwai, Hideyuki; Lin, Jack T; Fathman, C. Garrison

    2009-01-01

    Ubiquitination of eukaryotic proteins regulates a broad range of cellular processes, including T cell activation and tolerance. We have previously demonstrated that GRAIL (gene related to anergy in lymphocytes), a transmembrane RING finger ubiquitin E3 ligase, initially described as induced during the induction of CD4 T cell anergy, is also expressed in resting CD4 T cells. In this study, we show that GRAIL can down-modulate the expression of CD83 (previously described as a cell surface marke...

  17. Carrier-Mediated Uptake of 1-(Malonylamino)cyclopropane-1-Carboxylic Acid in Vacuoles Isolated from Catharanthus roseus Cells 1

    Science.gov (United States)

    Bouzayen, Mondher; Latché, Alain; Pech, Jean-Claude; Marigo, Gérard

    1989-01-01

    The uptake of 1-(malonylamino)cyclopropane-1-carboxylic acid (MACC), the conjugated form of the ethylene precursor, into vacuoles isolated from Catharanthus roseus cells has been studied by silicone layer floatation filtering. The transport across the tonoplast of MACC is stimulated fourfold by 5 millimolar MgATP, has a Km of about 2 millimolar, an optimum pH around 7, and an optimum temperature at 30°C. Several effectors known to inhibit ATPase (N,N′-dicyclohexylcarbodiimide) and to collapse the transtonoplastic H+ electrochemical gradient (carbonylcyanide m-chlorophenylhydrazone, gramicidin, and benzylamine) all reduced MACC uptake. Abolishing the membrane potential with SCN− and valinomycin also greatly inhibited MACC transport. Our data demonstrate that MACC accumulates in the vacuole against a concentration gradient by means of a proton motive force generated by a tonoplastic ATPase. The involvement of a protein carrier is suggested by the strong inhibition of uptake by compounds known to block SH—, OH—, and NH2— groups. MACC uptake is antagonized competitively by malonyl-d-tryptophan, indicating that the carrier also accepts malonyl-d-amino acids. Neither the moities of these compounds taken separately [1-aminocyclopropane-1-carboxylic acid, malonate, d-tryptophan or d-phenylalanine] nor malate act as inhibitors of MACC transport. The absence of inhibition of malate uptake by MACC suggests that MACC and malate are taken up by two different carriers. We propose that the carrier identified here plays an important physiological role in withdrawing from the cytosol MACC and malonyl-d-amino acids generated under stress conditions. PMID:16667182

  18. Identification and Characterization of an 18-Kilodalton, VAMP-Like Protein in Suspension-Cultured Carrot Cells1

    Science.gov (United States)

    Gasparian, Marine; Pusterla, Michele; Baldan, Barbara; Downey, Patrick M.; Rossetto, Ornella; de Laureto, Patrizia Polverino; Filippini, Francesco; Terzi, Mario; Schiavo, Fiorella Lo

    2000-01-01

    Polyclonal antibodies raised against rat vesicle associated membrane protein-2 (VAMP-2) recognized, in carrot (Daucus carota) microsomes, two major polypeptides of 18 and 30 kD, respectively. A biochemical separation of intracellular membranes by a sucrose density gradient co-localized the two polypeptides as resident in light, dense microsomes, corresponding to the endoplasmic reticulum-enriched fractions. Purification of coated vesicles allowed us to distinguish the subcellular location of the 18-kD polypeptide from that of 30 kD. The 18-kD polypeptide is present in the non-clathrin-coated vesicle peak. Like other VAMPs, the carrot 18-kD polypeptide is proteolyzed by tetanus toxin after separation of coatomers. Amino acid sequence analysis of peptides obtained by digestion of the 18-kD carrot polypeptide with the endoproteinase Asp-N confirms it to be a member of the VAMP family, as is suggested by its molecular weight, vesicular localization, and toxin-induced cleavage. PMID:10631246

  19. Association of the frequency of peripheral natural killer T cells with nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Cheng-Fu Xu; Chao-Hui Yu; You-Ming Li; Lei Xu; Juan Du; Zhe Shen

    2007-01-01

    AIM: To investigate whether changes in the frequency of peripheral natural killer T (NKT) cells were correlated with liver disease in patients who had metabolic predispositions to nonalcoholic fatty liver disease (NAFLD).METHODS: Peripheral blood samples were obtained from 60 Chinese NAFLD patients and 60 age and gender matched healthy controls. The frequency of peripheral NKT cells was detected by flow cytometry. Clinical and laboratory data were collected for further analysis.RESULTS: NAFLD patients had a lower frequency of peripheral NKT cells than healthy controls (1.21% ± 0.06% vs 1.62% ± 0.07%, P < 0.001). Further analysis revealed that the frequency of peripheral NKT cells was negatively correlated with body mass index, waist circumference and serum levels of alanine aminotransferase. Logistic regression analysis revealed that elevated body mass index [hazard ratio (HR):2.991], aspartate aminotransferase levels (HR: 1.148)and fasting blood sugar (HR: 3.133) increased the risk of NAFLD, whereas an elevated frequency of peripheral NKT cells (HR: 0.107) decreased the risk.CONCLUSION: Changes in the frequency of peripheral NKT cells were correlated with NAFLD and a decreased frequency of peripheral NKT cells was a risk factor for NAFLD.

  20. Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection.

    Science.gov (United States)

    Kamaladasa, A; Wickramasinghe, N; Adikari, T N; Gomes, L; Shyamali, N L A; Salio, M; Cerundolo, V; Ogg, G S; Malavige, G Neelika

    2016-08-01

    Invariant natural killer T (iNKT) cells are capable of rapid activation and production of cytokines upon recognition of antigenic lipids presented by CD1d molecules. They have been shown to play a significant role in many viral infections and were observed to be highly activated in patients with acute dengue infection. In order to characterize further their role in dengue infection, we investigated the proportion of iNKT cells and their phenotype in adult patients with acute dengue infection. The functionality of iNKT cells in patients was investigated by both interferon (IFN)-γ and interleukin (IL)-4 ex-vivo enzyme-linked immunospot (ELISPOT) assays following stimulation with alpha-galactosyl-ceramide (αGalCer). We found that circulating iNKT cell proportions were significantly higher (P = 0·03) in patients with acute dengue when compared to healthy individuals and were predominantly of the CD4(+) subset. iNKT cells of patients with acute dengue had reduced proportions expressing CD8α and CD161 when compared to healthy individuals. The iNKT cells of patients were highly activated and iNKT activation correlated significantly with dengue virus-specific immunoglobulin (Ig)G antibody levels. iNKT cells expressing Bcl-6 (P = 0·0003) and both Bcl-6 and inducible T cell co-stimulator (ICOS) (P = 0·006) were increased significantly in patients when compared to healthy individuals. Therefore, our data suggest that in acute dengue infection there is an expansion of highly activated CD4(+) iNKT cells, with reduced expression of CD161 markers. PMID:26874822

  1. Invariant Natural Killer T cells are not affected by lysosomal storage in patients with Niemann-Pick disease type C

    OpenAIRE

    Speak, Anneliese O; Platt, Nicholas; Salio, Mariolina; te Vruchte, Danielle Taylor; Smith, David A.; Shepherd, Dawn; Veerapen, Natacha; Besra, Gurdyal; Yanjanin, Nicole M.; Simmons, Louise; Imrie, Jackie; Wraith, James E.; Lachmann, Robin; Hartung, Ralf; Runz, Heiko

    2012-01-01

    Invariant Natural Killer T (iNKT) cells are a specialised subset of T cells that are restricted to the MHC class I like molecule, CD1d. The ligands for iNKT cells are lipids, with the canonical superagonist being α-galactosylceramide, a non-mammalian glycosphingolipid. Trafficking of CD1d through the lysosome is required for the development of murine iNKT cells. Niemann-Pick type C (NPC) disease is a lysosomal storage disorder caused by dysfunction in either of two lysosomal proteins, NPC1 or...

  2. Prognostic Factors and Long-term Treatment Outcome in 64 Cases of Early Stage Nasal NK/T- cell Lymphoma%64例早期鼻腔NK/T细胞淋巴瘤的疗效和预后分析

    Institute of Scientific and Technical Information of China (English)

    马辉辉; 高劲; 张红雁; 马军; 赵于飞; 吴韦炜; 刘云琴; 钱立庭

    2007-01-01

    目的:回顾性分析64例早期原发鼻腔NK/T细胞淋巴瘤患者的疗效,探讨其预后因素.方法:收集1993年6月至2005年10月间收治的64例早期原发鼻腔NK/T细胞淋巴瘤患者的资料.根据Ann Arbor分期标准,64例患者均为Ⅰ E/Ⅱ E期,单纯放疗23例,其余41例接受放、化联合治疗.单因素分析采用Kaplan-Meier法,多因素分析运用Cox比例风险模型.结果:全组中位生存时间41个月,5年总生存(OS)率为59.17%.单纯放疗组和联合放化疗组5年OS率分别是57.86%和61.45%(P=0.47),二者对生存率影响无明显统计学差异.多因素回归分析表明,治疗前PS评分≥2分、初诊时病灶超腔、首程治疗完全缓解率(CR)低是预后不良的独立因素.结论:对早期鼻腔NK/T细胞淋巴瘤的治疗,放疗加CHOP方案化疗对远期生存率没有提高.治疗前PS评分、初诊时病灶是否超腔、首程治疗完全缓解率,可作为判断鼻腔NK/T细胞淋巴瘤临床预后的参考指标.

  3. Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation

    OpenAIRE

    Kawasaki, Norihito; Vela, Jose Luis; Nycholat, Corwin M.; Rademacher, Christoph; Khurana, Archana; van Rooijen, Nico; Crocker, Paul R.; Kronenberg, Mitchell; Paulson, James C.

    2013-01-01

    Invariant natural killer T (iNKT) cells induce a protective immune response triggered by foreign glycolipid antigens bound to CD1d on antigen-presenting cells (APCs). A limitation of using glycolipid antigens to stimulate immune responses in human patients has been the inability to target them to the most effective APCs. Recent studies have implicated phagocytic CD169+ macrophages as major APCs in lymph nodes for priming iNKT cells in mice immunized with glycolipid antigen in particulate form...

  4. Assessment of Shear Strength in Silty Soils

    Directory of Open Access Journals (Sweden)

    Stefaniak Katarzyna

    2015-06-01

    Full Text Available The article presents a comparison of shear strength values in silty soils from the area of Poznań, determined based on selected Nkt values recommended in literature, with values of shear strength established on the basis of Nkt values recommended by the author. Analysed silty soils are characterized by the carbonate cementation zone, which made it possible to compare selected empirical coefficients both in normally consolidated and overconsolidated soils

  5. Mechanisms of Innate Lymphoid Cell and Natural Killer T Cell Activation during Mucosal Inflammation

    OpenAIRE

    David Nau; Nora Altmayer; Jochen Mattner

    2014-01-01

    Mucosal surfaces in the airways and the gastrointestinal tract are critical for the interactions of the host with its environment. Due to their abundance at mucosal tissue sites and their powerful immunomodulatory capacities, the role of innate lymphoid cells (ILCs) and natural killer T (NKT) cells in the maintenance of mucosal tolerance has recently moved into the focus of attention. While NKT cells as well as ILCs utilize distinct transcription factors for their development and lineage dive...

  6. Extra Nodal NK/T-Cell Lymphoma Nasal Type: Efficacy of Pegaspargase Report of Two Patients from the United Sates and Review of Literature

    OpenAIRE

    Reyes, Vincent Edgar; Al-Saleem, Tahseen; Robu, Valentin G.; Smith, Mitchell R.

    2009-01-01

    Extranodal NK/T cell lymphoma nasal type is an EBV driven non-Hodgkin lymphoma, rare in the United States, with no known satisfactory treatment. Two patients with this entity refractory to CHOP chemotherapy responded to single agent pegaspargase (pegylated L-asparaginase). A 64-year-old Caucasian woman presented with extranodal NK/T lymphoma nasal type on her left buttocks. After initial treatment with loco-regional irradiation and CHOP, she developed extensive lower extremity lesions, and su...

  7. Symposium 3: Vitamin D and immune function: from pregnancy to adolescence: Vitamin D, invariant natural killer T-cells and experimental autoimmune disease

    OpenAIRE

    Cantorna, Margherita T.; Zhao, Jun; Yang, Linlin

    2012-01-01

    Vitamin D is an important regulator of the immune system in general and multiple sclerosis in particular. Experimentally (i), invariant natural killer T (iNKT) cells have been shown to be important suppressors of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE; an animal model of multiple sclerosis). Conversely, in experimental allergic asthma iNKT cells are required for disease induction and are therefore pathogenic. The active form of vitamin D (calcitriol) suppre...

  8. Lysophospholipid presentation by CD1d and recognition by a human Natural Killer T-cell receptor

    Energy Technology Data Exchange (ETDEWEB)

    López-Sagaseta, Jacinto; Sibener, Leah V.; Kung, Jennifer E.; Gumperz, Jenny; Adams, Erin J. (UC); (UW-MED)

    2014-10-02

    Invariant Natural Killer T (iNKT) cells use highly restricted {alpha}{beta} T cell receptors (TCRs) to probe the repertoire of lipids presented by CD1d molecules. Here, we describe our studies of lysophosphatidylcholine (LPC) presentation by human CD1d and its recognition by a native, LPC-specific iNKT TCR. Human CD1d presenting LPC adopts an altered conformation from that of CD1d presenting glycolipid antigens, with a shifted {alpha}1 helix resulting in an open A pocket. Binding of the iNKT TCR requires a 7-{angstrom} displacement of the LPC headgroup but stabilizes the CD1d-LPC complex in a closed conformation. The iNKT TCR CDR loop footprint on CD1d-LPC is anchored by the conserved positioning of the CDR3{alpha} loop, whereas the remaining CDR loops are shifted, due in part to amino-acid differences in the CDR3{beta} and J{beta} segment used by this iNKT TCR. These findings provide insight into how lysophospholipids are presented by human CD1d molecules and how this complex is recognized by some, but not all, human iNKT cells.

  9. Contribution of Invariant Natural Killer T Cells to Skin Wound Healing.

    Science.gov (United States)

    Tanno, Hiromasa; Kawakami, Kazuyoshi; Ritsu, Masae; Kanno, Emi; Suzuki, Aiko; Kamimatsuno, Rina; Takagi, Naoyuki; Miyasaka, Tomomitsu; Ishii, Keiko; Imai, Yoshimichi; Maruyama, Ryoko; Tachi, Masahiro

    2015-12-01

    In the present study, we determined the contribution of invariant natural killer T (iNKT) cells to the skin wound healing process. In iNKT cell-deficient (Jα18KO) mice lacking iNKT cells, wound closure was significantly delayed compared with wild-type mice. Collagen deposition, expression of α-smooth muscle actin and CD31, and wound breaking strength were significantly attenuated in Jα18KO mice. The adoptive transfer of liver mononuclear cells from wild-type but not from Jα18KO or interferon (IFN)-γ gene-disrupted (IFN-γKO) mice resulted in the reversal of this impaired wound healing in Jα18KO mice. IFN-γ expression was induced in the wounded tissues, which was significantly decreased at 6, 12, and 24 hours, but increased on day 3 after wounding in Jα18KO mice. The main source of the late-phase IFN-γ production in Jα18KO mice were neutrophils rather than NK cells and T cells. Administration of α-galactosylceramide, an activator of iNKT cells, resulted in the acceleration of wound healing on day 3 in wild-type mice. This effect was not observed in IFN-γKO mice. These results indicate that iNKT cells play important roles in wound healing. The iNKT cell-induced IFN-γ production may regulate the wound healing process in the early phase.

  10. Characterization of the natural killer T-cell response in an adoptive transfer model of atherosclerosis.

    Science.gov (United States)

    VanderLaan, Paul A; Reardon, Catherine A; Sagiv, Yuval; Blachowicz, Lydia; Lukens, John; Nissenbaum, Michael; Wang, Chyung-Ru; Getz, Godfrey S

    2007-03-01

    Natural killer T (NKT) cells have recently been implicated in atherogenesis, primarily for their ability to recognize and respond to lipid antigens. Because the atherosclerotic lesion is characterized by the retention and modification of lipids in the vascular wall, NKT cells may be involved in promoting the local vascular inflammatory response. Here, we investigate the proatherogenic role of NKT cells in an adoptive transfer model of atherosclerosis, using as recipients immune-deficient, atherosclerosis-susceptible RAG1(-/-)LDLR(-/-) mice. The adoptive transfer of an NKT cell-enriched splenocyte population from Valpha14Jalpha18 T-cell receptor transgenic mice resulted in a 73% increase in aortic root lesion area compared with recipients of NKT cell-deficient splenocytes derived from CD1d(-/-) mice after 12 weeks of Western-type diet feeding. The total serum from hypercholesterolemic mice leads to a small but significant activation of Valpha14Jalpha18 T-cell receptor-expressing hybridoma line by dendritic cells that is CD1d-dependent. Therefore, these studies demonstrate that NKT cells are proatherogenic in the absence of exogenous stimulation, and this activity is likely associated with endogenous lipid antigens carried by lipoproteins in the circulation and perhaps also in the atherosclerotic plaque.

  11. Regulation of development and function of different T cell subtypes by Rel/NF-{kappa}B family members

    Energy Technology Data Exchange (ETDEWEB)

    Vallabhapurapu, S.

    2004-09-01

    This study reveals the requirement of distinct members of the Rel/NF-{kappa}B family in both hematopoietic and non-hematopoietic cells for the development of thymic NKT cells. Activation of NF-{kappa}B via the classical I{kappa}B{alpha}-regulated pathway is required within the NKT precursors for their efficient maturation from NK1.1{sup -} precursors to mature NK1.1{sup +} NKT cells. The Rel/NF-{kappa}B family member RelB, on the other hand, is required in thymic stromal cells for the generation of very early NK1.1{sup -} precursors. NF-{kappa}B-inducing kinase (NIK) has also been shown to be required in thymic stromal cells for NKT cell development and this study demonstrates that NIK specifically regulates both constitutive and signal-induced DNA binding of RelB, but not RelA. Moreover, NIK-induced DNA binding of RelB depends on the processing of inhibitory p100 to p52, revealing an alternate pathway of NF-{kappa}B induction. Thus, Rel/NF-{kappa}B complexes activated by the classical I{kappa}B{alpha}-regulated pathway in NKT precursors and an alternate NIK/p100/RelB pathway in thymic stromal cells regulate different stages of NKT cell development. (orig.)

  12. Id2 regulates hyporesponsive invariant natural killer T cells

    Science.gov (United States)

    Stradner, Martin H; Cheung, Kitty P; Lasorella, Anna; Goldrath, Ananda W; D’Cruz, Louise M

    2016-01-01

    While the invariant natural killer T (iNKT)-cell response to primary stimulation with the glycolipid, α-galactosylceramide (αGalCer), is robust, the secondary response to this stimulus is muted resulting in a hyporesponsive state characterized by anti-inflammatory interleukin-10 (IL-10) production and high expression of programmed cell death 1 (PD1) and neuropilin 1 (NRP1). The E protein transcription factors and their negative regulators, the Id proteins, have previously been shown to regulate iNKT cell thymic development, subset differentiation and peripheral survival. Here, we provide evidence that the expression of the transcriptional regulator Id2 is downregulated upon stimulation of iNKT cells with their cognate antigen. Moreover, loss of Id2 expression by iNKT cells resulted in a hyporesponsive state, with splenic Id2-deficient iNKT cells expressing low levels of TBET, high levels of PD1 and NRP1 and production of IL-10 upon stimulation. We propose that downregulation of Id2 expression is an essential component of induction of the anti-inflammatory, hyporesponsive state in iNKT cells. PMID:26880074

  13. Specific deletion of LDL receptor-related protein on macrophages has skewed in vivo effects on cytokine production by invariant natural killer T cells.

    Directory of Open Access Journals (Sweden)

    Roman Covarrubias

    Full Text Available Expression of molecules involved in lipid homeostasis such as the low density lipoprotein receptor (LDLr on antigen presenting cells (APCs has been shown to enhance invariant natural killer T (iNKT cell function. However, the contribution to iNKT cell activation by other lipoprotein receptors with shared structural and ligand binding properties to the LDLr has not been described. In this study, we investigated whether a structurally related receptor to the LDLr, known as LDL receptor-related protein (LRP, plays a role in iNKT cell activation. We found that, unlike the LDLr which is highly expressed on all immune cells, the LRP was preferentially expressed at high levels on F4/80+ macrophages (MΦ. We also show that CD169+ MΦs, known to present antigen to iNKT cells, exhibited increased expression of LRP compared to CD169- MΦs. To test the contribution of MΦ LRP to iNKT cell activation we used a mouse model of MΦ LRP conditional knockout (LRP-cKO. LRP-cKO MΦs pulsed with glycolipid alpha-galactosylceramide (αGC elicited normal IL-2 secretion by iNKT hybridoma and in vivo challenge of LRP-cKO mice led to normal IFN-γ, but blunted IL-4 response in both serum and intracellular expression by iNKT cells. Flow cytometric analyses show similar levels of MHC class-I like molecule CD1d on LRP-cKO MΦs and normal glycolipid uptake. Survey of the iNKT cell compartment in LRP-cKO mice revealed intact numbers and percentages and no homeostatic disruption as evidenced by the absence of programmed death-1 and Ly-49 surface receptors. Mixed bone marrow chimeras showed that the inability iNKT cells to make IL-4 is cell extrinsic and can be rescued in the presence of wild type APCs. Collectively, these data demonstrate that, although MΦ LRP may not be necessary for IFN-γ responses, it can contribute to iNKT cell activation by enhancing early IL-4 secretion.

  14. Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model.

    Science.gov (United States)

    Nambiar, Jonathan; Clarke, Adam W; Shim, Doris; Mabon, David; Tian, Chen; Windloch, Karolina; Buhmann, Chris; Corazon, Beau; Lindgren, Matilda; Pollard, Matthew; Domagala, Teresa; Poulton, Lynn; Doyle, Anthony G

    2015-01-01

    CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1β, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical.

  15. Potent neutralizing anti-CD1d antibody reduces lung cytokine release in primate asthma model

    Science.gov (United States)

    Nambiar, Jonathan; Clarke, Adam W; Shim, Doris; Mabon, David; Tian, Chen; Windloch, Karolina; Buhmann, Chris; Corazon, Beau; Lindgren, Matilda; Pollard, Matthew; Domagala, Teresa; Poulton, Lynn; Doyle, Anthony G

    2015-01-01

    CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1β, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical. PMID:25751125

  16. Cytosine deaminase adenoviral vector and 5-fluorocytosine selectively reduce breast cancer cells 1 million-fold when they contaminate hematopoietic cells: a potential purging method for autologous transplantation.

    Science.gov (United States)

    Garcia-Sanchez, F; Pizzorno, G; Fu, S Q; Nanakorn, T; Krause, D S; Liang, J; Adams, E; Leffert, J J; Yin, L H; Cooperberg, M R; Hanania, E; Wang, W L; Won, J H; Peng, X Y; Cote, R; Brown, R; Burtness, B; Giles, R; Crystal, R; Deisseroth, A B

    1998-07-15

    Ad.CMV-CD is a replication incompetent adenoviral vector carrying a cytomegalovirus (CMV)-driven transcription unit of the cytosine deaminase (CD) gene. The CD transcription unit in this vector catalyzes the deamination of the nontoxic pro-drug, 5-fluorocytosine (5-FC), thus converting it to the cytotoxic drug 5-fluorouracil (5-FU). This adenoviral vector prodrug activation system has been proposed for use in selectively sensitizing breast cancer cells, which may contaminate collections of autologous stem cells products from breast cancer patients, to the toxic effects of 5-FC, without damaging the reconstitutive capability of the normal hematopoietic cells. This system could conceivably kill even the nondividing breast cancer cells, because the levels of 5-FU generated by this system are 10 to 30 times that associated with systemic administration of 5-FU. The incorporation of 5-FU into mRNA at these high levels is sufficient to disrupt mRNA processing and protein synthesis so that even nondividing cells die of protein starvation. To test if the CD adenoviral vector sensitizes breast cancer cells to 5-FC, we exposed primary explants of normal human mammary epithelial cells (HMECs) and the established breast cancer cell (BCC) lines MCF-7 and MDA-MB-453 to the Ad.CMV-CD for 90 minutes. This produced a 100-fold sensitization of these epithelial cells to the effects of 48 hours of exposure to 5-FC. We next tested the selectivity of this system for BCC. When peripheral blood mononuclear cells (PBMCs), collected from cancer patients during the recovery phase from conventional dose chemotherapy-induced myelosuppression, were exposed to the Ad.CMV-CD for 90 minutes in serum-free conditions, little or no detectable conversion of 5-FC into 5-FU was seen even after 48 hours of exposure to high doses of 5-FC. In contrast, 70% of 5-FC was converted into the cytotoxic agent 5-FU when MCF-7 breast cancer cells (BCCs) were exposed to the same Ad.CMV-CD vector followed by 5-FC for 48 hours. All of the BCC lines tested were shown to be sensitive to infection by adenoviral vectors when exposed to a recombinant adenoviral vector containing the reporter gene betagalactosidase (Ad.CMV-betagal). In contrast, less than 1% of the CD34-selected cells and their more immature subsets, such as the CD34+CD38- or CD34(+)CD33- subpopulations, were positive for infection by the Ad.CMV-betagal vector, as judged by fluorescence-activated cell sorting (FACS) analysis, when exposed to the adenoviral vector under conditions that did not commit the early hematopoietic precursor cells to maturation. When artificial mixtures of hematopoietic cells and BCCs were exposed for 90 minutes to the Ad.CMV-CD vector and to 5-FC for 10 days or more, a greater than 1 million fold reduction in the number of BCCs, as measured by colony-limiting dilution assays, was observed. To test if the conditions were damaging for the hematopoietic reconstituting cells, marrow cells collected from 5-FU-treated male donor mice were incubated with the cytosine deaminase adenoviral vector and then exposed to 5-FC either for 4 days in vitro before transplantation or for 14 days immediately after transplantation in vivo. There was no significant decrease in the reconstituting capability of the male marrow cells, as measured by their persistence in female irradiated recipients for up to 6 months after transplantation. These observations suggest that adenovirus-mediated gene transfer of the Escherichia coli cytosine deaminase gene followed by exposure to the nontoxic pro-drug 5-FC may be a potential strategy to selectively reduce the level of contaminating BCCs in collections of hematopoietic cells used for autografts in breast cancer patients.

  17. Calculation Package for the Analysis of Performance of Cells 1-6, with Underdrain, of the Environmental Management Waste Management Facility Oak Ridge, Tennessee

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales D.

    2010-03-30

    This calculation package presents the results of an assessment of the performance of the 6 cell design of the Environmental Management Waste Management Facility (EMWMF). The calculations show that the new cell 6 design at the EMWMF meets the current WAC requirement. QA/QC steps were taken to verify the input/output data for the risk model and data transfer from modeling output files to tables and calculation.

  18. Alteration of AMPA Receptor-Mediated Synaptic Transmission by Alexa Fluor 488 and 594 in Cerebellar Stellate Cells1 2 3

    OpenAIRE

    Maroteaux, Matthieu; Liu, Siqiong June

    2016-01-01

    Abstract The fluorescent dyes, Alexa Fluor 488 and 594 are commonly used to visualize dendritic structures and the localization of synapses, both of which are critical for the spatial and temporal integration of synaptic inputs. However, the effect of the dyes on synaptic transmission is not known. Here we investigated whether Alexa Fluor dyes alter the properties of synaptic currents mediated by two subtypes of AMPA receptors (AMPARs) at cerebellar stellate cell synapses. In naive mice, GluA...

  19. Suppression of Murine Allergic Airway Disease by IL-2:Anti-IL-2 Monoclonal Antibody-Induced Regulatory T Cells1

    OpenAIRE

    Wilson, Mark S; Pesce, John T; Thirumalai R Ramalingam; Thompson, Robert W.; Cheever, Allen; Wynn, Thomas A

    2008-01-01

    Regulatory T cells (Treg) play a decisive role in many diseases including asthma and allergen-induced lung inflammation. However, little progress has been made developing new therapeutic strategies for pulmonary disorders. In the current study we demonstrate that cytokine:antibody complexes of IL-2 and anti-IL-2 mAb reduce the severity of allergen-induced inflammation in the lung by expanding Tregs in vivo. Unlike rIL-2 or anti-IL-2 mAb treatment alone, IL-2:anti-IL-2 complexes dampened airwa...

  20. Isolation of Genes that Are Preferentially Expressed at the G1/S Boundary during the Cell Cycle in Synchronized Cultures of Catharanthus roseus Cells 1

    Science.gov (United States)

    Kodama, Hiroaki; Ito, Masaki; Hattori, Tsukaho; Nakamura, Kenzo; Komamine, Atsushi

    1991-01-01

    A cDNA library was screened for genes that may be involved in the progression of the cell cycle of cells of higher plants. The Catharanthus roseus L. (G) Don. cells were synchronized by the double phosphate starvation method, and a λgt11 cDNA library was prepared using poly(A)+ RNA from cells in the S phase of the cell cycle. Two independent sequences, cyc02 and cyc07, were identified by differential screening. The levels of cyc02 and cyc07 mRNAs increased dramatically, but transiently, at the G1/S boundary of the cell cycle. High levels of cyc02 mRNA, but not of cyc07 mRNA, were also present in cells arrested at the G1 phase by phosphate starvation. In an asynchronous batch culture, cyc02 and cyc07 mRNAs accumulated transiently at different stages of the growth cycle, cyc02 mRNA early in the stationary phase, and cyc07 mRNA in the midlogarithmic phase. When the proliferation of cells was arrested by nutrient starvation, i.e. by sucrose or nitrogen starvation, the relative amounts of the cyc02 and cyc07 mRNAs decreased. These results indicate that cyc02 and cyc07 contain nucleotide sequences from growth-related genes. The analysis of nucleotide sequence of cyc02 shows that the predicted product of this gene is basic and is composed of 101 amino acids. No significant homology to other known proteins was detected. Images Figure 1 Figure 4 Figure 5 PMID:16667998

  1. Phase-Specific Polypeptides and Poly(A)+ RNAs during the Cell Cycle in Synchronous Cultures of Catharanthus roseus Cells 1

    Science.gov (United States)

    Kodama, Hiroaki; Kawakami, Naoto; Watanabe, Akira; Komamine, Atsushi

    1989-01-01

    This study shows an overall analysis of gene expression during the cell cycle in synchronous suspension cultures of Catharanthus roseus cells. First, the cellular cytoplasmic proteins were fractionated by two-dimensional gel electrophoresis and visualized by staining with silver. Seventeen polypeptides showed qualitative or quantitative changes during the cell cycle. Second, the rates of synthesis of cytoplasmic proteins were also investigated by autoradiography by labeling cells with [35S]methionine at each phase of the cell cycle. The rates of synthesis of 13 polypeptides were found to vary during the cell cycle. The silverstained electrophoretic pattern of proteins in the G2 phase in particular showed characteristic changes in levels of polypeptides, while the rates of synthesis of polypeptides synthesized during the G2 phase did not show such phase-specific changes. This result suggests that posttranslational processing of polypeptides occurs during or prior to the G2 phase. In the G1 and S phases and during cytokinesis, several other polypeptides were specifically synthesized. Finally, the variation of mRNAs was analyzed from the autoradiograms of in vitro translation products of poly(A)+ RNA isolated at each phase. Three poly(A)+ RNAs increased in amount from the G1 to the S phase and one poly (A)+ RNA increased preferentially from the G2 phase to cytokinesis. Images Figure 1 Figure 3 Figure 4 Figure 6 Figure 7 Figure 8 Figure 10 Figure 11 Figure 12 PMID:16666641

  2. Recognition of microbial glycolipids by Natural Killer T cells

    Directory of Open Access Journals (Sweden)

    Dirk Michael Zajonc

    2015-08-01

    Full Text Available T cells can recognize microbial antigens when presented by dedicated antigen-presenting molecules. While peptides are presented by classical members of the Major Histocompatibility (MHC family (MHC I and II, lipids, glycolipids and lipopeptides can be presented by the non-classical MHC member CD1. The best studied subset of lipid-reactive T cells are Type I Natural killer T (iNKT cells that recognize a variety of different antigens when presented by the non-classical MHCI homolog CD1d. iNKT cells have been shown to be important for the protection against various microbial pathogens, including B. burgdorferi the causative agents of Lyme disease and S. pneumoniae, which causes pneumococcal meningitis and community-acquired pneumonia. Both pathogens carry microbial glycolipids that can trigger the T cell antigen receptor (TCR, leading to iNKT cell activation. iNKT cells have an evolutionary conserved TCR alpha chain, yet retain the ability to recognize structurally diverse glycolipids. They do so using a conserved recognition mode, in which the TCR enforces a conserved binding orientation on CD1d. TCR binding is accompanied by structural changes within the TCR binding site of CD1d, as well as the glycolipid antigen itself. In addition to direct recognition of microbial antigens, iNKT cells can also be activated by a combination of cytokines (IL-12/IL-18 and TCR stimulation. Many microbes carry TLR antigens and microbial infections can lead to TLR activation. The subsequent cytokine response in turn lower the threshold of TCR mediated iNKT cell activation, especially when weak microbial or even self-antigens are presented during the cause of the infection. In summary, iNKT cells can be directly activated through TCR triggering of strong antigens, while cytokines produced by the innate immune response may be necessary for TCR triggering and iNKT cell activation in the presence of weak antigens. Here we will review the molecular basis of iNKT cell

  3. Inhibition effect of natural killer T cells on transplantation hepatocellular carcinoma in mice%自然杀伤T细胞对小鼠肝癌移植瘤的抑制作用

    Institute of Scientific and Technical Information of China (English)

    Fuxing Chen; Hongdan Zhao; Nanzheng Zhang; Junquan Liu; Zhonghai Zhou; Leiqing Sun; Yu Zhou

    2011-01-01

    Objective:The aim of this study was to investigate the inhibition effect of natural killer T (NKT) cells on transplantation hepatocellular carcinoma in mice. Methods:α-galactosylceramide (α-GalCer)-pulsed DC and HepS were prepared as stimulus. Hepatoma xenograft model was established and mice were randomly divided into 4 groups (n = 13 each group):(1)control group, intravenous injection of the same volume of saline. (2) mature DC group, intravenous injection of mature DC cells (4 × 106 cells). (3) α-GalCer-pulsed HepS group, intravenous injection of α-GalCer-pulsed HepS (4 × 106 cells). (4) α-GalCer -pulsed mature DC group, intravenous injection of α-GalCer-pulsed DC (4 × 106 cells). The changes of tumor volume in mice and survival period were measured every 2 days. Percentage of NKT cells in spleens and cytotoxicity of spleen cells were detected by flow cytometry. Tumor tissues were analyzed by histopathological examination. Results:In α-GalCerpulsed Heps and DC groups, the average survival period was prolonged and tumor volume was markedly decreased, spleen cells and NKT cells were significantly increased, and tumor necrosis was evident, compared to the control group. Conclusion:α-GalCer-pulsed DC and HepS could activate NKT cells in vivo, also increase NKT cells cytotoxicity, inhibit the growth of hepatomas and prolong survival period.

  4. Interferon-γ Expression in Natural Killer Cells and Natural Killer T Cells Is Suppressed in Early Pregnancy

    Institute of Scientific and Technical Information of China (English)

    Yongyun Shi; Bin Ling; Ying Zhou; Ting Gao; Dingqing Feng; Min Xiao; Lin Feng

    2007-01-01

    Recent study has suggested that innate immune system might play an important role in pregnancy progression. In this study, to investigate whether NK cells and NKT cells, instead of T cells, are the dominant populations of peripheral blood in early pregnancy, flow cytometry was used to detect the percentage and intracellular cytokine expressions of T cells, NK cells, NKT cells in peripheral blood of non-pregnant women and early pregnant women.In our result, the percentages of NK cells and NKT cells were significantly increased in pregnancy compared to non-pregnancy. However, the percentage of T cells was not changed. We did not detect the Th2-dominance of total lymphocytes or T cells in peripheral blood of early pregnant women and there were also no significant changes of type 1 and type 2 cytokines in T cells, but IFN-γ production in both NK and NKT cells was decreased in early pregnancy. These results suggest that the innate immune system including NK cells and NKT cells should play a pivotal role in pregnancy progression. Type 1/type 2 shift mechanisms in innate immune system during the human early pregnancy should be paid more attention.

  5. Altered effector function of peripheral cytotoxic cells in COPD

    Directory of Open Access Journals (Sweden)

    Corne Jonathan M

    2009-06-01

    Full Text Available Abstract Background There is mounting evidence that perforin and granzymes are important mediators in the lung destruction seen in COPD. We investigated the characteristics of the three main perforin and granzyme containing peripheral cells, namely CD8+ T lymphocytes, natural killer (NK; CD56+CD3- cells and NKT-like (CD56+CD3+ cells. Methods Peripheral blood mononuclear cells (PBMCs were isolated and cell numbers and intracellular granzyme B and perforin were analysed by flow cytometry. Immunomagnetically selected CD8+ T lymphocytes, NK (CD56+CD3- and NKT-like (CD56+CD3+ cells were used in an LDH release assay to determine cytotoxicity and cytotoxic mechanisms were investigated by blocking perforin and granzyme B with relevant antibodies. Results The proportion of peripheral blood NKT-like (CD56+CD3+ cells in smokers with COPD (COPD subjects was significantly lower (0.6% than in healthy smokers (smokers (2.8%, p +CD3- cells from COPD subjects were significantly less cytotoxic than in smokers (16.8% vs 51.9% specific lysis, p +CD3+ cells (16.7% vs 52.4% specific lysis, p +CD3- and NKT-like (CD56+CD3+ cells from smokers and HNS. Conclusion In this study, we show that the relative numbers of peripheral blood NK (CD56+CD3- and NKT-like (CD56+CD3+ cells in COPD subjects are reduced and that their cytotoxic effector function is defective.

  6. Stimulation of Natural Killer T Cells by Glycolipids

    Directory of Open Access Journals (Sweden)

    Brian L. Anderson

    2013-12-01

    Full Text Available Natural killer T (NKT cells are a subset of T cells that recognize glycolipid antigens presented by the CD1d protein. The initial discovery of immunostimulatory glycolipids from a marine sponge and the T cells that respond to the compounds has led to extensive research by chemists and immunologists to understand how glycolipids are recognized, possible responses by NKT cells, and the structural features of glycolipids necessary for stimulatory activity. The presence of this cell type in humans and most mammals suggests that it plays critical roles in antigen recognition and the interface between innate and adaptive immunity. Both endogenous and exogenous natural antigens for NKT cells have been identified, and it is likely that glycolipid antigens remain to be discovered. Multiple series of structurally varied glycolipids have been synthesized and tested for stimulatory activity. The structural features of glycolipids necessary for NKT cell stimulation are moderately well understood, and designed compounds have proven to be much more potent antigens than their natural counterparts. Nevertheless, control over NKT cell responses by designed glycolipids has not been optimized, and further research will be required to fully reveal the therapeutic potential of this cell type.

  7. Intrahepatic natural killer T cell populations are increased in human hepatic steatosis

    Institute of Scientific and Technical Information of China (English)

    Michael Adler; Sarah Taylor; Kamalu Okebugwu; Herman Yee; Christine Fielding; George Fielding; Michael Poles

    2011-01-01

    AIM: To determine if natural killer T cell (NKT) populations are affected in nonalcoholic fatty liver disease(NAFLD).METHODS: Patients undergoing bariatric surgery underwent liver biopsy and blood sampling during surgery.The biopsy was assessed for steatosis and immunocyte infiltration. Intrahepatic lymphocytes (IHLs) were isolated from the remainder of the liver biopsy,and peripheral blood mononuclear cells (PBMCs) were isolated from the blood. Expression of surface proteins on both IHLs and PBMCs were quantified using flow cytometry.RESULTS: Twenty-seven subjects participated in this study. Subjects with moderate or severe steatosis had a higher percentage of intrahepatic CD3+/CD56+ NKT cells (38.6%) than did patients with mild steatosis(24.1%, P = 0.05) or those without steatosis (21.5%, P= 0.03). Patients with moderate to severe steatosis alsohad a higher percentage of NKT cells in the blood (12.3%) as compared to patients with mild steatosis (2.5% P =0.02) and those without steatosis (5.1%, P = 0.05).CONCLUSION: NKT cells are significantly increased in the liver and blood of patients with moderate to severe steatosis and support the role of NKT cells in NAFLD.

  8. Mice lacking natural killer T cells are more susceptible to metabolic alterations following high fat diet feeding.

    Directory of Open Access Journals (Sweden)

    Brittany V Martin-Murphy

    Full Text Available Current estimates suggest that over one-third of the adult population has metabolic syndrome and three-fourths of the obese population has non-alcoholic fatty liver disease (NAFLD. Inflammation in metabolic tissues has emerged as a universal feature of obesity and its co-morbidities, including NAFLD. Natural Killer T (NKT cells are a subset of innate immune cells that abundantly reside within the liver and are readily activated by lipid antigens. There is general consensus that NKT cells are pivotal regulators of inflammation; however, disagreement exists as to whether NKT cells exert pathogenic or suppressive functions in obesity. Here we demonstrate that CD1d(-/- mice, which lack NKT cells, were more susceptible to weight gain and fatty liver following high fat diet (HFD feeding. Compared with their WT counterparts, CD1d(-/- mice displayed increased adiposity and greater induction of inflammatory genes in the liver suggestive of the precursors of NAFLD. Calorimetry studies revealed a significant increase in food intake and trends toward decreased metabolic rate and activity in CD1d(-/- mice compared with WT mice. Based on these findings, our results suggest that NKT cells play a regulatory role that helps to prevent diet-induced obesity and metabolic dysfunction and may play an important role in mechanisms governing cross-talk between metabolism and the immune system to regulate energy balance and liver health.

  9. Clinical significance of peripheral blood CD4 + natural killer T cells in chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    JIANG Rong-long; LU Qiao-sheng; FENG Xiao-rong; LUO Kang-xian; HOU Jin-lin; FU Ning

    2001-01-01

    To understand the clinical significance of CD4+ natural killer T (NK-T) cells in chronic hepatitis B virus (HBV) infection. Methods: Peripheral blood mononuclear cells (PBMCs) from individuals with chronic HBV infection were separated routinely. After Induction with IL-12/IL-2 for 12 d, the proportion of CD4+NK-T cells in peripheral blood was determined by fluorescence activated cell sorter (FACS) analysis, and the cytotoxicity of peripheral blood lymphocytes (PBLs) was tested with a 4 h 51Cr release assay. Results: After IL-12/IL-2 induction, the proportion of CD4+ NK-T cells was (18.1±4.20)%, (6.95±2.85)% and (1.50±1.30)% in the healthy control, CAH and AsC respectively. That in the peripheral blood of chronic HBV infected individuals was lower than that in the healthy control. CD8+ NK-T cells was (2.70±1.10)%, (2.20±1.40)% and (3.10±0.70)%respectively. In vitro cytotoxicity assays against Wish cells revealed that the PBLs cytotoxicity reduced in chronic HBV infected individuals (P<0.05), and that in AsC group was significantly lower in comparison with CHB and healthy control groups. The cytotoxicity of CD4+ NK-T cells against Wish cells could be abolished by treating PBLs with either anti-CD4 Ab or anti-CD56 Ab and complement, and partially depleted by anti-CD8 Ab. Conclusion:The abnormal cellular immune function of chronic HBV infected individuals may be associated with the deficiency of CD4+ NK-T cells.

  10. Innate immune recognition and regulation in liver injury: A brief report from a series of studies

    Institute of Scientific and Technical Information of China (English)

    TIAN ZhiGang

    2009-01-01

    The discovery of innate immune receptors and the emergence of liver Immunology (high content of NK and NKT cells in liver) led to the second research summit in innate immunity since the finding of NK cells in the middle 1970s. Liver disease is one of the most dangerous threats to humans, and the pro-gress in innate immunology and liver immunology made it possible to re-explain the cellular end too-lecular immune mechanisms of liver disease. In the past ten years, we have found that innate recogni-tion of hepatic NK and NKT subsets were involved in murine liver injury. We established a novel NK cell-dependent acute murine hepatitis model by activating Toll-like receptor-3 (TLR-3) with an injection of poly I:C, which may mimic mild viral hepatitis (such as Chronic Hepatitis B). We observed that a network of innate immune cells including NK, NKT and Kupffer cells is involved in liver immune injury in our established NK cell-dependent murine model. We noted that TLR-3 on Kupffer ceils activated by pretreatment with poly I:C might protect against bacterial toxin (LPS)-induced fuIminant hepatitis by down-regulating TLR-4 function, while TLR-3 pre-activation of NK cells might reduce Con A-induced NKT cell-mediated fulminant hepatitis by blocking NKT cell recruitment to the liver. We also found that the oversensitivity to injury by immune stimulation in HBV (hepatitis B virus) transgenic mice (full HBV gene-tg or HBs-tg) correlated to the over-expression of Real, an NKG2D (natural killer cell group 2D) ligand of NK cells or CDld, a ligand of TCR-V14 of NKT cells, on HBV+ hepatocytes, which leads to an innate immune response against hepatocytes and is critical in liver immune injury and regeneration.

  11. Natural Killer Cells Determine Development of Allergen-induced Eosinophilic Airway Inflammation in Mice

    OpenAIRE

    Korsgren, Magnus; Persson, Carl G.A.; Sundler, Frank; Bjerke, Torbjörn; Hansson, Tony; Chambers, Benedict J.; Hong, Seokmann; Van Kaer, Luc; Ljunggren, Hans-Gustaf; Korsgren, Olle

    1999-01-01

    The earliest contact between antigen and the innate immune system is thought to direct the subsequent antigen-specific T cell response. We hypothesized that cells of the innate immune system, such as natural killer (NK) cells, NK1.1+ T cells (NKT cells), and γ/δ T cells, may regulate the development of allergic airway disease. We demonstrate here that depletion of NK1.1+ cells (NK cells and NKT cells) before immunization inhibits pulmonary eosinophil and CD3+ T cell infiltration as well as in...

  12. SAP-Dependent and -Independent Regulation of Innate T Cell Development Involving SLAMF Receptors.

    Science.gov (United States)

    De Calisto, Jaime; Wang, Ninghai; Wang, Guoxing; Yigit, Burcu; Engel, Pablo; Terhorst, Cox

    2014-01-01

    Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) plays an essential role in the immune system mediating the function of several members of the SLAM family (SLAMF) of receptors, whose expression is essential for T, NK, and B-cell responses. Additionally, the expression of SAP in double-positive thymocytes is mandatory for natural killer T (NKT) cells and, in mouse, for innate CD8(+) T cell development. To date, only two members of the SLAMF of receptors, Slamf1 and Slamf6, have been shown to positively cooperate during NKT cell differentiation in mouse. However, it is less clear whether other members of this family may also participate in the development of these innate T cells. Here, we show that Slamf[1 + 6](-/-) and Slamf[1 + 5 + 6](-/-) B6 mice have ~70% reduction of NKT cells compared to wild-type B6 mice. Unexpectedly, the proportion of innate CD8(+) T cells slightly increased in the Slamf[1 + 5 + 6](-/-) , but not in the Slamf[1 + 6](-/-) strain, suggesting that Slamf5 may function as a negative regulator of innate CD8(+) T cell development. Accordingly, Slamf5(-/-) B6 mice showed an exclusive expansion of innate CD8(+) T cells, but not NKT cells. Interestingly, the SAP-independent Slamf7(-/-) strain showed an expansion of both splenic innate CD8(+) T cells and thymic NKT cells. On the other hand, and similar to what was recently shown in Slamf3(-/-) BALB/c mice, the proportions of thymic promyelocytic leukemia zinc finger (PLZF(hi)) NKT cells and innate CD8(+) T cells significantly increased in the SAP-independent Slamf8(-/-) BALB/c strain. In summary, these results show that NKT and innate CD8(+) T cell development can be regulated in a SAP-dependent and -independent fashion by SLAMF receptors, in which Slamf1, Slamf6, and Slamf8 affect development of NKT cells, and that Slamf5, Slamf7, and Slamf8 affect the development of innate CD8(+) T cells.

  13. A designated centre for people with disabilities operated by The Cheshire Foundation in Ireland, Mayo

    LENUS (Irish Health Repository)

    Hogan, A E

    2011-11-01

    The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKT cells.

  14. Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis.

    LENUS (Irish Health Repository)

    Hogan, A E

    2011-11-01

    The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKT cells.

  15. SAP-independent and -dependent regulation of innate T cell development involving SLAMF receptors

    Directory of Open Access Journals (Sweden)

    Jaime eDe Calisto

    2014-04-01

    Full Text Available Signaling lymphocytic activation molecule (SLAM-associated protein (SAP plays an essential role in the immune system mediating the function of several members of the SLAM family (SLAMF of receptors, whose expression is essential for T, NK, and B cell responses. Additionally, the expression of SAP in double-positive (DP thymocytes is mandatory for natural killer T (NKT cells and, in mouse, for innate CD8+ T cell development. To date, only two members of the SLAMF of receptors, Slamf1 and Slamf6, have been shown to positively cooperate during NKT cell differentiation in mouse. However, it is less clear whether other members of this family may also participate in the development of these innate T cells. Here, we show that Slamf[1+6]-/- and Slamf[1+5+6]-/- B6 mice have an approximately 70% reduction of NKT cells compared to wild-type (WT B6 mice. Unexpectedly, the proportion of innate CD8+ T cells slightly increased in the Slamf[1+5+6]-/-, but not in the Slamf[1+6]-/- strain, suggesting that Slamf5 may function as a negative regulator of innate CD8+ T cell development. Accordingly, Slamf5-/- B6 mice showed an exclusive expansion of innate CD8+ T cells, but not NKT cells. Interestingly, the SAP-independent Slamf7-/- strain showed an expansion of both splenic innate CD8+ T cells and thymic NKT cells. On the other hand, and similar to what was recently shown in Slamf3-/- BALB/c mice, the proportions of thymic PLZFhi NKT cells and innate CD8+ T cells significatively increased in the SAP-independent Slamf8-/- BALB/c strain. In summary, these results show that NKT and innate CD8+ T cell development can be regulated in a SAP-dependent and -independent fashion by SLAMF receptors, in which Slamf1, Slamf6, and Slamf8 affect development of NKT cells, and that Slamf5, Slamf7, and Slamf8 affect the development of innate CD8+ T cells.

  16. Die Schatzkiste

    DEFF Research Database (Denmark)

    Holst-Pedersen, Jette von

    En tekstantologi, tænkt som suppelerende materiale til folkeskolens tyskundervisning i 7.-9. kl.. Die Schatzkiste indeholder tekster i forskellige genrer. Til hver tekst er der formuleret kreative opgaver, der skal motivere til udvikling af elevernes kommunikative færdigheder.......En tekstantologi, tænkt som suppelerende materiale til folkeskolens tyskundervisning i 7.-9. kl.. Die Schatzkiste indeholder tekster i forskellige genrer. Til hver tekst er der formuleret kreative opgaver, der skal motivere til udvikling af elevernes kommunikative færdigheder....

  17. Die Open-Data-Bewegung : Das Verhältnis von Praktiken, Zielen und Selbstbild der Open Knowledge Foundation Deutschland

    NARCIS (Netherlands)

    Baack, Stefan

    2013-01-01

    Open Data bzw. Open Government Data meint den freien Zugang zu und die uneingeschränkt Nutzung und Weiterverbreitung von unbearbeiteten Rohdaten der öffentlichen Verwaltung durch jedermann für jegliche Zwecke. Spätestens seit der Eröffnung des ersten offiziellen Open-Data-Portals Data.gov in den USA

  18. Libanon i regionen

    DEFF Research Database (Denmark)

    Schmidt, Søren

    2011-01-01

    Artiklen behandler Libanons regionale relationer, herunder forholdet til Syrien og Iran. Syrien har gjort krav på Libanon, grebet ind i borgerkrigten, rømmet landet, bevaret agenter og en vis opbakning, er mistænkt i Hariri-sagen, og er senest dybt påvirket af det arabiske forår. Ikke en nem, men...

  19. Simulatorpædagogik

    DEFF Research Database (Denmark)

    Sjøstedt, Peter; Huglstad, Allan

    Formålet med dette working paper er: at definere og afgrænse begreber og emner inden for simulatorstøttet uddannelse, at give anvisninger til undervisere, der anvender simulation og simulator i undervisningen. Publikationen omhandler ikke råd og vejledning af teknisk art. Publikationen er tænkt...

  20. Arkitektur, materialer, teknologi

    DEFF Research Database (Denmark)

    2004-01-01

    En redigeret samling af bidrag til en "tænkt" lærebog om arkitektur, materialer og teknologi, udført af studerende i forbindelse med kursus 0.021. Bygning, produkt og projekt, september 2004. Består af ca. 100 artikler, inddelt efter materialer som tegl, træ, sten, beton, metal, glas, plast...

  1. Early growth response gene-2 (Egr-2 regulates the development of B and T cells.

    Directory of Open Access Journals (Sweden)

    Suling Li

    Full Text Available BACKGROUND: Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development. METHODS AND FINDINGS: The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2(+ lymphocytes resulted in a severe reduction of CD4(+CD8(+ (DP cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow. CONCLUSIONS: Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.

  2. Ein Web-basierter Computergraphik-Kurs im Baukastensystem

    OpenAIRE

    Hönisch, F.; Klein, R.; Straßer, W

    2016-01-01

    Aus der Zusammenfassung: "Dieses Beispiel eines interaktiven Online-Kurses zeigt, wie virtuelle Experimente die traditionellen Lehrmethoden im Bereich der Computergraphik sinnvoll ergänzen. Das Zusammenspiel von Java und dem World-Wide-Web erlaubt die einheitliche Integration von hypertextuellen Vorlesungstexten, interaktiven Visualisierungen, virtuellen Experimenten, Programmierübungen und Programmierschnittstellen in eine unbeschränkt nutzbare virtuelle Lernumgebung."

  3. See This Sound

    DEFF Research Database (Denmark)

    Kristensen, Thomas Bjørnsten

    2009-01-01

    Anmeldelse af udstillingen See This Sound på Lentos Kunstmuseum Linz, Østrig, som markerer den foreløbige kulmination på et samarbejde mellem Lentos Kunstmuseum og Ludwig Boltzmann Institute Media.Art.Research. Udover den konkrete udstilling er samarbejdet tænkt som en ambitiøs, tværfaglig...

  4. Mechanisms of Innate Lymphoid Cell and Natural Killer T Cell Activation during Mucosal Inflammation

    Directory of Open Access Journals (Sweden)

    David Nau

    2014-01-01

    Full Text Available Mucosal surfaces in the airways and the gastrointestinal tract are critical for the interactions of the host with its environment. Due to their abundance at mucosal tissue sites and their powerful immunomodulatory capacities, the role of innate lymphoid cells (ILCs and natural killer T (NKT cells in the maintenance of mucosal tolerance has recently moved into the focus of attention. While NKT cells as well as ILCs utilize distinct transcription factors for their development and lineage diversification, both cell populations can be further divided into three polarized subpopulations reflecting the distinction into Th1, Th2, and Th17 cells in the adaptive immune system. While bystander activation through cytokines mediates the induction of ILC and NKT cell responses, NKT cells become activated also through the engagement of their canonical T cell receptors (TCRs by (glycolipid antigens (cognate recognition presented by the atypical MHC I like molecule CD1d on antigen presenting cells (APCs. As both innate lymphocyte populations influence inflammatory responses due to the explosive release of copious amounts of different cytokines, they might represent interesting targets for clinical intervention. Thus, we will provide an outlook on pathways that might be interesting to evaluate in this context.

  5. SOS

    DEFF Research Database (Denmark)

    Pecseli, Benedicta

    2015-01-01

    Dette støttepapir kan ikke stå alene. Teksten er alene tænkt som en hjælp til gruppearbejdet eller den enkelte midt i skriveprocessen og kan ikke anvendes, hvis man ikke er godt hjemme i grundbøgernes behandling af de samme emner. Det anbefales at følge undervisernes instrukser, anvisninger i gru...

  6. Netbaserede uddannelser og blended learning

    DEFF Research Database (Denmark)

    Bertelsen, Jesper Vedel; Vognsgaard Hjernø, Henriette; Jensen, Michael Peter

    2016-01-01

    Denne håndbog er tænkt som inspiration til uddannelsesfaglige medarbejdere, som er eller skal i gang med at undervise på en netbaseret uddannelse i UCL. Håndbogen giver et teoretisk overblik i forhold til netbaserede uddannelser, online- og blended learning samt en indførsel i hvilke didaktiske...

  7. Den danske kodeks for integritet i forskning

    DEFF Research Database (Denmark)

    Müller Pedersen, Hans; Frøkjær, Sven; Bach, Lise Wogensen;

    forskningsinstitutioner, herunder universiteterne, forskningsrådssystemet, fonde og virksomheder. Den er tænkt som en fælles ramme, der skal implementeres og udvikles på tværs af fagområder. Kodeksen Danish Code of Conduct for Research Integrity er udarbejdet af en arbejdsgruppe nedsat af Uddannelses- og...

  8. Natural killer T cells and non-alcoholic fatty liver disease: Fat chews on the immune system

    Institute of Scientific and Technical Information of China (English)

    Michael Kremer; Ian N Hines

    2008-01-01

    Natural killer T cells (NKT) are an important subset of T lymphocytes. They are unique in their ability to produce both T helper 1 and T helper 2 associated cytokines, thus being capable of steering the immune system into either inflammation or tolerance. Disruption of NKT cell numbers or function results in severe deficits in immune surveillance against pathogens and tumor cells. Growing experimental evidence suggests that hepatosteatosis may reduce resident hepatic as well as peripheral NICE cells. Those models of hepatosteatosis and the change in NKT cell numbers are associated with a disruption of cytokine homeostasis, resulting in a more pronounced release of proinflammatory cytokines which renders the steatotic liver highly susceptible to secondary insults. In this letter to the editor, we focus on recently published data in the World Journal of Gastroenterology by Xu and colleagues demonstrating reduced peripheral NKT ceils in patients with non-alcoholic fatty liver disease, compare those findings with ours and others in different animal models of hepatosteatosis, and hypothesize about the potential underlying mechanism.

  9. Virksomhed og arbejderliv. Bånd, brudflader og bevidsthed på B&W 1850-1920

    DEFF Research Database (Denmark)

    Nielsen, Niels Jul

    2002-01-01

    mange havde tiltænkt den. Bogen sætter desuden fokus på den kapitalistiske virksomheds ledelse. Er det rigtigt, at 1900-tallets ledelsesform erstatter et gammeldags patriarkalsk forhold mellem arbejdsgiveren og de ansatte? Eller er der snarere tale om, at 1800-tallets patriarkalisme er et moderne svar...

  10. Effiziente Finite-Element-Modellierung gekoppelter starrer und flexibler Strukturbereiche bei transienten Einwirkungen [online].

    OpenAIRE

    Goettlicher, Burkhard

    2007-01-01

    Kurzfassung Die Kombination komplizierter Geometrien und Randbedingungen, aufwendiger Materialmodelle sowie der Wunsch nach hoher Berechnungsgenauigkeit führen insbesondere bei der Simulation transienter Vorgänge in der Strukturmechanik auf anspruchsvolle numerische Modelle mit sehr vielen Freiheitsgraden. Der dabei erforderliche hohe numerische Berechnungsaufwand schränkt die Anwendungen oft ein, insbesondere Langzeituntersuchungen bei transienter Belastung können ka...

  11. Making Light Rail Mobilities

    DEFF Research Database (Denmark)

    Olesen, Mette

    Denne Ph.d. afhandling bidrager med et kvalitativt perspektiv på letbaner som et strategisk byudviklingsværktøj i middelstore Europæiske byer (100.000- 350.000 indbyggere). Afhandlingen skal ses som et bidrag til debatten om letbanesystemer og er tiltænkt som et supplement til de mere tekniske og...

  12. Tagboliger - kom godt i gang

    DEFF Research Database (Denmark)

    Hansen, Ernst Jan de Place; Pingel, Erik

    2010-01-01

    Denne pjece er tænkt som en inspiration for alle der går med overvejelser om at etablere tagboliger, uanset om det er i ældre ejendomme med et uudnyttet loft eller på en ejendom med fladt tag, som trænger til udskiftning. Det kan være boligejere, eller andels- og ejerboligforeningsbestyrelser....

  13. En ansats til en teori om Situationel Dialektisk Ledelse

    DEFF Research Database (Denmark)

    Dakwar, Julia Rytter; Lorentzen, Anne-Christine Rosfeldt; Smedegaard, Flemming

    2015-01-01

    I denne artikel argumenteres der for, at der er behov for et nyt ledelsesparadigme, som døbes Situa-tionel Dialektisk Ledelse. Hovedudgangspunktet for tankerne bag den nye teori er dialektisk teori, som suppleres med inspira-tion fra vidt forskellige teorier, der ikke før har været tænkt sammen, ...

  14. Vitamin D and 1,25(OH2D Regulation of T cells

    Directory of Open Access Journals (Sweden)

    Margherita T. Cantorna

    2015-04-01

    Full Text Available Vitamin D is a direct and indirect regulator of T cells. The mechanisms by which vitamin D directly regulates T cells are reviewed and new primary data on the effects of 1,25 dihydroxyvitamin D (1,25(OH2D on human invariant natural killer (iNKT cells is presented. The in vivo effects of vitamin D on murine T cells include inhibition of T cell proliferation, inhibition of IFN-γ, IL-17 and induction of IL-4. Experiments in mice demonstrate that the effectiveness of 1,25(OH2D requires NKT cells, IL-10, the IL-10R and IL-4. Comparisons of mouse and human T cells show that 1,25(OH2D inhibits IL-17 and IFN-γ, and induces T regulatory cells and IL-4. IL-4 was induced by 1,25(OH2D in mouse and human iNKT cells. Activation for 72h was required for optimal expression of the vitamin D receptor (VDR in human and mouse T and iNKT cells. In addition, T cells are potential autocrine sources of 1,25(OH2D but again only 48–72h after activation. Together the data support the late effects of vitamin D on diseases like inflammatory bowel disease and multiple sclerosis where reducing IL-17 and IFN-γ, while inducing IL-4 and IL-10, would be beneficial.

  15. Research progress on natural killer T cells in host defence against intracellular bacterial infectious diseases%自然杀伤T细胞抗胞内菌感染的研究进展

    Institute of Scientific and Technical Information of China (English)

    孔晓明; 刘勇

    2011-01-01

    自然杀伤T细胞(NKT细胞)是免疫细胞中一类具有特定标记的T细胞亚群,能特异性识别南抗原呈递细胞表面CD1d分子所呈递的糖脂类抗原.活化后的NKT细胞能分泌多种细胞因子,参与机体的天然免疫和获得性免疫反应,还能直接杀伤靶细胞,具有效应细胞的功能.研究发现,NKT细胞在抗胞内菌感染中发挥着重要作用.%Natural killer T cells (NKT cells) are a unique subset of mature T lymphocytes that can recognize " glycolipids presented by CDld molecules expressed on antigen-presenting cells through cell recognition pathway. After activation, NKT cells can secrete large amounts of cytokines, which play important roles in innate and acquired immune responses. NKT cells can also act as direct effector cells via cytolysis or granulysin. Studies have shown that NKT cells play an important role in anti-intracellular bacterial infection.

  16. Activation of natural killer T Cells promotes M2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signalling axis in obesity

    NARCIS (Netherlands)

    Ji, Y.; Sun, S.; Xu, Aimin; Bhargava, P.; Yang, Liu; Lam, K.S.L.; Gao, Bin; Lee, Chih-Hao; Kersten, A.H.; Qi, L.

    2012-01-01

    Natural killer T (NKT) cells are important therapeutic targets in various disease models and are under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type

  17. Byzantine Neumes

    DEFF Research Database (Denmark)

    Troelsgård, Christian

    musikeksempler med transskription til moderne linjenotation og en detaljeret bibliografi. Bogen er tænkt som en opdatering og uddybning af H.J.W. Tillyards Handbook of the Middle Byzantine Musical Notation (København 1935), en af de første udgivelser i serien Monumenta Musicae Byzantinae. Udgivelsen opsummerer...

  18. Ekspertvirke i organisatorisk kontekst

    DEFF Research Database (Denmark)

    Møller, Bjarke Grønbæk

    2015-01-01

    Kapitlet diskuterer fænomenet ekspertise relateret til en organisatorisk kontekst. Kapitlet er tænkt som en refleksionskilde, der har til formål at kaste lys over, hvordan ekspertise kan forstås, når fænomenet skal ”udfolde” sig i vores organisatoriske hverdagsliv. Med ovennævnte betragtning bliv...

  19. Vandforvaltning og vandplanlægning

    DEFF Research Database (Denmark)

    Baaner, Lasse

    indsatsprogrammer lider af en del mangler i forhold til at opfylde direktivets krav. Analyserne viser også, at integrationen af lovgivningen vedrørende grundvandsbeskyttelse ikke er vellykket, og på den baggrund anbefales lovgivningen gentænkt med henblik på at etablere en sårbarhedsdifferentieret regulering af...

  20. Trækonstruktioner

    DEFF Research Database (Denmark)

    Larsen, H.J.; Riberholt, H.

    Denne anvisning behandler forbindelser i trækonstruktioner i henhold til de normer for bærende konstruktioner, der er udkommet i 1982. Den knytter sig til SBI-anvisning 135: Trækonstruktioner, Beregning. Anvisningen er tænkt anvendt både af projekterende og som lærebog på ingeniørskolerne....

  1. Innate immunity drives the initiation of a murine model of primary biliary cirrhosis.

    Directory of Open Access Journals (Sweden)

    Chao-Hsuan Chang

    Full Text Available Invariant natural killer T (iNKT cells play complex roles in bridging innate and adaptive immunity by engaging with glycolipid antigens presented by CD1d. Our earlier work suggested that iNKT cells were involved in the initiation of the original loss of tolerance in primary biliary cirrhosis (PBC. To address this issue in more detail and, in particular, to focus on whether iNKT cells activated by a Th2-biasing agonist (2s,3s,4r-1-O-(α-D-galactopyranosyl-N-tetracosanoyl-2-amino-1,3,4-nonanetriol (OCH, can influence the development of PBC in a xenobiotic-induced PBC murine model. Groups of mice were treated with either OCH or, as a control, α-galactosylceramide (α-GalCer and thence serially followed for cytokine production, markers of T cell activation, liver histopathology and anti-mitochondrial antibody responses. Further, additional groups of CD1d deleted mice were similarly studied. Our data indicate that administration of OCH has a dramatic influence with exacerbation of portal inflammation and hepatic fibrosis similar to mice treated with α-GalCer. Further, iNKT cell deficient CD1d knockout mice have decreased inflammatory portal cell infiltrates and reduced anti-mitochondrial antibody responses. We submit that activation of iNKT cells can occur via overlapping and/or promiscuous pathways and highlight the critical role of innate immunity in the natural history of autoimmune cholangitis. These data have implications for humans with PBC and emphasize that therapeutic strategies must focus not only on suppressing adaptive responses, but also innate immunity.

  2. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system.

    Science.gov (United States)

    Montalvillo, Enrique; Garrote, José Antonio; Bernardo, David; Arranz, Eduardo

    2014-05-01

    The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity.Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  3. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system

    Directory of Open Access Journals (Sweden)

    Enrique Montalvillo

    2014-05-01

    Full Text Available The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity. Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  4. Changes in the Antioxidant Systems as Part of the Signaling Pathway Responsible for the Programmed Cell Death Activated by Nitric Oxide and Reactive Oxygen Species in Tobacco Bright-Yellow 2 Cells1

    Science.gov (United States)

    de Pinto, Maria Concetta; Tommasi, Franca; De Gara, Laura

    2002-01-01

    Nitric oxide (NO) has been postulated to be required, together with reactive oxygen species (ROS), for the activation of the hypersensitive reaction, a defense response induced in the noncompatible plant-pathogen interaction. However, its involvement in activating programmed cell death (PCD) in plant cells has been questioned. In this paper, the involvement of the cellular antioxidant metabolism in the signal transduction triggered by these bioactive molecules has been investigated. NO and ROS levels were singularly or simultaneously increased in tobacco (Nicotiana tabacum cv Bright-Yellow 2) cells by the addition to the culture medium of NO and/or ROS generators. The individual increase in NO or ROS had different effects on the studied parameters than the simultaneous increase in the two reactive species. NO generation did not cause an increase in phenylalanine ammonia-lyase (PAL) activity or induction of cellular death. It only induced minor changes in ascorbate (ASC) and glutathione (GSH) metabolisms. An increase in ROS induced oxidative stress in the cells, causing an oxidation of the ASC and GSH redox pairs; however, it had no effect on PAL activity and did not induce cell death when it was generated at low concentrations. In contrast, the simultaneous increase of NO and ROS activated a process of death with the typical cytological and biochemical features of hypersensitive PCD and a remarkable rise in PAL activity. Under the simultaneous generation of NO and ROS, the cellular antioxidant capabilities were also suppressed. The involvement of ASC and GSH as part of the transduction pathway leading to PCD is discussed. PMID:12376637

  5. Production of Reactive Oxygen Species, Alteration of Cytosolic Ascorbate Peroxidase, and Impairment of Mitochondrial Metabolism Are Early Events in Heat Shock-Induced Programmed Cell Death in Tobacco Bright-Yellow 2 Cells1

    Science.gov (United States)

    Vacca, Rosa Anna; de Pinto, Maria Concetta; Valenti, Daniela; Passarella, Salvatore; Marra, Ersilia; De Gara, Laura

    2004-01-01

    To gain some insight into the mechanisms by which plant cells die as a result of abiotic stress, we exposed tobacco (Nicotiana tabacum) Bright-Yellow 2 cells to heat shock and investigated cell survival as a function of time after heat shock induction. Heat treatment at 55°C triggered processes leading to programmed cell death (PCD) that was complete after 72 h. In the early phase, cells undergoing PCD showed an immediate burst in hydrogen peroxide (H2O2) and superoxide (O2·-) anion production. Consistently, death was prevented by the antioxidants ascorbate (ASC) and superoxide dismutase (SOD). Actinomycin D and cycloheximide, inhibitors of transcription and translation, respectively, also prevented cell death, but with a lower efficiency. Induction of PCD resulted in gradual oxidation of endogenous ASC; this was accompanied by a decrease in both the amount and the specific activity of the cytosolic ASC peroxidase (cAPX). A reduction in cAPX gene expression was also found in the late PCD phase. Moreover, changes of cAPX kinetic properties were found in PCD cells. Production of ROS in PCD cells was accompanied by early inhibition of glucose (Glc) oxidation, with a strong impairment of mitochondrial function as shown by an increase in cellular NAD(P)H fluorescence, and by failure of mitochondria isolated from cells undergoing PCD to generate membrane potential and to oxidize succinate in a manner controlled by ADP. Thus, we propose that in the early phase of tobacco Bright-Yellow 2 cell PCD, ROS production occurs, perhaps because of damage of the cell antioxidant system, with impairment of the mitochondrial oxidative phosphorylation. PMID:15020761

  6. Use of plasma C-reactive protein, procalcitonin, neutrophils,macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Andersen, Ove; Kronborg, Gitte;

    2007-01-01

    parallel with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed – one including a linear combination of the three best performing markers and another including all six – and the area under the receiver operating characteristic...

  7. Core 2 ß1,6-N-acetylglucosaminyltransferase-I, crucial for P-selectin ligand expression is controlled by a distal enhancer regulated by STAT4 and T-bet in CD4+ T helper cells 1.

    Science.gov (United States)

    Mardahl, Maibritt; Schröter, Micha F; Engelbert, Dirk; Pink, Matthias; Sperandio, Markus; Hamann, Alf; Syrbe, Uta

    2016-09-01

    P-selectin ligands (P-ligs) support the recruitment of lymphocytes into inflamed tissues. Binding to P-selectin is mediated by oligosaccharide groups synthesized by means of several glycosyltransferases including core 2 ß1,6-N-acetylglucosaminyltransferase-I (C2GlcNAcT-I), encoded by the gene Gcnt1. Using Gcnt1(-/-) Th1 cells, we show that C2GlcNAcT-I is crucial for inflammatory T cell homing in vivo. To understand the molecular regulation of Gcnt1 in CD4(+) T helper cells, we performed ChIP-on-chip experiments across the Gcnt1 locus assessing the chromatin structure in P-lig-expressing versus non-expressing CD4(+) T cells. This identified a distal region about 20kb upstream of the promoter where the presence of a H3K27me3 mark correlated with Gcnt1 repression. This region possessed IL-12-dependent enhancer activity in reporter assays, in accordance with preferential IL-12-dependent induction of Gcnt1 in vitro. STAT4 and T-bet cooperated in control of the enhancer activity. Deficiency in either one resulted in drastically reduced Gcnt1 mRNA expression in differentiated Th1 cells. While both STAT4 and T-bet were bound to the enhancer early after activation only T-bet binding persisted throughout the expansion phase after TCR signal cessation. This suggests sequential action of STAT4 and T-bet at the enhancer. In summary, we show that Gcnt1 transcription and subsequent P-lig induction in Th1 cells is governed by binding of STAT4 and T-bet to a distal enhancer and further regulated by epigenetic marks such as H3K27me3.

  8. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Andersen, Ove; Kronborg, Gitte;

    2007-01-01

    Accurate and timely diagnosis of community-acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared the diagnost...

  9. Alkoxide routes to Inorganic Materials

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, George H [ORNL

    2007-12-01

    An all alkoxide solution chemistry utilizing metal 2-methoxyethoxide complexes in 2-methoxyethanol was used to deposit thin-films of metal oxides on single-crystal metal oxide substrates and on biaxially textured metal substrates. This same chemistry was used to synthesize complex metal oxide nanoparticles. Nuclear Magnetic Resonance spectroscopy was used to study precursor solutions of the alkaline niobates and tantalates. Film crystallization temperatures were determined from x-ray diffraction patterns of powders derived from the metal oxide precursor solutions. Film structure was determined via x-ray diffraction. Film morphology was studied using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Epitaxial thin-films of strontium bismuth tantalate (SrBi{sub 2}Ta{sub 2}O{sub 9}, SBT) and strontium bismuth niobate (SrBi{sub 2}Nb{sub 2}O{sub 9}, SBN) were deposited on single crystal [1 0 0] magnesium oxide (MgO) buffered with lanthanum manganate (LaMnO{sub 3}, LMO). Epitaxial thin films of LMO were deposited on single crystal [100] MgO via Rf-magnetron sputtering and on single crysal [100] lanthanum aluminate (LaAlO{sub 3}) via the chemical solution deposition technique. Epitaxial thin-films of sodium potassium tantalate (na{sub 0.5}K{sub 0.5}TaO{sub 3}, NKT), sodium potassium niobate (Na{sub 0.5}K{sub 0.5}NbO{sub 3}, NKN) and sodium potassium tantalum niobate (Na{sub 0.5}K{sub 0.5}Ta{sub 0.5}O{sub 3}, NKTN) were deposited on single crystal [1 0 0] lanthanum aluminate and [1 0 0] MgO substrates (NKT and NKN) and biaxially textured metal substrates via the chemical solution deposition technique. Epitaxial growth of thin-films of NKT, NKN and NKTN was observed on LAO and Ni-5% W. Epitaxial growth of thin-films of NKN and the growth of c-axis aligned thin-films of NKT was observed on MgO. Nanoparticles of SBT, SBN, NKT and NKN were synthesized in reverse micelles from alkoxide precursor solutions. X-ray diffraction and transmission electron

  10. The Roles of Innate Immune Cells in Liver Injury and Regeneration

    Institute of Scientific and Technical Information of China (English)

    Zhongjun Dong; Haiming Wei; Rui Sun; Zhigang Tian

    2007-01-01

    For predominant abundance with liver-specific Kupffer cells, natural killer (NK) cells, and natural killer T (NKT)cells and their rapid responses to several stimuli, the liver is considered as an organ with innate immune features.In contrast to their roles in the defense of many infectious agents like hepatitis viruses and parasites, hepatic innate immune cells are also involved in the immunopathogenesis of human clinical liver diseases and several murine hepatitis models such as concanavalin A (Con A), lipopolysaccharide (LPS), or polyinosinic-polycytidylic acid (Poly I:C)-induced liver injury. In this review, the destructive roles of NK cells, NKT cells and Kupffer cells in the processes of immune-mediated liver injury and regeneration will be discussed, and some putative mechanisms involving the impairment of liver regeneration caused by activated hepatic innate immune cells are also proposed.

  11. Lægestudiet reduceret til lektielæsning

    DEFF Research Database (Denmark)

    Okkels, Niels

    2013-01-01

    Lægeuddannelsen lider under et ’kontrol og måle’-regime, som får lærelysten til at drukne i mistillid og bureaukrati. Resultatet kan blive læger, som aldrig har tænkt en selvstændig tanke, men bare har gjort, som der stod i målfortegnelsen......Lægeuddannelsen lider under et ’kontrol og måle’-regime, som får lærelysten til at drukne i mistillid og bureaukrati. Resultatet kan blive læger, som aldrig har tænkt en selvstændig tanke, men bare har gjort, som der stod i målfortegnelsen...

  12. Serious Games

    DEFF Research Database (Denmark)

    Christensen, Jens

    Serious Games er et nyt it-forretningsområde, der siden årtusindskiftet er vokset frem, først i USA og dernæst i Vesteuropa og and i-lande. Til forskel fra computerspil er serious games ikke underholdning, men tænkt som et værktøj til støtte for statens og erhvervslivets forskellige funktioner. D...

  13. Dynamik bildungsrelevanter Informationsumwelten

    OpenAIRE

    Hesse, Friedrich W

    2008-01-01

    Der Begriff der "Informationsgesellschaft" ist in den letzten Jahren von einem Schlagwort zu einer adäquaten Beschreibung gesellschaftlicher Realität gewachsen. Insbesondere durch das Internet werden vormals getrennte "Informationswelten" (Schulen, Hochschulen, Massenmedien, Museen etc.) stärker verknüpft als jemals zuvor. Aus Sicht der Nutzer ist Bildung nicht mehr auf institutionalisierte Lernformen und klassische Lernorte (Schule, Hochschule) beschränkt, sondern untrennbar verbunden mit As...

  14. Pathogens in free-ranging African carnivores

    OpenAIRE

    Goller, Katja Verena

    2011-01-01

    Die ökologische Rolle der meisten Wildtier-Pathogene in Bezug zur langfristigen Populationsdynamik ihrer Wirte ist nur ansatzweise erforscht und wird deshalb nur unzureichend verstanden. Stattdessen ist die Erforschung von Infektionen mit Pathogenen oft beschränkt auf einzelne Fallstudien oder auf Perioden mit deutlich erhöhten Mortalitätsraten innerhalb der Wirtspopulation. Pathogene mit geringer Virulenz können jedoch durch synergistisches Auftreten verheerende Auswirkungen auf die Fitness ...

  15. Krigsredaktører

    DEFF Research Database (Denmark)

    Jørndrup, Hanne; Rohleder, Niels

    2013-01-01

    -læggelse. Hvilke krige skal dækkes, hvem skal sendes til krigszonen, hvordan får man adgang til og viden om konflikten, hvem samarbejder man med og hvad gør man af de indhentede erfarin-ger? Interviewene viser, hvordan krigsdækningen bliver tænkt ind i de vante rutiner og gøres til et element i mediernes interne...

  16. Den Danske Netordbog

    DEFF Research Database (Denmark)

    Bergenholtz, Henning; Vrang, Vibeke; Almind, Richard;

    Denne danske ordbog er primært tænkt som hjælpeværktøj i forbindelse med tvivl og usikkerhed, når man skriver en dansk tekst. Den Danske Netordbog er en yderst omfattende ordbog med mere end 110.000 forskellige opslagsord og en lang række oplysninger, herunder grammatik, betydning, synonym (ord m...

  17. Protective mucosal immunity mediated by epithelial CD1d and IL-10

    OpenAIRE

    Olszak, Torsten; Neves, Joana F.; Dowds, C. Marie; Baker, Kristi; Glickman, Jonathan; Davidson, Nicholas O; Lin, Chyuan-Sheng; Jobin, Christian; Brand, Stephan; Sotlar, Karl; Wada, Koichiro; Katayama, Kazufumi; Nakajima, Atsushi; Mizuguchi, Hiroyuki; Kawasaki, Kunito

    2014-01-01

    The mechanisms by which mucosal homeostasis is maintained are of central importance to inflammatory bowel disease. Critical to these processes is the intestinal epithelial cell (IEC), which regulates immune responses at the interface between the commensal microbiota and the host1,2. CD1d presents self and microbial lipid antigens to natural killer T (NKT) cells, which are involved in the pathogenesis of colitis in animal models and human inflammatory bowel disease3–8. As CD1d crosslinking on ...

  18. Freisetzung von Neonicotinoiden aus der Saatgutbeizung in Guttation von Kulturpflanzen und deren Auswirkungen auf Honigbienen Apis mellifera L. (Hymenoptera: Apidae)

    OpenAIRE

    Reetz, Jana E.

    2015-01-01

    Die Saatgutbeizung mit Clothianidin, Imidacloprid und Thiamethoxam (Neonicotinoide) stellte ein Applikationsverfahren im Pflanzenschutz dar, von dem bislang kein Risiko gegenüber Nicht-Zielorganismen angenommen wurde. Nach den akuten Bienenschäden im Rheintal 2008 ruht in Deutschland die Zulassung der Wirkstoffe zur Saatgutbeizung in Mais und Getreide; seit Mai 2013 ist die Anwendung weiter eingeschränkt (Durchführungs-VO (EU) Nr. 485/2013). Die von Pflanzen periodisch abgesonderte Guttation ...

  19. Protektive Effekte des ER Chaperons GRP78 in der Doxorubizinkardiotoxizität

    OpenAIRE

    Tscheschner, Henrike

    2015-01-01

    Das Anthrazyklin Doxorubizin ist eines der am häufigsten verwendeten Chemotherapeutika. Es wird allerdings in seiner Anwendung durch seine Kardiotoxizität, mit der Gefahr der Entwicklung einer ernsten Herzinsuffizienz, eingeschränkt. Da bislang nur eine symptomatische Therapie der Doxorubizinkardiomyopathie möglich ist, liegt der Fokus auf der Vermeidung hoher Doxorubizindosen. Die einzige präventive Therapie ist für ein großes Patientenkollektiv, Kinder und Jugendliche, nicht geeignet. Daher...

  20. α-Galactosylceramide protects swine against influenza infection when administered as a vaccine adjuvant

    OpenAIRE

    Bianca L. Artiaga; Guan Yang; Hackmann, Timothy J.; Qinfang Liu; Richt, Jürgen A.; Shahram Salek-Ardakani; Castleman, William L.; Lednicky, John A.; Driver, John P.

    2016-01-01

    Natural killer T (NKT) -cells activated with the glycolipid ligand α-galactosylceramide (α-GalCer) stimulate a wide array of immune responses with many promising immunotherapeutic applications, including the enhancement of vaccines against infectious diseases and cancer. In the current study, we evaluated whether α-GalCer generates protective immunity against a swine influenza (SI) virus infection when applied as an intramuscular vaccine adjuvant. Immunization of newly weaned piglets with UV-...

  1. Uddannelse og Entrepreneurship

    DEFF Research Database (Denmark)

    Blenker, Per; Dreisler, Poul; Færgemann, Helle Maibom;

    2004-01-01

    Innovation og entrepreneurship står højt på den politiske dagsorden og universiteterne er tiltænkt en central rolle i denne proces, hvis mål er at skabe større vækst og øget velfærd i samfundet. Et af midlerne har været at motivere til større samarbejde om forskning og uddannelse i samspil mellem...

  2. Passive und aktive Immunisierung gegen Enterokokken-Aggregationssubstanz: Testung der protektiven Wirkung in murinen Infektionsmodellen

    OpenAIRE

    Woll, Arne

    2006-01-01

    Hintergrund: Nosokomial erworbene Enterokokken-Infektionen sind eine zunehmende Bedrohung für Intensivpatienten und immunsupprimierte Patienten. Die Letalität von Enterokokken-Bakteriämien wird mit über 40 % beziffert und die Therapie–Optionen sind insbesondere bei multiresistenten Enterokokken deutlich eingeschränkt. Die Zunahme multiresistenter Enterokokkenstämme erfordert ein Umdenken und das Erarbeiten möglicher Alternativen. Das Enterokokken-Oberflächenprotein Aggregation Substance (AS) ...

  3. Functions of Thymic Stromal Lymphopoietin in Immunity and Disease

    OpenAIRE

    Zhang, Yanlu; Zhou, Baohua

    2012-01-01

    Thymic stromal lymphopoietin (TSLP) is an interleukin 7 (IL-7)-like cytokine expressed mainly by epithelial cells. Current studies provide compelling evidence that TSLP is capable of activating dendritic cells (DCs) to promote T helper (Th) 2 immune responses. TSLP has also been shown to directly promote Th2 differentiation of naïve CD4+ T cell, and activate natural killer T (NKT) cells, basophils and other innate immune cells at the initial stage of inflammation. In addition, TSLP affects B ...

  4. Ejakulatgewinnung und Ejakulatanalyse bei Krallenaffen (Callitrichidae; Platyrrhini; Primates)

    OpenAIRE

    Schneiders, Alexander

    2005-01-01

    Die Verfügbarkeit ausreichender Mengen von Spermatozoen guter Qualität ist ein Faktor, der die reproduktionsbiologische Forschung sowie die Entwicklung assistierender Reproduktionstechniken bei Primaten stark einschränkt. Als Routinemethode bei Primaten gilt die Elektroejakulation unter Verwendung von Rektalsonden (rectal probe electroejaculation, RPE). Insbesondere bei den größeren Altweltaffen ist die RPE oft angewendet worden. Aufgrund ihrer geringen Körpergröße ist die RPE bei den kleinen...

  5. Der Einfluss von Hyaluronan auf die Synthese von Fibrinolysefaktoren in humanen peritonealen Mesothelzellen

    OpenAIRE

    Sauter, Matthias

    2004-01-01

    Die Peritonealdialyse ist neben der Hämodialyse ein häufig genutztes Verfahren zur Nierenersatztherapie. Diese Methode wird jedoch oft durch intraperitoneale Fibrinablagerungen verschiedener Ursachen (gravierende homöostatische Störungen, Peritonitiden, Fremdmaterialien, ...) eingeschränkt. Wesentlich in der Pathogenese solcher Ablagerungen sind Störungen des fibrinolytischen Gleichgewichts. Mesothelzellen synthetisieren mit t-PA und PAI-1 die Faktoren, deren Gleichgewicht in der Peritonealhö...

  6. Differential expression of NK receptors CD94 and NKG2A by T cells in rheumatoid arthritis patients in remission compared to active disease.

    LENUS (Irish Health Repository)

    Walsh, Ceara E

    2011-01-01

    TNF inhibitors (TNFi) have revolutionised the treatment of rheumatoid arthritis (RA). Natural killer (NK) cells and Natural Killer Cell Receptor+ T (NKT) cells comprise important effector lymphocytes whose activity is tightly regulated through surface NK receptors (NKRs). Dysregulation of NKRs in patients with autoimmune diseases has been shown, however little is known regarding NKRs expression in patients with TNFi-induced remission and in those who maintain remission vs disease flare following TNFi withdrawal.

  7. Arbeit und Beschäftigung für Menschen mit chronischen psychischen Erkrankungen im Spannungsfeld zwischen Inklusion und Exklusion : überarb. Version

    OpenAIRE

    Dornseifer, Anja

    2013-01-01

    Menschen mit Behinderungen sind besonders hohen Risiken im Erwerbsleben ausgesetzt. Dies betrifft insbesondere auch Menschen mit chronischen psychischen Erkrankungen. Insgesamt ist ihre Teilhabe am Arbeitsmarkt stark eingeschränkt. Im Vergleich mit der allgemeinen Arbeitslosenquote liegt die Arbeitslosenquote von schwerbehinderten Menschen deutlich höher und dementsprechend ist die Erwerbsquote von Menschen mit Behinderungen deutlich geringer als die allgemeine Erwerbsquote. Darüber hinaus st...

  8. Wandel in der Implementation des Deutschen Embryonenschutzgesetzes

    OpenAIRE

    Bals-Pratsch M; Dittrich R; Frommel M

    2010-01-01

    Das Embryonenschutzgesetz (ESchG) bildet seit 1990 die rechtliche Grundlage für die Fortpflanzungmedizin in Deutschland. Die Bundesärztekammer (BÄK) hat aus diesem Gesetz (§ 1 Abs. 1 Nr. 3 und 5) die sogenannte Dreierregel herausgelesen. Damit hat sie zwar durch die Begrenzung des Transfers auf 3 Embryonen den Gesundheitsschutz der Frau hervorgehoben, gleichzeitig aber die reproduktiven Rechte der Frau eingeschränkt. Da die Fortschritte in der Reproduktionsmedizin, wie die Blastozystenkult...

  9. Mere kvalificeret studievalg – mindre frafald?

    DEFF Research Database (Denmark)

    Heilesen, Simon

    2015-01-01

    Artiklen redegør for to forsøg med at anvende MOOC-formatet (Massive Open Online Course) i en dansk, regional sammenhæng. Forsøgene er tænkt som et bud på en mulig vej til at nedbringe studiefrafald gennem bedre information på ungdomsuddannelserne om, hvad et universitetsstudium indebærer. De to...

  10. Funktionalisierung organischer Verbindungen durch Borylentransfer

    OpenAIRE

    Herbst, Thomas

    2009-01-01

    Im Rahmen dieser Arbeit wurden Gruppe 6 Aminoborylenkomplexe zum Borylentransfer auf Alkine verwendet. Die Bor–Übergangsmetallmehrfachbindung wird gespalten, und die Boryleneinheit (BR) auf die C-C-Dreifachbindung übertragen. Diese formale [2+1]-Cycloaddition macht Borirene (Boracyclopropene) in sehr guten Ausbeuten zugänglich. In früheren Arbeiten ist die Borirensynthese entweder auf geringe Ausbeuten oder auf wenige Beispiele mit schwer zugänglichen Edukten beschränkt. Die entwickelte Metho...

  11. Die paradoxe Hirnembolie : Diagnosestellung und Langzeitverlauf

    OpenAIRE

    Jauß, Jan Marek

    2003-01-01

    Eine paradoxe Embolie kommt als Schlaganfallätiologie in Frage, wenn ein kardialer Rechts-Links-Shunt diagnostiziert wurde und andere Ursachen ausgeschlossen wurden. Die Diagnosestellung erfolgte bisher durch transösophageale Echokardiographie (TEE) und war in der Frühphase nach Hirninfarkt nur einge-schränkt möglich. In der vorliegenden Arbeit wird daher ein einfaches, nicht-invasives Untersuchungsverfahren mit transkranieller Dopplersonographie und nicht-lungengängigem Ultraschallkontra...

  12. Störung der Demokratie: der Europäische Gerichtshof engt den Spielraum der Regierungen ein

    OpenAIRE

    Höpner, M.

    2009-01-01

    Der Europäische Gerichtshof greift zunehmend in Rechtsbestände ein, die eigentlich in den Zuständigkeitsbereich der Mitgliedstaaten fallen. Neben die politische Integration durch Vertragsschlüsse und Richtlinien hat sich eine „Integration durch Recht“ geschoben, die zunehmend an politischer Brisanz gewinnt. Der Handlungsspielraum auf nationaler Ebene wird eingeschränkt, ohne dass auf kurze bis mittlere Sicht neue Gestaltungsoptionen marktkorrigierender Politik auf europäischer Ebene eröffnet ...

  13. Eine neuartige Roboterkinematik für die laparoskopische Single-Port Chirurgie

    OpenAIRE

    Sanagoo, Arash

    2015-01-01

    Minimal invasive Operationstechniken haben sich in den letzten Jahren sehr schnell weiterentwickelt. Unter anderem konnte sich die roboterassistierte Laparoskopie auf dem Markt etablieren. Solche Systeme können jedoch sehr eingeschränkt für die Single-Port Laparoskopie eingesetzt werden. Im Rahmen dieser Arbeit wurde basierend auf einer sphärischen Parallelkinematik ein kompakter Manipulator entwickelt. Dieser Manipulator wird in erster Linie für die laparoskopische Single-Port Chirurgie g...

  14. Gastrointestinal lymphomas: Morphology, immunophenotype and molecular features

    OpenAIRE

    Bautista-Quach, Marnelli A; Ake, Christopher D.; Chen, Mingyi; Wang, Jun

    2012-01-01

    Primary gastrointestinal lymphoma comprises 10-15% of all non-Hodgkin lymphomas and encompasses 30-40% of the total extranodal lymphomas. Approximately 60-75% of cases occur in the stomach, and then the small bowel, ileum, cecum, colon and rectum. Lymphoid neoplasms may consist of mature B, T and less commonly extranodal NK/T cells. Of these, the two most frequently encountered histologic subtypes are extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), wher...

  15. Oral administration of immunoglobulin G-enhanced colostrum alleviates insulin resistance and liver injury and is associated with alterations in natural killer T cells.

    Science.gov (United States)

    Adar, T; Ben Ya'acov, A; Lalazar, G; Lichtenstein, Y; Nahman, D; Mizrahi, M; Wong, V; Muller, B; Rawlin, G; Ilan, Y

    2012-02-01

    Insulin resistance and metabolic syndrome are chronic inflammatory conditions that lead to hepatic injury and non-alcoholic steatohepatitis (NASH). Bovine colostrum has therapeutic effects in a variety of chronic infections. However its effectiveness in NASH was never studied. Natural killer T (NKT) cells have been shown to be associated with some of the pathological and metabolic abnormalities accompanying NASH in leptin-deficient (ob/ob) mice. In the present study, we used hyperimmune bovine colostrum to treat hepatic injury and insulin resistance and we also assessed the effects on NKT cells. We used ob/ob mice that were fed for 6 weeks with either 0·1 mg bovine colostrum prepared from non-immunized cows, 0·1 mg hyperimmune colostrum raised against a bacterial lipopolysaccharide (LPS) extract or 0·001, 0·1 or 1 mg of immunoglobulin (Ig)G purified from hyperimmune colostrum (IgG-LPS). NKT cells were phenotyped by flow cytometry, and hepatic injury and insulin resistance were assessed by measuring fasting glucose levels, glucose tolerance tests and liver enzymes. Fat accumulation was measured in the liver and plasma. Oral administration of hyperimmune colostrums decreased alanine aminotransferase (ALT) serum levels and serum triglycerides compared to controls. Glucose intolerance was also improved by the hyperimmune colostrum preparations. These results were accompanied by a decrease in serum tumour necrosis factor (TNF)-α levels following oral treatment with 0·1 or 1 mg of IgG-LPS. The beneficial effects of hyperimmune colostrums were associated with an increase in the number of splenic NKT cells. These data suggest that oral administration of hyperimmune colostrum preparations can alleviate chronic inflammation, liver injury and insulin resistance associated with NASH. PMID:22236001

  16. Phasengleichgerichtete Signalmittelung der Kardiotokographie bei intrauteriner Wachstumsretardierung

    OpenAIRE

    Huhn, Evelyn Annegret

    2007-01-01

    Die Variabilität der fetalen Herzfrequenz ist bei intrauteriner Wachtumsretardierung (IUWR) eingeschränkt. Eine Abnahme im Verlauf der Schwangerschaft wird als ein Zeichen einer akuten Gefährdung des Feten angesehen. Im Rahmen der vorliegenden Arbeit wird eine neue Methode, die phasengleichgerichtete Signalmittelung (PRSA), anhand von Ruhe-Kardiotokogrammen von 74 wachstumsretardierten und 161 normalen Feten getestet. Die Methode analysiert Tachogramme vor und nach Beschleunigungen der Herzfr...

  17. Wenn Fremde Fremden begegnen : zur Darstellung von Indifferenz im modernen Alltag

    OpenAIRE

    Reuter, Julia

    2002-01-01

    'Die Figur des Fremden wird in der Soziologie klassischerweise auf den außeralltäglichen Randseiter beschränkt, der krisenhafte Begegnungen provoziert. Dabei geraten solche Fremde aus dem Blick, die als 'sonstige' oder 'insignifikante Andere' den modernen Alltag zu einem Großteil konstituieren bzw. durch wechselseitige Rituale der Distanznahme und Gleichgültigkeit zu solchen werden. Ausgehend von einer differenzierungstheoretischen Perspektive versucht der Artikel, neben den strukturellen Vor...

  18. En ny undersøgelse viser - eller gør den?

    DEFF Research Database (Denmark)

    Johansen, Kresten; Friis, Lars

    Danske medier præsenterer næsten dagligt resultater af undersøgelser, hvor et antal borgere er blevet spurgt om deres mening. Desværre er mange undersøgelser både dårligt gennemtænkt, halvhjertet udført og mangelfuldt analyseret. Det råder denne bog bod på. Uanset om du skal lave egne rundspørger...

  19. Charakterisierung der Verformungsmechanismen der stranggepressten Magnesiumlegierungen AZ31 und ME21 unter monotoner und zyklischer Belastung

    OpenAIRE

    Huppmann, Michael

    2011-01-01

    Magnesiumknetlegierungen sind attraktiv als Leichtbauwerkstoff für die Automobil- und die Luft- und Raumfahrtindustrie. Der Einsatz ist jedoch aufgrund der hexagonalen Kristallstruktur von Magnesiumlegierungen und der damit verbundenen eingeschränkten Umformeigenschaften bei Raumtemperatur, der Asymmetrie der mechanischen Eigenschaften und der Anisotropie hinsichtlich der plastischen Verformung eingeschränkt. Für eine wirtschaftliche Nutzung von Magnesiumlegierungen müssen die Eigenschaften d...

  20. Integration eines Anwendungssystems für die Tumordokumentation in ein klinisches Informationssystem

    OpenAIRE

    Stolte, Iris

    2001-01-01

    Die Tumordokumentation wurde bisher vor allem in Tumorzentren und klinischen Krebsregistern als retrospektive Erfassung der zu dokumentierenden Daten durchgeführt. Dieser Ansatz schränkt den Umfang der zu erhebenden Daten wegen des nicht unwesentlichen zusätzlichen Aufwands erheblich ein. Insbesondere für Aufgaben des Qualitätsmanagements, die in der Tumordokumentation immer stärker in den Vordergrund treten, ist es notwendig, umfangreiche, an Diagnose und Therapie der Patienten orie...

  1. The reasoning of architecture

    OpenAIRE

    Jacoby, Sam

    2013-01-01

    Diese Dissertation betrachtet Typus-Theorien als epistemologische und diskursive Argumente, durch die eine Synthese der Form der Architektur und der Stadt organisiert ist. Form erhält durch Typus-Begründungen eine vielschichtige historische, soziale, kulturelle und symbolische Dimension, die gleichzeitig beschränkt bei und mehr ist als ihrer stofflichen Wirklichkeit. Und es ist durch die Probleme des Typus und der Geschichtlichkeit, dass die moderne Begründung der Architektur definiert wurde....

  2. Age and CD161 Expression Contribute to Inter-Individual Variation in Interleukin-23 Response in CD8+ Memory Human T Cells

    OpenAIRE

    Hui Shen; Wei Zhang; Clara Abraham; Judy H Cho

    2013-01-01

    The interleukin-23 (IL-23) pathway plays a critical role in the pathogenesis of multiple chronic inflammatory disorders, however, inter-individual variability in IL-23-induced signal transduction in circulating human lymphocytes has not been well-defined. In this study, we observed marked, reproducible inter-individual differences in IL-23 responsiveness (measured by STAT3 phosphorylation) in peripheral blood CD8+CD45RO+ memory T and CD3+CD56+ NKT cells. Age, but not gender, was a significant...

  3. Stadtregionale Institutionalisierung und interkommunale Kooperation: Interkommunale Gewerbegebiete in der Region Stuttgart

    OpenAIRE

    Zwicker, Daniel

    1999-01-01

    Aufgrund kognitiver und prozessualer Kooperationshindernisse ist die Entstehung interkommunaler Gewerbegebiete zumeist auf räumliche oder fiskalische Zwangssituationen zwischen zwei Nachbargemeinden beschränkt. Damit interkommunale Gewerbegebiete zu einer nachhaltigeren Siedlungsentwicklung beitragen können, ist jedoch die Beteiligung mehrerer Gemeinden eines Teilraumes an einem optimalen Standort notwendig.Da diese Notwendigkeit besonders in Verdichtungsräumen gegeben ist, stellt sich die Fr...

  4. Untersuchung der Peroxisome-Proliferator-Activated-Receptor gamma-Polymorphismen 34C/G und 1431C/T auf eine Assoziation mit Restenose nach Stentimplantation in Koronararterien

    OpenAIRE

    Jung, Vanessa Viktoria

    2006-01-01

    Die koronare Herzkrankheit und ihre Folgen gelten bereits im mittleren Lebensalter als die Haupttodesursache in westlichen Industrieländern. Durchschlagenden Erfolg bei der Behandlung der koronaren Herzkrankheit hat die koronare Intervention mit Stentimplantation. Jedoch schränkt die Restenosierung der behandelten Koronargefäße den Langzeiterfolg immer noch bedeutend ein. Neben zahlreichen äußeren Einflussfaktoren während der Intervention spielen auch genetische Faktoren eine Rolle für die Au...

  5. Beiträge zur syntaktischen Analyse nicht-kontextfreier Sprachen

    OpenAIRE

    Bordihn, Henning

    2012-01-01

    Ansätze zum Parsing verschiedener Grammatikformalismen, die auch nicht-kontextfreie Sprachen erzeugen können, werden diskutiert. Chomsky-Grammatiken, Lindenmayer-Systeme, Grammatiken mit gesteuerten Ersetzungen und Grammatiksysteme werden behandelt. Formale Eigenschaften dieser Mechanismen als Akzeptoren von Sprachen werden untersucht. Weiterhin werden kooperierende verteilte (CD) Grammatiksysteme derart beschränkt, dass effizientes deterministisches Parsing ohne Backtracking möglich ist. Für...

  6. Susceptibility to Entamoeba histolytica intestinal infection is related to reduction in natural killer T-lymphocytes in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Fabrício M.S. Oliveira

    2012-04-01

    Full Text Available Entamoeba histolytica is a protozoan that causes amoebiasis. Recent studies demonstrated that natural killer T lymphocytes (NKT are critical for preventing the development of amoebic liver abscess. In spite of that, there are only a handful of studies in the area. Herein, we explored the role of NKT cells in E. histolytica infection using C57BL/6 wild-type and CD1-/- mice. Animals were inoculated with E. histolytica and sacrificed 48 hours later to collect caecum samples that were used for quantitative analyses of lesions, trophozoites, NK1.1+ T lymphocytes and expression of the mucus protein MUC-2 by immunohistochemistry technique. Quantitative analyses confirmed that the frequency of NK1.1+ T cells was significantly lower in samples from C57BL/6 CD1-/- mice as compared to their wild type (WT counterparts. The extension of necrotic mucosa was larger and the number of trophozoites higher in Entamoeba (Eh-infected CD1-/- mice when compared with Eh-infected WT mice. In mice from both groups, noninfected (CTRL and Eh-infected CD1-/-, there was a reduction in the thickness of the caecal mucosa and in the MUC-2-stained area in comparison with CTRL- and Eh-WT mice. Our results showed that NKT lymphocytes contribute to resistance against Entamoeba histolytica infection and to the control of inflammation in the colitis induced by infection. The presence of a normal epithelial layer containing appropriate levels of mucus had also a protective role against infection.

  7. Larger number of invariant natural killer T cells in PBSC allografts correlates with improved GVHD-free and progression-free survival.

    Science.gov (United States)

    Malard, Florent; Labopin, Myriam; Chevallier, Patrice; Guillaume, Thierry; Duquesne, Alix; Rialland, Fanny; Derenne, Sophie; Peterlin, Pierre; Leauté, Anne-Gaelle; Brissot, Eolia; Gregoire, Marc; Moreau, Philippe; Saas, Philippe; Gaugler, Béatrice; Mohty, Mohamad

    2016-04-01

    We studied the impact of a set of immune cells contained within granulocyte colony-stimulating factor-mobilized peripheral blood stem cell grafts (naïve and memory T-cell subsets, B cells, regulatory T cells, invariant natural killer T cells [iNKTs], NK cells, and dendritic cell subsets) in patients (n = 80) undergoing allogeneic stem cell transplantation (SCT), using the composite end point of graft-versus-host disease (GVHD)-free and progression-free survival (GPFS) as the primary end point. We observed that GPFS incidences in patients receiving iNKT doses above and below the median were 49% vs 22%, respectively (P= .007). In multivariate analysis, the iNKT dose was the only parameter with a significant impact on GPFS (hazard ratio = 0.48; 95% confidence interval, 0.27-0.85;P= .01). The incidences of severe grade III to IV acute GVHD and National Institutes of Health grade 2 to 3 chronic GVHD (12% and 16%, respectively) were low and associated with the use of antithymocyte globulin in 91% of patients. No difference in GVHD incidence was reported according to the iNKT dose. In conclusion, a higher dose of iNKTs within the graft is associated with an improved GPFS. These data may pave the way for prospective and active interventions aiming to manipulate the graft content to improve allo-SCT outcome.

  8. The Role of Innate Immune Cells in the Response of Heat-Treated Mycobacterium tuberculosis (M.tb) Antigens Stimulating PBMCs

    Institute of Scientific and Technical Information of China (English)

    Chao Wang; Jun Li; Huaixin Zheng; Haiming Wei; Ruijun Zhang; Baiqing Li; Zhigang Tian

    2004-01-01

    The proliferation response of γδT cells to the antigen from heat-treated Mycobacterium tuberculosis H37Ra (M.tb Ag) was used as a good model in γδT cell research. From preliminary research it is found that activated NK cells positively elevated γδT cells proliferation after simulating PBMCs with M. tb Ag. To investigate different behaviors of NK cells, γδNKT cells, γδT cells and relationships between these cell subsets, activation and proliferation of different cell subsets of PBMCs in response to M. tb Ag were analyzed. We demonstrated that NK cells, γδNKT cells and γδT cells could be activated after stimulation with M. tb Ag. γδNKT cells and γδT cells proliferated while the number of NK cells decreased after 11 day-simulation with M. tb Ag. Meanwhile, at the early time of stimulation the cytotoxicity of PBMCs was enhanced. Cellular & Molecular Immunology.2004;1(6):467-470.

  9. JUNB/AP-1 controls IFN-γ during inflammatory liver disease

    Science.gov (United States)

    Thomsen, Martin K.; Bakiri, Latifa; Hasenfuss, Sebastian C.; Hamacher, Rainer; Martinez, Lola; Wagner, Erwin F.

    2013-01-01

    Understanding the molecular pathogenesis of inflammatory liver disease is essential to design efficient therapeutic approaches. In hepatocytes, the dimeric transcription factor c-JUN/AP-1 is a major mediator of cell survival during hepatitis, although functions for other JUN proteins in liver disease are less defined. Here, we found that JUNB was specifically expressed in human and murine immune cells during acute liver injury. We analyzed the molecular function of JUNB in experimental models of hepatitis, including administration of concanavalin A (ConA) or α-galactosyl-ceramide, which induce liver inflammation and injury. Mice specifically lacking JUNB in hepatocytes displayed a mild increase in ConA-induced liver damage. However, targeted deletion of Junb in immune cells and hepatocytes protected against hepatitis in experimental models that involved NK/NKT cells. The absence of JUNB in immune cells decreased IFN-γ expression and secretion from NK and NKT cells, leading to reduced STAT1 pathway activation. Systemic IFN-γ treatment or adenovirus-based IRF1 delivery to Junb-deficient mice restored hepatotoxicity, and we demonstrate that Ifng is a direct transcriptional target of JUNB. These findings demonstrate that JUNB/AP-1 promotes cell death during acute hepatitis by regulating IFN-γ production in NK and NKT cells and thus functionally antagonizes the hepatoprotective function of c-JUN/AP-1 in hepatocytes. PMID:24200694

  10. TRPV1 Antagonism by Capsazepine Modulates Innate Immune Response in Mice Infected with Plasmodium berghei ANKA

    Directory of Open Access Journals (Sweden)

    Elizabeth S. Fernandes

    2014-01-01

    Full Text Available Thousands of people suffer from severe malaria every year. The innate immune response plays a determinant role in host’s defence to malaria. Transient receptor potential vanilloid 1 (TRPV1 modulates macrophage-mediated responses in sepsis, but its role in other pathogenic diseases has never been addressed. We investigated the effects of capsazepine, a TRPV1 antagonist, in malaria. C57BL/6 mice received 105 red blood cells infected with Plasmodium berghei ANKA intraperitoneally. Noninfected mice were used as controls. Capsazepine or vehicle was given intraperitoneally for 6 days. Mice were culled on day 7 after infection and blood and spleen cell phenotype and activation were evaluated. Capsazepine decreased circulating but not spleen F4/80+Ly6G+ cell numbers as well as activation of both F4/80+and F4/80+Ly6G+ cells in infected animals. In addition, capsazepine increased circulating but not spleen GR1+ and natural killer (NK population, without interfering with natural killer T (NKT cell numbers and blood NK and NKT activation. However, capsazepine diminished CD69 expression in spleen NKT but not NK cells. Infection increased lipid peroxidation and the release of TNFα and IFNγ, although capsazepine-treated group exhibited lower levels of lipid peroxidation and TNFα. Capsazepine treatment did not affect parasitaemia. Overall, TRPV1 antagonism modulates the innate immune response to malaria.

  11. Linking CD11b+ Dendritic Cells and Natural Killer T Cells to Plaque Inflammation in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Miche Rombouts

    2016-01-01

    Full Text Available Atherosclerosis remains the leading cause of death and disability in our Western society. To investigate whether the dynamics of leukocyte (subpopulations could be predictive for plaque inflammation during atherosclerosis, we analyzed innate and adaptive immune cell distributions in blood, plaques, and lymphoid tissue reservoirs in apolipoprotein E-deficient (ApoE−/− mice and in blood and plaques from patients undergoing endarterectomy. Firstly, there was predominance of the CD11b+ conventional dendritic cell (cDC subset in the plaque. Secondly, a strong inverse correlation was observed between CD11b+ cDC or natural killer T (NKT cells in blood and markers of inflammation in the plaque (including CD3, T-bet, CCR5, and CCR7. This indicates that circulating CD11b+ cDC and NKT cells show great potential to reflect the inflammatory status in the atherosclerotic plaque. Our results suggest that distinct changes in inflammatory cell dynamics may carry biomarker potential reflecting atherosclerotic lesion progression. This not only is crucial for a better understanding of the immunopathogenesis but also bares therapeutic potential, since immune cell-based therapies are emerging as a promising novel strategy in the battle against atherosclerosis and its associated comorbidities. The cDC-NKT cell interaction in atherosclerosis serves as a good candidate for future investigations.

  12. The Role of Innate Immune Cells in the Response of Heat-Treated Mycobacterium tuberculosis (M.tb) Antigens Stimulating PBMCs

    Institute of Scientific and Technical Information of China (English)

    ChaoWang; JunLi; HuaixinZheng; HaimingWei; RuijunZhang; BaiqingLi

    2004-01-01

    The proliferation response of γδT cells to the antigen from heat-treated Mycobacterium tuberculosis H37Ra (M.tb Ag) was used as a good model in γδT cell research. From preliminary research it is found that activated NK cells positively elevated γδT cells proliferation after simulating PBMCs with M.tb Ag. To investigate different behaviors of NK cells, γδNKT cells, γδT cells and relationships between these cell subsets, activation and proliferation of different cell subsets of PBMCs in response to M.tb Ag were analyzed. We demonstrated that NK cells, γδNKT cells and γδT cells could be activated after stimulation with M.tb Ag. γδNKT cells and γδT cells proliferated while the number of NK cells decreased after 11 day-simulation with M.tb Ag. Meanwhile, at the early time of stimulation the cytotoxicity of PBMCs was enhanced. Cellular & Molecular Immunology.2004;1(6):467-470.

  13. Effect of α-GalCer-activated natural killer T cell on survival of allograft with high-risk rejection after retrobubar injection%α-GalCer活化的自然杀伤T细胞对高危角膜移植后排斥反应的防治作用

    Institute of Scientific and Technical Information of China (English)

    宫妍; 宋丽艳; 孙海成

    2012-01-01

    背景 角膜移植排斥反应是导致角膜移植手术失败的主要原因,抑制角膜移植排斥反应的各种药物均有不良反应.研究发现自然杀伤T(NKT)细胞可致器官移植患者免疫耐受,但目前有关NKT细胞用于治疗高危角膜移植免疫反应的研究较少. 目的 探讨体外α-GalCer活化的NKT细胞在防治大鼠高危角膜移植免疫排斥反应中的作用. 方法 无菌条件下取Lewis大鼠脾脏淋巴细胞,加入质量浓度为100 mg/L的α-GalCer,在RPMI 1640培养基培养1周后,流式细胞仪分选出NKT细胞(密度为5×106个/ml).取10只Fisher 344大鼠为供体,20只Lewis大鼠为受体,受体角膜移植前1周角膜缝线诱导角膜新生血管(CNV).将受体大鼠按照随机数字表法随机分为NKT细胞组和生理盐水组,每组各10只.Lewis大鼠行穿透角膜移植.NKT细胞组在手术结束时球后注射0.1 ml NKT细胞液,生理盐水组注射相同体积的生理盐水.术后裂隙灯下观察记录角膜植片的反应情况并按照Holland的标准进行评分.术后第14天,两组各获取3只大鼠角膜植片行组织病理学检测,采用免疫组织化学法检测角膜植片中CD4+和CD8+T淋巴细胞的浸润情况.结果 生理盐水组角膜植片平均存活时间为(7.90±1.37)d,NKT细胞组为(14.70±1.49)d,差异有统计学意义(t=10.61,P=0.00).术后2周,生理盐水组角膜植片重度混浊水肿,大量炎性细胞浸润,新生血管长入植片,而NKT细胞组角膜植片仅轻度混浊、水肿,炎性细胞明显少于生理盐水组.免疫组织化学检测可见,生理盐水组角膜植片中大量CD4+和CD8+T淋巴细胞浸润,NKT细胞组中CD4+和CD8+T淋巴细胞明显减少.流式细胞仪检查结果表明,NKT细胞组大鼠脾脏中NKT细胞百分数为(5.67±0.25)%,明显高于生理盐水组的(1.21±0.19)%,差异有统计学意义(t=8.43,P=0.00).结论 α-GalCer活化的NKT细胞球后注射可以明显延长大鼠高危角膜移植植片的

  14. Clinical value of soluble triggering receptor expressed on myeloid cells-1 in the early diagnosis of patients with ventilator-associated pneumonia%呼出气冷凝液中可溶性髓系细胞触发受体-1检测对呼吸机相关性肺炎早期诊断的价值

    Institute of Scientific and Technical Information of China (English)

    周超; 沈美珠; 梁永杰; 李晓宁; 王秋波; 王岸; 魏丽; 薛菲

    2013-01-01

    目的 探讨呼吸机呼出气冷凝液(EVC)中可溶性髓系细胞触发受体-1(sTREM-1)对呼吸机相关性肺炎(VAP)早期诊断的临床意义.方法 以37例有创机械通气患者为研究对象,所有患者均在机械通气后第1 d、3 d、7 d应用双抗体夹心酶联免疫吸附法(DAS-ELISA)测定EVC中sTREM-1水平,根据治疗后评估,37例患者被分成非VAP组13例,VAP组24例(其中康复组14例,恶化组10例),应用受试者工作特征曲线(ROC)研究EVC sTREM-1对VAP早期诊断价值.结果第3 d,VAP组血清CRP、EVC sTREM-1均高于非VAP组(P0.05).应用ROC分析,以第3 d EVC sTREM-1 4.70 ng/ml为VAP的早期诊断界值,其敏感度为 95.8%,特异度为 92.3%.结论连续EVC中sTREM-1检测有助于VAP的早期诊断,而第7 d血清CRP和EVC中sTREM-1水平可能有助于判断VAP的预后(撤机失败和死亡)指标之一.

  15. 可溶性髓样细胞触发受体-1对脓毒血症早期诊断价值的研究%The early diagnostic value of soluble triggering receptor expressed on myeloid cell-1 in patients with sepsis

    Institute of Scientific and Technical Information of China (English)

    郭少卿; 邹原方

    2015-01-01

    目的:探讨血清可溶性髓样细胞触发受体‐1(sTREM‐1)对脓毒血症的早期诊断价值。方法选择2010年7月至2013年6月该院急诊重症病房重症监护病房收治的81例患者,其中61例全身炎症反应综合征(SIRS )患者,根据脓毒血症诊断标准分为脓毒血症组39例与SIRS组22例,非SIRS患者20例作为对照组,检测3组血清sTREM‐1和降钙素原(PCT)水平。结果脓毒血症组与SIRS组血清sTREM‐1及PCT水平均明显高于对照组(P<0.01);脓毒血症组血清sTREM‐1及PCT水平均明显高于SIRS组(P<0.01);sTREM‐1和PCT在SIRS患者中早期诊断脓毒血症的受试者工作特征曲线下面积分别为0.932和0.670,sTREM‐1的灵敏度和特异度分别为92.3%和86.4%,PCT 的灵敏度和特异度分别为61.5%和81.8%。结论血清sTREM‐1是脓毒血症早期诊断的较好指标,同时具有较高的灵敏度和特异度,优于PCT。%Objective To investigate the early diagnostic value of soluble triggering receptor expressed on myeloid cells‐1 (sTREM‐1) in patients with sepsis .Methods Eighty‐one patients between July 2010 and June 2013 were collected .Sixty one pa‐tients with systemic inflammatory response syndrome (SIRS) were divided into sepsis group (n=39) and SIRS group (n=22) ,and the other 20 patients without SIRS were as control group .Levels of sTREM‐1 and procalcitonin (PCT ) were measured .Results The levels of sTREM‐1 and PCT were significant higher in sepsis group and SIRS group than those in control group (P<0 .01) , and the levels of sTREM‐1 and PCT in sepsis group were significant higher than those in SIRS group (P<0 .01) .The area under the curve (AUC) of sTREM‐1 and PCT were 0 .932 and 0 .670 ,respectively .The sensibility and specificity of sTREM‐1 were 92 .3% and 86 .4% ,while the sensibility and specificity of PCT were 61 .5% and 81 .8% .Conclusion Serum sTREM‐1 might be a good biomarker for the early diagnosis of sepsis ,and it has higher sensitivity and specificity in compassion with PCT .

  16. Effects of 1, 25 ( OH ) 2D3 on parathyroid hormone induced transdifferentiation and TGF-β1 expression in cultured human renal tubular epithelial cells%1,25(OH)2D3对甲状旁腺素诱导的肾小管上皮细胞转分化和TGF-β1的表达的影响

    Institute of Scientific and Technical Information of China (English)

    李晓东; 李英; 丁新国; 高山林; 郭志军

    2012-01-01

    AIM: To explore the effects of 1, 25 (OH)2D3 on parathyroid hormone (PTH) induced transdif-ferentiation and TGF-p, expression in cultured human renal tubular epithelial cells. METHODS: HK-2 cells were cultured in DMEM/F12 medium supplemented with 50 mL/L FBS. Cells were divided into three groups. (1) Control group: without PTH or 1, 25(OH)2D3; (2) PTH group: 10-10mol/LPTH; (3) PTH and 1, 25(OH)2D3 group: 10-10 mol/L PTH and different concentrations of 1, 25(OH)2D3 (10-10, 10-9, 10-8 and 10-7 mol/L). The gene expressions of a-SMA and TGF-p, were detected by semi-quantitative RT-PCR. The protein expressions of a-SMA and TGF-p, were detected by Western blot. Immunocytochemisty (ICC) was used to measure the expression of a-SMA in HK-2. ELISA was used to assay the level of TGF-p, in the supernatant. RESULTS: The gene expressions of a-SMA and TGF-p, in PTH group were significantly higher than those in control group (P<0.05). In contrast, they were significantly lower in PTH and 1, 25(OH)2D3 group than those in PTH group ( P < 0. 05). Western blot results showed α-SMA could not be detected in normal HK-2 cells, which could be detected in PTH group. TGF-p, protein expression in PTH group was higher than that in control group. In PTH and 1, 25(OH)2D3 group, a-SMA and TGF-p, protein expressions were significantly lower than those in PTH group ( P <0.05). ICC results showed that a-SMA was hardly expressed in cells of control group. However, positive expression of a-SMA could be seen in many cells in PTH group. In PTH and 1, 25(OH)2D3 group, the cells of a-SMA positive expressed were significantly less than those in PTH group (P<0.05). ELISA results showed that the level of TGF-p, in the supernatant of PTH group was higher than that in control group, which was also higher than that in PTH and 1, 25 (OH)2D3 group (P<0. 05). CONCLUSION; 1, 25(OH)2D3 can attenuate PTH-induced transdifferentiation and TGF-p, expression in cultured human renal tubular epithelial cells.%目的:探讨1,25(OH)2D3对甲状旁腺素(PTH)诱导的肾小管上皮细胞转分化和转化生长因子-β1(TGF-β1)表达的影响.方法:人肾小管上皮细胞(HK-2细胞)培养在含50 mL/L FCS的DMEM/F12培养液中.对照组:加入等体积含50 mL/L FCS的DMEM/F12培养液;PTH刺激组:加入终浓度为10-10 mol/L PTH的含50 mL/L FCS的DMEM/F12培养液;PTH +1,25(OH)2D3干预组:加入10-10 mol/L PTH,同时加入不同浓度( 10-10、10-9、10-8、10-7 mol/L)的1,25(OH)2D3.刺激HK-2细胞48 h.半定量RT-PCR法检测细胞中α-平滑肌肌动蛋白(α-SMA)和TGF-β1的基因表达;Western blot法检测细胞中α-SMA和TGF-β1的蛋白表达;免疫细胞化学法检测细胞中α-SMA的表达;ELISA法检测细胞培养上清液中TGF-β1的含量.结果:半定量RT-PCR结果显示,对照组HK-2细胞中几乎无α-SMA的mRNA表达,仅有少量的TGF-β1mRNA表达;PTH刺激组α-SMA和TGF-β1mRNA表达量与对照组比较明显增加;PTH +1,25 (OH)2D3干预组表达量比PTH刺激组显著降低,且随着1,25(OH)2D3浓度的升高呈一定的剂量依赖性(P<0.05).Westem blot结果显示,对照组HK-2细胞中无α-SMA的蛋白表达,仅有少量的TGF-β1蛋白表达;10-10 mol/L的PTH能够明显诱导HK-2细胞中α-SMA的蛋白表达,增加TGF-β1的蛋白表达量;PTH+1,25(OH)2D3干预组,α-SMA和TGF-β1的蛋白表达量比PTH刺激组显著降低(P<0.05).免疫细胞化学法结果显示,对照组几乎无α-SMA阳性表达的细胞,PTH刺激组可见大量细胞α-SMA表达阳性;PTH +1,25(OH)2D3干预组α-SMA表达阳性的细胞数明显低于PTH刺激组(P<0.05).ELISA结果显示,对照组细胞上清液中可检测到少量的TGF-β1,PTH刺激组含量显著升高,PTH +1,25(OH)2D3干预组与PTH刺激组比较含量明显降低(P<0.05).结论:1,25(OH)2D3能够部分拮抗PTH诱导的HK-2细胞转分化和TGF-β1的表达.

  17. Restricting nonclassical MHC genes coevolve with TRAV genes used by innate-like T cells in mammals.

    Science.gov (United States)

    Boudinot, Pierre; Mondot, Stanislas; Jouneau, Luc; Teyton, Luc; Lefranc, Marie-Paule; Lantz, Olivier

    2016-05-24

    Whereas major histocompatibility class-1 (MH1) proteins present peptides to T cells displaying a large T-cell receptor (TR) repertoire, MH1Like proteins, such as CD1D and MR1, present glycolipids and microbial riboflavin precursor derivatives, respectively, to T cells expressing invariant TR-α (iTRA) chains. The groove of such MH1Like, as well as iTRA chains used by mucosal-associated invariant T (MAIT) and natural killer T (NKT) cells, respectively, may result from a coevolution under particular selection pressures. Herein, we investigated the evolutionary patterns of the iTRA of MAIT and NKT cells and restricting MH1Like proteins: MR1 appeared 170 Mya and is highly conserved across mammals, evolving more slowly than other MH1Like. It has been pseudogenized or independently lost three times in carnivores, the armadillo, and lagomorphs. The corresponding TRAV1 gene also evolved slowly and harbors highly conserved complementarity determining regions 1 and 2. TRAV1 is absent exclusively from species in which MR1 is lacking, suggesting that its loss released the purifying selection on MR1. In the rabbit, which has very few NKT and no MAIT cells, a previously unrecognized iTRA was identified by sequencing leukocyte RNA. This iTRA uses TRAV41, which is highly conserved across several groups of mammals. A rabbit MH1Like gene was found that appeared with mammals and is highly conserved. It was independently lost in a few groups in which MR1 is present, like primates and Muridae, illustrating compensatory emergences of new MH1Like/Invariant T-cell combinations during evolution. Deciphering their role is warranted to search similar effector functions in humans. PMID:27170188

  18. Protective mucosal immunity mediated by epithelial CD1d and IL-10.

    Science.gov (United States)

    Olszak, Torsten; Neves, Joana F; Dowds, C Marie; Baker, Kristi; Glickman, Jonathan; Davidson, Nicholas O; Lin, Chyuan-Sheng; Jobin, Christian; Brand, Stephan; Sotlar, Karl; Wada, Koichiro; Katayama, Kazufumi; Nakajima, Atsushi; Mizuguchi, Hiroyuki; Kawasaki, Kunito; Nagata, Kazuhiro; Müller, Werner; Snapper, Scott B; Schreiber, Stefan; Kaser, Arthur; Zeissig, Sebastian; Blumberg, Richard S

    2014-05-22

    The mechanisms by which mucosal homeostasis is maintained are of central importance to inflammatory bowel disease. Critical to these processes is the intestinal epithelial cell (IEC), which regulates immune responses at the interface between the commensal microbiota and the host. CD1d presents self and microbial lipid antigens to natural killer T (NKT) cells, which are involved in the pathogenesis of colitis in animal models and human inflammatory bowel disease. As CD1d crosslinking on model IECs results in the production of the important regulatory cytokine interleukin (IL)-10 (ref. 9), decreased epithelial CD1d expression--as observed in inflammatory bowel disease--may contribute substantially to intestinal inflammation. Here we show in mice that whereas bone-marrow-derived CD1d signals contribute to NKT-cell-mediated intestinal inflammation, engagement of epithelial CD1d elicits protective effects through the activation of STAT3 and STAT3-dependent transcription of IL-10, heat shock protein 110 (HSP110; also known as HSP105), and CD1d itself. All of these epithelial elements are critically involved in controlling CD1d-mediated intestinal inflammation. This is demonstrated by severe NKT-cell-mediated colitis upon IEC-specific deletion of IL-10, CD1d, and its critical regulator microsomal triglyceride transfer protein (MTP), as well as deletion of HSP110 in the radioresistant compartment. Our studies thus uncover a novel pathway of IEC-dependent regulation of mucosal homeostasis and highlight a critical role of IL-10 in the intestinal epithelium, with broad implications for diseases such as inflammatory bowel disease. PMID:24717441

  19. IL-22-producing RORγt-dependent innate lymphoid cells play a novel protective role in murine acute hepatitis.

    Directory of Open Access Journals (Sweden)

    Atsuhiro Matsumoto

    Full Text Available Retinoid-related orphan receptor (ROR γt is known to be related to the development and function of various immunological compartments in the liver, such as Th17 cells, natural killer T (NKT cells, and innate lymphoid cells (ILCs. We evaluated the roles of RORγt-expressing cells in mouse acute hepatitis model using RORγt deficient (RORγt(-/- mice and RAG-2 and RORγt double deficient (RAG-2(-/- × RORγt(-/- mice. Acute hepatitis was induced in mice by injection with carbon tetrachloride (CCl4, to investigate the regulation of liver inflammation by RORγt-expressing cells. We detected RORC expression in three compartments, CD4(+ T cells, NKT cells, and lineage marker-negative SCA-1(+Thy1(high ILCs, of the liver of wild type (WT mice. CCl4-treated RORγt(-/- mice developed liver damage in spite of lack of RORγt-dependent cells, but with reduced infiltration of macrophages compared with WT mice. In this regard, ILCs were significantly decreased in RAG-2(-/- × RORγt(-/- mice that lacked T and NKT cells. Surprisingly, RAG-2(-/- × RORγt(-/- mice developed significantly severer CCl4-induced hepatitis compared with RAG-2(-/- mice, in accordance with the fact that hepatic ILCs failed to produce IL-22. Lastly, anti-Thy1 monoclonal antibody (mAb, but not anti-NK1.1 mAb or anti-asialo GM1 Ab administration exacerbated liver damage in RAG-2(-/- mice with the depletion of liver ILCs. Collectively, hepatic RORγt-dependent ILCs play a part of protective roles in hepatic immune response in mice.

  20. The Nitric Oxide Synthase Inhibitor NG-Nitro-L-Arginine Methyl Ester Diminishes the Immunomodulatory Effects of Parental Arginine in Rats with Subacute Peritonitis.

    Science.gov (United States)

    Lo, Hui-Chen; Hung, Ching-Yi; Huang, Fu-Huan; Su, Tzu-Cheng; Lee, Chien-Hsing

    2016-01-01

    The combined treatment of parenteral arginine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) have been shown to improve liver function and systemic inflammation in subacute peritonitic rats. Here, we investigated the effects of single and combined parenteral arginine and L-NAME treatments on leukocyte and splenocyte immunity. Male Wistar rats were subjected to cecal punctures and were intravenously given total parenteral nutrition solutions with or without arginine and/or L-NAME supplementations for 7 days. Non-surgical and sham-operated rats with no cecal puncture were given a chow diet and parenteral nutrition, respectively. Parenteral feeding elevated the white blood cell numbers and subacute peritonitis augmented the parenteral nutrition-induced alterations in the loss of body weight gain, splenomegaly, and splenocyte decreases. Parenteral arginine significantly increased the B-leukocyte level, decreased the natural killer T (NKT)-leukocyte and splenocyte levels, alleviated the loss in body weight gain and total and cytotoxic T-splenocyte levels, and attenuated the increases in plasma nitrate/nitrite and interferon-gamma production by T-splenocytes. L-NAME infusion significantly decreased NKT-leukocyte level, tumor-necrosis factor (TNF)-alpha production by T-splenocytes and macrophages, and interferon-gamma production by T-leukocytes, monocytes, and T-splenocytes, as well as increased interleukin-6 production by T-leukocytes and monocytes and nitrate/nitrite production by T-leukocytes. Combined treatment significantly decreased plasma nitrate/nitrite, the NKT-leukocyte level, and TNF-alpha production by T-splenocytes. Parenteral arginine may attenuate immune impairment and L-NAME infusion may augment leukocyte proinflammatory response, eliminate splenocyte proinflammatory and T-helper 1 responses, and diminish arginine-induced immunomodulation in combined treatment in subacute peritonitic rats.

  1. Kelvin Absolute Temperature Scale Identified as Length Scale and Related to de Broglie Thermal Wavelength

    Science.gov (United States)

    Sohrab, Siavash

    Thermodynamic equilibrium between matter and radiation leads to de Broglie wavelength λdβ = h /mβvrβ and frequency νdβ = k /mβvrβ of matter waves and stochastic definitions of Planck h =hk =mk c and Boltzmann k =kk =mk c constants, λrkνrk = c , that respectively relate to spatial (λ) and temporal (ν) aspects of vacuum fluctuations. Photon massmk =√{ hk /c3 } , amu =√{ hkc } = 1 /No , and universal gas constant Ro =No k =√{ k / hc } result in internal Uk = Nhνrk = Nmkc2 = 3 Nmkvmpk2 = 3 NkT and potential pV = uN\\vcirc / 3 = N\\ucirc / 3 = NkT energy of photon gas in Casimir vacuum such that H = TS = 4 NkT . Therefore, Kelvin absolute thermodynamic temperature scale [degree K] is identified as length scale [meter] and related to most probable wavelength and de Broglie thermal wavelength as Tβ =λmpβ =λdβ / 3 . Parallel to Wien displacement law obtained from Planck distribution, the displacement law λwS T =c2 /√{ 3} is obtained from Maxwell -Boltzmann distribution of speed of ``photon clusters''. The propagation speeds of sound waves in ideal gas versus light waves in photon gas are described in terms of vrβ in harmony with perceptions of Huygens. Newton formula for speed of long waves in canals √{ p / ρ } is modified to √{ gh } =√{ γp / ρ } in accordance with adiabatic theory of Laplace.

  2. Team anderthalb : Hochspannung

    OpenAIRE

    Meier, Karlheinz

    2000-01-01

    Die Fakultät für Physik und Astronomie produziert in regelmäßiger Folge für das Universitätsmagazin CAMPUS TV Filme über physikalische Phänomene. Die Länge der Filme ist auf jeweils 90 Sekunden (oder anderthalb Minuten) beschränkt, woraus sich der Titel der Serie 'Team anderthalb' ergibt. In dieser Folge wird die „Hochspannung“ behandelt. Ein Wasserschlauch macht deutlich, was es mit Strom, Spannung und Widerstand aus der Elektrizitätslehre auf sich hat. Nikola Tesla hat wichtige Erfindungen...

  3. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury

    Energy Technology Data Exchange (ETDEWEB)

    Fullerton, Aaron M., E-mail: fuller22@msu.edu [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, 1129 Farm Lane, Room 215, East Lansing, MI 48824 (United States); Roth, Robert A., E-mail: rothr@msu.edu [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, Food Safety and Toxicology Building, 1129 Farm Lane, Room 221, East Lansing, MI 48824 (United States); Ganey, Patricia E., E-mail: ganey@msu.edu [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, Food Safety and Toxicology Building, 1129 Farm Lane, Room 214, East Lansing, MI 48824 (United States)

    2013-01-15

    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30 μg/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD pretreatment increased liver injury resulting from moderate doses of Con A (4–10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFNγ), and TCDD/Con A-induced hepatotoxicity was attenuated in IFNγ knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cell–cell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression. -- Highlights: ► TCDD pretreatment sensitizes mice to Con A-induced hepatotoxicity. ► TCDD pretreatment increased concentration of IFNγ in plasma after Con A. ► Con A-induced activation of NKT cells was increased by TCDD pretreatment. ► Fas

  4. The NKG2D Ligands RAE-1δ and RAE-1ε Differ with Respect to Their Receptor Affinity, Expression Profiles and Transcriptional Regulation

    OpenAIRE

    Cédile, Oriane; Popa, Natalia; Pollet-Villard, Frédéric; Garmy, Nicolas; Ibrahim, El Chérif; Boucraut, José

    2010-01-01

    Background RAE-1 is a ligand of the activating receptor NKG2D expressed by NK cells, NKT, γδT and some CD8+T lymphocytes. RAE-1 is overexpressed in tumor cell lines and its expression is induced after viral infection and genotoxic stress. We have recently demonstrated that RAE-1 is expressed in the adult subventricular zone (SVZ) from C57BL/6 mice. RAE-1 is also expressed in vitro by neural stem/progenitor cells (NSPCs) and plays a non-immune role in cell proliferation. The C57BL/6 mouse geno...

  5. Genotypische Variation der Überdauerungsneigung von transgenem und konventionell gezüchtetem Raps und Möglichkeiten der Beeinflussung durch Bodenbearbeitung als Beitrag zur Sicherheitsforschung bei transgenen Kulturpflanzen

    OpenAIRE

    Gruber, Sabine

    2004-01-01

    Hohe Ausfallverluste bei der Rapsernte und die Ausbildung sekundärer Dormanz in den Samen können zum Aufbau eines langjährigen Bodensamenvorrats führen. Aus diesem Samenvorrat auflaufender Durchwuchsraps ist in Folgekulturen oft nur eingeschränkt chemisch oder mechanisch zu kontrollieren, besonders in einem späteren, erneuten Rapsbestand. Neben pflanzenbaulichen Nachteilen gewinnt die Thematik beim Anbau gentechnisch veränderter Rapssorten wegen der Möglichkeit unerwünschten Gentransfers über...

  6. Team anderthalb : Magnetbremse

    OpenAIRE

    Meier, Karlheinz

    2000-01-01

    Die Fakultät für Physik und Astronomie produziert in regelmäßiger Folge für das Universitätsmagazin CAMPUS TV Filme über physikalische Phänomene. Die Länge der Filme ist auf jeweils 90 Sekunden (oder anderthalb Minuten) beschränkt, woraus sich der Titel der Serie 'Team anderthalb' ergibt. In dieser Folge wird die „Magnetbremse“ behandelt. Magnete lassen sich durch ihren Aufbau aus sehr vielen Elementarmagneten erklären. Wie stark die Kraft dieser sehr kleinen Magnete werden kann, zeigen Magn...

  7. Supercontinuum - broad as a lamp, bright as a laser, now in the mid-infrared

    DEFF Research Database (Denmark)

    Moselund, Peter M.; Petersen, Christian; Dupont, Sune;

    2012-01-01

    Based on the experience gained developing our market leading visible spectrum supercontinuum sources NKT Photonics has built the first mid-infrared supercontinuum source based on modelocked picosecond fiber lasers. The source is pumped by a ≈ 2 um laser based on a combination of erbium and thulium...... and use ZBLAN fibers to generate a 1.75-4.4 μm spectrum. We will present results obtained by applying the source for mid-infrared microscopy where absorption spectra can be used to identify the chemical nature of different parts of a sample. Subsequently, we discuss the possible application of a mid...

  8. Integrating Unlocking of Organizational Paths into an Agent-Based Simulation Model

    OpenAIRE

    Obschonka, Felix

    2014-01-01

    Das Berliner Drei-Phasen-Modell pfadabhängiger Prozesse erklärt, wie die Handlungsfähigkeit von Organisationen aufgrund selbstverstärkender Effekte eingeschränkt werden kann. Das Phänomen Pfadbruch, bei welchem Organisationen etablierte Pfade verlassen, wird darin nur unzureichend beschrieben. Obwohl in der Managementliteratur verschiedene Möglichkeiten zum Aufbrechen von Pfadabhängigkeiten diskutiert werden, fehlt eine systematische Überprüfung, ob und wie organisationale Pfade geb...

  9. Flüchtlinge und Schule? Erfahrungen

    OpenAIRE

    Kauffmann, Heiko; Knapp, Anny; Novotny, Eva; Schoch, Sabine

    2002-01-01

    [Die Autoren beleuchten die Situation staatlich noch nicht anerkannter], junger Flüchtlinge in der Bundesrepublik Deutschland, in Österreich und in der Schweiz. Heiko Kaufmann stellt die Frage des Zugangs zu Bildungsstrukturen in den Kontext der UN- Kinderrechtskonvention und der sogenannten "Vorbehaltserklärung" der Bundesrepublik Deutschland. Durch diese wird die Reichweite der Konvention mit dem Verweis auf die Priorität des deutschen Ausländerrechts erheblich beschränkt. Die ungenügende A...

  10. Erfassung und Modellierung der Schneeschmelzerosion am Beispiel der Kleineinzugsgebiete Schäfertal (Deutschland) und Lubazhinkha (Russland)

    OpenAIRE

    Ollesch, Gregor

    2010-01-01

    Bodenerosion durch Wasser ist ein ubiquitäres Problem, dass sowohl die landwirtschaftliche Produktivität vermindert, Bodenfunktionen einschränkt und auch in anderen Umweltkompartimenten schädliche Auswirkungen haben kann. Oberflächengewässer sind durch die mit Bodenerosion einhergehende Belastung durch Sediment, sedimentgebundenen und gelösten Nährstoffen sowie anderen Schadstoffen besonders betroffen. Das Wissen über Erosionsprozesse und Sedimentfrachten hat daher große Bedeutung für den Sch...

  11. Archimedean Quadratic Modules : A Decision Problem for Real Multivariate Polynomials

    OpenAIRE

    Wagner, Sven

    2009-01-01

    Wir zeigen die Entscheidbarkeit der Archimedizität eines endlich erzeugten quadratischen Moduls im Ring aller reellen Polynome in mehreren gegebenen Veränderlichen. Letzteres ist äquivalent zu der Frage, ob die von endlich vielen gegebenen reellen Polynomen erzeugte abgeschlossene semialgebraische Menge beschränkt ist, und ob jedes auf dieser Menge strikt positive reelle Polynom eine Darstellung als Summe von Quadraten, die mit den gegebenen Polynomen gewichtet sein können, besitzt. Dafür ver...

  12. Assessment of Some Immune Parameters in Occupationally Exposed Nuclear Power Plants Workers

    OpenAIRE

    Gyuleva, Ilona; Panova, Delyana; Djounova, Jana; Rupova, Ivanka; Penkova, Kalina

    2015-01-01

    The purpose of this article is to analyze the results of a 10-year survey of the radiation effects of some immune parameters of occupationally exposed personnel from the Nuclear Power Plant “Kozloduy”, Bulgaria. 438 persons working in NPP with cumulative doses between 0.06 mSv and 766.36mSv and a control group with 65 persons were studied. Flow cytometry measurements of T, B, natural killer (NK) and natural killer T (NKT) cell lymphocyte populations were performed. Data were interpreted with ...

  13. Clinicopathological analysis of cutaneous natural killer/T cell lymphoma: 36 case report%36例皮肤天然杀伤细胞/T细胞淋巴瘤临床病理学研究

    Institute of Scientific and Technical Information of China (English)

    徐教生; 谷从友; 安方; 高子芬; 李敏; 黄欣; 张永红; 周春菊; 薛学敏; 段泽君; 孙琳; 刘翠苓

    2011-01-01

    目的 探讨皮肤天然杀伤细胞(NK)/T细胞淋巴瘤临床病理学特点、与EB病毒的关系及预后。方法 收集2000—2010年北京大学医学部病理学系确诊为皮肤NK/T细胞淋巴瘤36例,分为原发与继发两组,分别观察临床病理学特点及与EB病毒的关系,并进行随访。结果 36例皮肤NK/T细胞淋巴瘤中,原发13例,继发20例,未能明确原发或继发3例。原发性与继发性皮肤NK/T细胞淋巴瘤均以男性好发,但两组男女性别比差异无统计学意义(P>0.05)。与原发者相比,继发者发病年龄早(中位年龄,43.5比54岁,P< 0.05)、且临床上出现B症状(包括发热、盗汗或体质量下降)及多发皮损改变的频率较高(P值分别为<0.05和<0.01)。EB病毒在原发和继发病例中的检出率类似,分别为92.3%和85%。36例皮肤NK/T细胞淋巴瘤中位生存期为8个月,其中继发性皮肤NK/T细胞淋巴瘤中位生存期为6个月,明显短于原发者(18个月,x2= 6.074,P<0.05)。结论 皮肤NK/T细胞淋巴瘤是一组与EB病毒密切相关、临床侵袭性强的肿瘤。但原发者较继发者发病年龄晚、预后较好。%Objective To investigate the clinicopathological features and prognosis of natural killer (NK)/T cell lymphoma and to analyze its relationship with Epstein-barr virus (EBV). Methods Totally, 36 cases of cutaneous NK/T cell lymphoma were collected from 2000 to 2010 at the Department of Pathology, Peking University Health Science Center, and classified into primary and secondary groups according to whether there is evidence of extracutaneous involvement within 6 months after diagnosis. Clinicopathological features were analyzed and Epstein-barr virus (EBV) was detected. Results Of these 36 cases, 13 (36.1%) were classified as primary cutaneous NK/T cell lymphoma, 20 (55.6%) as secondary, and 3 (8.3%) remained unclassified because of the lack of clinical data. Males were more likely

  14. Renaturierung von Fließgewässern

    Science.gov (United States)

    Lüderitz, Volker; Jüpner, Robert

    Beim Umgang mit den Gewässern wurde der wasserbaulichen Durchsetzung bestimmter Nutzungsansprüche, vor allem der Landwirtschaft, dem Hochwasserschutz, der Wassergewinnung, der Schifffahrt und der Energiegewinnung über Jahrhunderte absoluter Vorrang vor den Belangen des ökologischen Zustandes der Gewässer selbst und damit auch ihrer multifunktionalen Nutzbarkeit eingeräumt. Die daraus resultierenden Umweltauswirkungen wurden oft billigend in Kauf genommen. Gezielte Verbesserungen der ökologischen Situation von Gewässern bzw. Gewässerabschnitten, wie z.B. der Einsatz ingenieurbiologischer Bauweisen oder der Einbau von Fischwanderhilfen an Mühlenstauen, blieben auf Ausnahmen beschränkt.

  15. Allmänläkares och socialarbetares respons på riskreduceringsteknologier : en litteraturstudie

    OpenAIRE

    Rexvid, Devin; Blom, Björn; Evertsson, Lars; Forssén, Annika

    2012-01-01

    Bakgrund: Allmänläkare och socialarbetare utgör exempel på välfärdsprofessioner vars villkor anses ha förändrats i det så kallade risk- och granskningssamhället. Minskad autonomi, inskränkt diskretion och försvagad jurisdiktion lyfts i professionsforskningen fram som några av uttrycksformerna för de förändrade villkoren.   Syfte: Att beskriva och analysera allmänläkares och socialarbetares respons på evidensbaserade och organisatoriska riskreduceringsteknologier (ERRT och ORRT). Metod: Artik...

  16. Prädiktiver Wert sensorischer Laboruntersuchungen für den Getränkekonsum älterer Menschen unter Alltagsbedingungen

    OpenAIRE

    Hoyer, Stephan W.

    2005-01-01

    Zur Ermittlung der Akzeptanz und ihres prädiktiven Wertes für den Verzehr von Lebensmitteln bzw. Getränken, sind Beliebtheitsprüfungen mit Konsumenten unter standardisierten Bedingungen im Sensoriklabor üblich. Die prädiktive Aussagekraft dieser Laboruntersuchungen wird jedoch durch folgende Aspekte eingeschränkt: (1) Der situative Kontext wird ausgeschaltet, d.h. die Verzehrssituation, in der ein Produkt üblicherweise konsumiert wird, ist im Labor bewusst eliminiert und das zu bewertende Pr...

  17. Struktur und Korrosionsverhalten nichtrostender Stähle nach einer chemisch-thermischen Behandlung bei tiefen Temperaturen

    OpenAIRE

    Münter, Daniel

    2010-01-01

    Rost- und säurebeständige Stähle, wie z.B. der Austenit 1.4404, zeichnen sich durch eine hervorragende Korrosionsbeständigkeit aus. Der Einsatz dieser Stähle war aber aufgrund ihrer schlechten Verschleißeigenschaften bisher eher eingeschränkt. Um diesen Anforderungen gerecht zu werden, ist es notwendig, eine Oberflächenmodifizierung vorzunehmen. Dies kann besonders mit Nitrier- und Carburierverfahren bzw. einer Kombination aus beiden erreicht werden, wobei das im Mischkristall gelöste Chrom n...

  18. Sklerosierung von Ösophagus- und Magenvarizen : Eine repräsentative Retrospektivstudie ; Ergebnisse und methodischer Ausblick

    OpenAIRE

    Nolte, Claus

    2010-01-01

    Magenvarizen Bei 19 (11,6%) der 164 Patienten mit ÖV wurden zusätzlich MV diagnostiziert. Bei 15 von ihnen handelte es sich um junktionale Varizen des Lokalisationstypus GOV1 und GOV2. Die übrigen vier Patienten wiesen MV vom Typ IGV1 auf, davon drei, bei denen die Varizen nicht auf ein umschriebenes Fundusareal beschränkt waren, sondern unterschiedlich große Korpusbereiche mit einschlossen. Bei 11 der 15 Patienten mit junktionalen Varizen bildeten sich diese in typischer Weise...

  19. Recipient myeloid-derived immunomodulatory cells induce PD-1 ligand-dependent donor CD4+Foxp3+ regulatory T cell proliferation and donor-recipient immune tolerance after murine nonmyeloablative bone marrow transplantation.

    Science.gov (United States)

    van der Merwe, Marie; Abdelsamed, Hossam A; Seth, Aman; Ong, Taren; Vogel, Peter; Pillai, Asha B

    2013-12-01

    We showed previously that nonmyeloablative total lymphoid irradiation/rabbit anti-thymocyte serum (TLI/ATS) conditioning facilitates potent donor-recipient immune tolerance following bone marrow transplantation (BMT) across MHC barriers via recipient invariant NKT (iNKT) cell-derived IL-4-dependent expansion of donor Foxp3(+) naturally occurring regulatory T cells (nTregs). In this study, we report a more specific mechanism. Wild-type (WT) BALB/c (H-2(d)) hosts were administered TLI/ATS and BMT from WT or STAT6(-/-) C57BL/6 (H-2(b)) donors. Following STAT6(-/-) BMT, donor nTregs demonstrated no loss of proliferation in vivo, indicating that an IL-4-responsive population in the recipient, rather than the donor, drives donor nTreg proliferation. In graft-versus-host disease (GVHD) target organs, three recipient CD11b(+) cell subsets (Gr-1(high)CD11c(-), Gr-1(int)CD11c(-), and Gr-1(low)CD11c(+)) were enriched early after TLI/ATS + BMT versus total body irradiation/ATS + BMT. Gr-1(low)CD11c(+) cells induced potent H-2K(b+)CD4(+)Foxp3(+) nTreg proliferation in vitro in 72-h MLRs. Gr-1(low)CD11c(+) cells were reduced significantly in STAT6(-/-) and iNKT cell-deficient Jα18(-/-) BALB/c recipients after TLI/ATS + BMT. Depletion of CD11b(+) cells resulted in severe acute GVHD, and adoptive transfer of WT Gr-1(low)CD11c(+) cells to Jα18(-/-) BALB/c recipients of TLI/ATS + BMT restored day-6 donor Foxp3(+) nTreg proliferation and protection from CD8 effector T cell-mediated GVHD. Blockade of programmed death ligand 1 and 2, but not CD40, TGF-β signaling, arginase 1, or iNOS, inhibited nTreg proliferation in cocultures of recipient-derived Gr-1(low)CD11c(+) cells with donor nTregs. Through iNKT-dependent Th2 polarization, myeloid-derived immunomodulatory dendritic cells are expanded after nonmyeloablative TLI/ATS conditioning and allogeneic BMT, induce PD-1 ligand-dependent donor nTreg proliferation, and maintain potent graft-versus-host immune tolerance.

  20. Interaktiv 3D design

    DEFF Research Database (Denmark)

    Villaume, René Domine; Ørstrup, Finn Rude

    2002-01-01

    Projektet undersøger potentialet for interaktiv 3D design via Internettet. Arkitekt Jørn Utzons projekt til Espansiva blev udviklet som et byggesystem med det mål, at kunne skabe mangfoldige planmuligheder og mangfoldige facade- og rumudformninger. Systemets bygningskomponenter er digitaliseret som...... 3D elementer og gjort tilgængelige. Via Internettet er det nu muligt at sammenstille og afprøve en uendelig  række bygningstyper som  systemet blev tænkt og udviklet til....

  1. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury

    International Nuclear Information System (INIS)

    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30 μg/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD pretreatment increased liver injury resulting from moderate doses of Con A (4–10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFNγ), and TCDD/Con A-induced hepatotoxicity was attenuated in IFNγ knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cell–cell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression. -- Highlights: ► TCDD pretreatment sensitizes mice to Con A-induced hepatotoxicity. ► TCDD pretreatment increased concentration of IFNγ in plasma after Con A. ► Con A-induced activation of NKT cells was increased by TCDD pretreatment. ► Fas

  2. Utveckling av hotspotsystem

    OpenAIRE

    Baktirovic, Adnan

    2008-01-01

    Detta examensarbete är gjort på uppdrag av Fiber Optik Valley. Huvuduppdraget i projektet var att skapa ett fungerande betalningssystem för en hotspot och att utveckla företagets webbsida. Hotspotsystemet som baserades på en gratistjänst från Public IP, är tänkt att kunna fungera delvis autonomt utan ägarens ingripande. Företagets webbsida skapades i en Flex2-utvecklingsmiljö och produkten blev en Adobe Flash-applikation. För att få ett dynamiskt och konfigurerbart system skapades även en kon...

  3. Editing of CD1d-Bound Lipid Antigens by Endosomal Lipid Transfer Proteins

    OpenAIRE

    Zhou, Dapeng; Cantu, Carlos; Sagiv, Yuval; Schrantz, Nicolas; Kulkarni, Ashok B.; Qi, Xiaoyang; Mahuran, Don J.; Carlos R Morales; Grabowski, Gregory A.; Benlagha, Kamel; Savage, Paul; Bendelac, Albert; Teyton, Luc

    2003-01-01

    It is now established that CD1 molecules present lipid antigens to T cells, although it is not clear how the exchange of lipids between membrane compartments and the CD1 binding groove is assisted. We report that mice deficient in prosaposin, the precursor to a family of endosomal lipid transfer proteins (LTP), exhibit specific defects in CD1d-mediated antigen presentation and lack Vα14 NKT cells. In vitro, saposins extracted monomeric lipids from membranes and from CD1, thereby promoting the...

  4. Expression bakterieller Phytasen in Pflanzen

    OpenAIRE

    Dietel, Kristin

    2010-01-01

    Die Verfügbarkeit des Makroelementes Phosphor ist für Lebewesen eingeschränkt. Besonders bei der Pflanzenproduktion und der Tierernährung spielt die Phosphorverfügbarkeit eine wichtige Rolle bei der ökonomischen Nutzung der Ressourcen. In den Fokus der Wissenschaft zur Lösung des Phosphorproblems gerieten die Phytasen, da monogastrische Tiere nicht in der Lage sind das in den Pflanzensamen gespeicherte Phytat zu nutzen. Die gentechnische Veränderung von Pflanzen stellt eine effiziente Möglich...

  5. Behandlungskostenerstattung bei IVF/ICSI in Deutschland - eine aktuelle Betrachtung

    Directory of Open Access Journals (Sweden)

    Nauert R

    2007-01-01

    Full Text Available Die aktuelle Behandlungskostenerstattung bei IVF/ICSI in Deutschland wird nach wie vor durch die unterschiedlichen Versicherungsprinzipien der Körperbezogenheit in der GKV und der Verursacherbezogenheit in der PKV und damit einhergehenden Lücken der Kostenerstattung geprägt. Durch die Änderung des § 27a SGB V wurden die Leistungen der GKV vom Gesetzgeber zudem erheblich eingeschränkt, die Leistungen der PKV andererseits sind von der Rechtsprechung erheblich ausgeweitet worden, was zu einer Verschärfung der Problematik geführt hat.

  6. Das niederländische Bündnis für Arbeit und seine Wirkungen

    OpenAIRE

    Delsen, Lei

    2000-01-01

    'Jobs, Jobs und abermals Jobs' ist das politische Schlagwort in den Niederlanden. In diesem Artikel werden die Hintergründe des niederländischen "Beschäftigungswunders" erläutert und die zentrale Frage beantwortet, ob es möglich und erwünscht wäre, das "Poldermodell" in Deutschland einzuführen und zu implementieren. Gefolgert wird, dass die Übertragbarkeit des Poldermodells beschränkt ist. Es gibt beträchtliche kulturelle und institutionelle Unterschiede zwischen den beiden Ländern. Die Kehrs...

  7. Interleukin-15 treatment induces weight loss independent of lymphocytes.

    Directory of Open Access Journals (Sweden)

    Nicole G Barra

    Full Text Available Obesity is a chronic inflammatory condition characterized by activation and infiltration of proinflammatory immune cells and a dysregulated production of proinflammatory cytokines. While known as a key regulator of immune natural killer (NK cell function and development, we have recently demonstrated that reduced expression of the cytokine Interleukin-15 (IL-15 is closely linked with increased body weight and adiposity in mice and humans. Previously, we and others have shown that obese individuals have lower circulating levels of IL-15 and NK cells. Lean IL-15 overexpressing (IL-15 tg mice had an accumulation in adipose NK cells compared to wildtype and NK cell deficient obese IL-15(-/- mice. Since IL-15 induces weight loss in IL-15(-/- and diet induced obese mice and has effects on various lymphocytes, the aim of this paper was to determine if lymphocytes, particularly NK cells, play a role in IL-15 mediated weight loss. Acute IL-15 treatment resulted in an increased accumulation of NK, NKT, and CD3(+ T cells in adipose tissue of B6 mice. Mice depleted of NK and NKT cells had similar weight loss comparable to controls treated with IL-15. Finally, IL-15 treatment induces significant weight loss in lymphocyte deficient RAG2(-/-γc(-/- mice independent of food intake. Fat pad cross-sections show decreased pad size with cytokine treatment is due to adipocyte shrinkage. These results clearly suggest that IL-15 mediates weight loss independent of lymphocytes.

  8. Retinoic acid regulates CD1d gene expression at the transcriptional level in human and rodent monocytic cells.

    Science.gov (United States)

    Chen, Qiuyan; Ross, A Catharine

    2007-04-01

    CD1d belongs to a group of nonclassical antigen-presenting molecules that present glycolipid antigens and thereby activate natural killer T (NKT) cells, a subset of bifunctional T cells. Little is known so far regarding the expression and physiologic regulation of CD1d. Here we show that all-trans-retinoic acid (RA), the active metabolite of vitamin A, rapidly (1 hr after treatment) increases CD1d mRNA in human and rodent monocytic cells at a physiologic dose (10 nM). The induction is RA specific and RA receptor (RAR) dependent-RA and an RARalpha agonist, Am580, both had a pronounced positive effect, whereas the addition of RARalpha antagonist partially blocked the increase in CD1d mRNA induced by RA and Am580. The induction was also completely blocked by the presence of actinomycin D. A putative RA-response element was identified in the distal 5' flanking region of the CD1d gene, which binds nuclear retinoid receptors and was responsive to RA in both gel mobility shift assay and transient transfection assay in THP-1 cells. These results further confirmed the transcriptional regulation of RA in CD1d gene expression. Moreover, RA significantly increased alpha-galactosylceramide-induced spleen cell proliferation. These studies together provide evidence for a previously unknown mechanism of CD1d gene expression regulation by RA and suggest that RA is a significant modulator of NKT cell activation.

  9. SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease.

    Science.gov (United States)

    Rivat, Christine; Booth, Claire; Alonso-Ferrero, Maria; Blundell, Michael; Sebire, Neil J; Thrasher, Adrian J; Gaspar, H Bobby

    2013-02-14

    X-linked lymphoproliferative disease (XLP1) arises from mutations in the gene encoding SLAM-associated protein (SAP) and leads to abnormalities of NKT-cell development, NK-cell cytotoxicity, and T-dependent humoral function. Curative treatment is limited to allogeneic hematopoietic stem cell (HSC) transplantation. We tested whether HSC gene therapy could correct the multilineage defects seen in SAP(-/-) mice. SAP(-/-) murine HSCs were transduced with lentiviral vectors containing either SAP or reporter gene before transplantation into irradiated recipients. NKT-cell development was significantly higher and NK-cell cytotoxicity restored to wild-type levels in mice receiving the SAP vector in comparison to control mice. Baseline immunoglobulin levels were significantly increased and T-dependent humoral responses to NP-CGG, including germinal center formation, were restored in SAP-transduced mice.We demonstrate for the first time that HSC gene transfer corrects the cellular and humoral defects in SAP(-/-) mice providing proof of concept for gene therapy in XLP1.

  10. Primary intestinal T cell lymphomas in Indian patients - In search of enteropathic T cell lymphoma

    Directory of Open Access Journals (Sweden)

    Shet Tanuja

    2010-07-01

    Full Text Available Objective: This series of six intestinal T cell lymphomas (ITCL attempts to document enteropathy-associated T cell lymphoma (EATCL in India. Materials and Methods: A total of six ITCL were selected from 170 gastrointestinal lymphomas in last 10 years. Results: The cases studied included EATCL (4, ITCL with a CD4 positive phenotype (1 and ITCL NK/T cell type (1. Of the four EATCL, two occurred in the ileum, one in right colon and one in duodenum. In three EATCL cases, there was history of celiac disease or lactose intolerance and enteropathic changes were noted in the adjacent mucosa. These tumors had CD3+/CD8+/CD56 (+/-/CD4-/ Granzyme B+ immunophenotype. One EATCL was monomorphic small cell type (type II EATCL with a CD3+/CD8-CD56+/CD4-/ Granzyme B+ phenotype. EBER- ISH (Epstein Barr virus coded RNA′s- in situ hybridization revealed positive tumor cells in ITCL NK/T cell type and in bystander cells in three EATCL. Conclusion: ITCL are rare in Indian patients but do occur and comprise a mixture of the enteropathic and non-enteropathic subtypes.

  11. Activation mechanisms of invariant natural killer T cells (iNKTs

    Directory of Open Access Journals (Sweden)

    Baena, Andrés

    2016-01-01

    Full Text Available A great amount of knowledge on natural killer T cells (iNKTs is now available, but a consensus about their activation mechanisms has not been reached. These cells recognize different glycolipid antigens through the CD1d molecule. Such antigens may be endogenous, derived from bacteria (foreign and synthetic, the latter have been developed for clinical applications. There exists much interest in understanding how these different glycolipid compounds induce different types of polarization, but it has been difficult to reach a consensus due to the fact that responses depend on different factors such as: the nature of the molecule, the internalization process and the presentation of the glycolipids. Moreover, activation of iNKT cells is determined by the type and state of the antigen presenting cell, the co-stimulatory molecules, the transactivation mechanisms and the location of the glycolipid-CD1d complexes on the plasma membrane, such as the lipid rafts. This review explores the evidence about the factors that affect activation of iNKT cells in order to understand their immune-modulatory potential.

  12. Frequency of γδ T Cells and Invariant Natural Killer T Cells in Helicobacter Pylori-infected Patients with Peptic Ulcer and Gastric Cancer.

    Science.gov (United States)

    Shadman, Mojtaba; Rajabian, Zeinab; Ajami, Abolghasem; Hussein-Nattaj, Hadi; Rafiei, Alireza; Hosseini, Vahid; Taghvaei, Tarang; Abbasi, Ali; Tehrani, Mohsen

    2015-10-01

    To clarify the effect of γδ T cells and invariant Natural Killer T (iNKT) cells in pathophysiology of dyspeptic disorders, number of these two cells in patients with non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were compared.Patients with dyspepsia were divided into three groups of NUD, PUD, and GC according to their endoscopic and histopathological examinations. Helicobacter pylori infection was diagnosed by rapid urease test and histopathology. The number of peripheral blood CD3+TCRγδ(+) T cells and CD3+Va24Ja18+ iNKT cells were determined by flow cytometry. Immunohistochemistry (IHC) was also used for identifying the TCRγδ+ cells.Forty two patients with NUD (31.6%), 44 with PUD (33.1%), and 47 with GC (35.3%) were included in the study. The frequency of CD3+TCRγδ(+) T cells in peripheral blood of patients with GC (2.71±0.25) was significantly lower than that in NUD (3.97±0.32, pgastric cancer.

  13. Expression of activation-induced cytidine deaminase enhances the clearance of pneumococcal pneumonia: evidence of a subpopulation of protective anti-pneumococcal B1a cells.

    Science.gov (United States)

    Yamamoto, Natsuo; Kerfoot, Steven M; Hutchinson, Andrew T; Dela Cruz, Charles S; Nakazawa, Naomi; Szczepanik, Marian; Majewska-Szczepanik, Monika; Nazimek, Katarzyna; Ohana, Noboru; Bryniarski, Krzysztof; Mori, Tsutomu; Muramatsu, Masamichi; Kanemitsu, Keiji; Askenase, Philip W

    2016-01-01

    We describe a protective early acquired immune response to pneumococcal pneumonia that is mediated by a subset of B1a cells. Mice deficient in B1 cells (xid), or activation-induced cytidine deaminase (AID(-/-) ), or invariant natural killer T (iNKT) cells (Jα18(-/-) ), or interleukin-13 (IL-13(-/-) ) had impaired early clearance of pneumococci in the lung, compared with wild-type mice. In contrast, AID(-/-) mice adoptively transferred with AID(+/+) B1a cells, significantly cleared bacteria from the lungs as early as 3 days post infection. We show that this early bacterial clearance corresponds to an allergic contact sensitivity-like cutaneous response, probably due to a subpopulation of initiating B1a cells. In the pneumonia model, these B1a cells were found to secrete higher affinity antigen-specific IgM. In addition, as in contact sensitivity, iNKT cells were required for the anti-pneumococcal B1a cell initiating response, probably through early production of IL-13, given that IL-13(-/-) mice also failed to clear infection. Our study is the first to demonstrate the importance of AID in generating an appropriate B1a cell response to pathogenic bacteria. Given the antibody affinity and pneumonia resistance data, natural IgM produced by conventional B1a cells are not responsible for pneumonia clearance compared with the AID-dependent subset. PMID:26456931

  14. Correlation between natural killer T cell expression and virological response to treatment with peg-interferon alfa-2a in patients with HBeAg-positive chronic hepatitis B%聚乙二醇干扰素治疗HBeAg阳性慢性乙型肝炎患者外周血NKT细胞的变化及疗效预测

    Institute of Scientific and Technical Information of China (English)

    黄芳; 龚环宇; 鲁猛厚

    2013-01-01

    目的 研究聚乙二醇干扰素α-2a(Peg-INFα-2a)治疗乙型肝炎e抗原(HBeAg)阳性慢性乙型肝炎(CHB)患者,其外周血NKT细胞表达率和疗效预测相关性.方法 选取 2010年1-12月在中南大学湘雅三医院住院和门诊接受治疗的HBeAg阳性CHB患者63例,予Peg-INFα-2a 18 MIU肌内注射,1次/周,共48周.检测各时段外周血NKT数量占外周血T淋巴细胞的百分比、血清乙型肝炎5项定量及乙型肝炎病毒(HBV) DNA载量.结果 Peg-INFα-2a治疗HBeAg阳性CHB患者48周后,显效(完全病毒学应答)26例,有效(部分病毒学应答)21例,无效(无病毒学应答)16例.外周血NKT 细胞占T淋巴细胞百分比:显效组治疗前及治疗后4、8、12、16、24周,较有效组和无效组均明显升高(均P<0.01);在治疗48周和停药24周,显效组较有效组NKT表达水平明显升高(分别t=32.0,P<0.01;t=27.6,P<0.01).显效组治疗后前4周,NKT表达水平上升速度最快,12周时达最高峰,其后逐渐下降,到24周比治疗前水平稍高,一直维持到48周;有效组12周时NKT表达水平达最高峰,较治疗前显著增高(t=12.83,P<0.05).显效组患者肝功能基本在12周左右完全恢复正常,且持续维持在正常水平,其HBV DNA载量亦逐步下降;而有效组和无效组患者的肝功能波动在(1~2)×ULN.监测至停药24周后,共有27例患者出现HBeAg血清学转换.结论 Peg-INFα-2a治疗HBeAg阳性CHB患者,其外周血中NKT的表达对疗效有一定预测作用.%Objective To study the correlation between expression of natural killer T (NKT) cells and virological response to treatment with peg-interferon alfa-2a (Peg- INFα-2a)in patients with HBeAg-positive chronic hepatitis B (CHB). Methods A cohort of 63 HBeAg-positive CHB inpatients and outpatients in a hospital between January and December 2010 were treated with 18MIU Peg-IFNα-2a once a week lor 48 weeks. The percentage of NKT cells in T lymphocytes, five serological markers of

  15. Comparison of Human Neonatal and Adult Blood Leukocyte Subset Composition Phenotypes.

    Science.gov (United States)

    Prabhu, Savit B; Rathore, Deepak K; Nair, Deepa; Chaudhary, Anita; Raza, Saimah; Kanodia, Parna; Sopory, Shailaja; George, Anna; Rath, Satyajit; Bal, Vineeta; Tripathi, Reva; Ramji, Siddharth; Batra, Aruna; Aggarwal, Kailash C; Chellani, Harish K; Arya, Sugandha; Agarwal, Nidhi; Mehta, Umesh; Natchu, Uma Chandra Mouli; Wadhwa, Nitya; Bhatnagar, Shinjini

    2016-01-01

    The human peripheral leukocyte subset composition depends on genotype variation and pre-natal and post-natal environmental influence diversity. We quantified this composition in adults and neonates, and compared the median values and dispersal ranges of various subsets in them. We confirmed higher frequencies of monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells in neonatal umbilical cord blood. Unlike previous reports, we found higher frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in neonates. We characterized monocyte subsets and dendritic cell (DC) subsets in far greater detail than previously reported, using recently described surface markers and gating strategies and observed that neonates had lower frequencies of patrolling monocytes and lower myeloid dendritic cell (mDC):plasmacytoid DC (pDC) ratios. Our data contribute to South Asian reference values for these parameters. We found that dispersal ranges differ between different leukocyte subsets, suggesting differential determination of variation. Further, some subsets were more dispersed in adults than in neonates suggesting influences of postnatal sources of variation, while some show the opposite pattern suggesting influences of developmental process variation. Together, these data and analyses provide interesting biological possibilities for future exploration. PMID:27610624

  16. Assessment of Some Immune Parameters in Occupationally Exposed Nuclear Power Plants Workers

    Science.gov (United States)

    Panova, Delyana; Djounova, Jana; Rupova, Ivanka; Penkova, Kalina

    2015-01-01

    The purpose of this article is to analyze the results of a 10-year survey of the radiation effects of some immune parameters of occupationally exposed personnel from the Nuclear Power Plant “Kozloduy”, Bulgaria. 438 persons working in NPP with cumulative doses between 0.06 mSv and 766.36mSv and a control group with 65 persons were studied. Flow cytometry measurements of T, B, natural killer (NK) and natural killer T (NKT) cell lymphocyte populations were performed. Data were interpreted with regard to cumulative doses, length of service and age. The average values of the studied parameters of cellular immunity were in the reference range relative to age and for most of the workers were not significantly different from the control values. Low doses of ionizing radiation showed some trends of change in the number of CD3+CD4+ helper-inducer lymphocytes, CD3+ CD8+ and NKT cell counts. The observed changes in some of the studied parameters could be interpreted in terms of adaptation processes at low doses. At doses above 100–200 mSv, compensatory mechanisms might be involved to balance deviations in lymphocyte subsets. The observed variations in some cases could not be attributed only to the radiation exposure because of the impact of a number of other exogenous and endogenous factors on the immune system. PMID:26675014

  17. Cell-Mediated Immunity Imbalance in Patients with Intrahepatic Cholestasis of Pregnancy

    Institute of Scientific and Technical Information of China (English)

    Bin Ling; Fengqiu Yao; Ying Zhou; Zhengzheng Chen; Guodong Shen; Yuanyuan Zhu

    2007-01-01

    Decidual lymphocytes may mediate fetal trophoblast recognition and regulate maternal immune reaction and play an essential role in the maintenance of normal pregnancy. The aim of this study was to compare the percentage of T cells, natural killer (NK) cells and natural killer T (NKT) cells within decidual parietalis of normal pregnant controls (NP) and patients with intraheptic cholestasis of pregnancy (ICP), and to investigate the production of interleukin-4 (IL-4), interferon-γ (IFN-γ) in the culture supernatant of decidual parietalis mononuclear cells (DPMCs). Compared with controls, the decidua parietalis from ICP were characterized with significant increased percentages of CD3-CD56+ cells, CD3+CD56+ cells, CD56+CD16+ cells, CD56+CD16- cells, CD56+NKG2D+ cells, and the significant decreased percentages of CD3+ cells, CD3+CD4+ cells. There were no differences found for the percentage of CD3+CD8+ cells, CD56+NKG2A+ cells between control and study group. In addition, the enhanced concentration of IFN-γ was presented in culture supernatant of DPMCs from ICP. It was suggested that the increased NK cells, NKT cells and the decreased T cells in the decidual parietalis and over-secretion of IFN-γ could be correlated with the pathophysiology of ICP patients.

  18. Advance of Cellular Immunotherapy in Clinical and Translational Medicine of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    YAN Fei; YU Shao-rong; FENG Ji-feng

    2016-01-01

    Lung cancer is one of the most common cancers and ranks the ifrst in the mortality worldwide. The core of immunotherapy, especially cellular immunotherapy, is to activate the T cell-mediated tumor-killing effect in patients with tumors, so as to increase their anti-tumor effect. Surgery and radio- and chemotherapy cannot radically eliminate cancerous cells, but immunotherapy is an important supplementary method in killing tumor stem cells and non-proliferating cells. Cellular immunotherapy contains dendritic cells (DC), cytokine-induced killer (CIK), DC-CIK, natural killer T cells (NKT) and γδ T cells, which provides new techniques for the comprehensive treatment of lung cancer. Using CIK combined with DC, radiochemotherapy, radiofrequency ablation and monomers of Chinese medicine to induce CIK cells that directionally migrate to cancerous nest can increase tumor-killing ability and immunoregulatory ability of CIK cells, reduce adverse and toxic reactions and increase patients’ quality of life, and NKT cell and γδ T cell therapies have also been gradually perfected and promoted in clinical translation. This study mainly introduced the clinical translation of DC vaccines, CIK cells and DC-CIK treatment for lung cancer, hoping to provide new pathways and reference for the clinical treatment of lung cancer.

  19. A single subset of dendritic cells controls the cytokine bias of natural killer T cell responses to diverse glycolipid antigens.

    Science.gov (United States)

    Arora, Pooja; Baena, Andres; Yu, Karl O A; Saini, Neeraj K; Kharkwal, Shalu S; Goldberg, Michael F; Kunnath-Velayudhan, Shajo; Carreño, Leandro J; Venkataswamy, Manjunatha M; Kim, John; Lazar-Molnar, Eszter; Lauvau, Gregoire; Chang, Young-tae; Liu, Zheng; Bittman, Robert; Al-Shamkhani, Aymen; Cox, Liam R; Jervis, Peter J; Veerapen, Natacha; Besra, Gurdyal S; Porcelli, Steven A

    2014-01-16

    Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α(+) DEC-205(+) dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α(+) dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses.

  20. 颅脑损伤患者自然杀伤T细胞与性激素的相关性及其临床意义分析%Role of natural killer cells and their correlation with sexual hormones for patients suffering from craniocerebral trauma

    Institute of Scientific and Technical Information of China (English)

    陈成

    2013-01-01

    目的 探索颅脑损伤患者自然杀伤T细胞与性激素的相关性及其临床意义.方法 收集轻、中及重度颅脑损伤患者各30例,并选择20例健康体检者作为对照,在不同时间点采用流式细胞术检测自然杀伤T细胞(NKT)及其细胞因子白介素4(IL-4)及γ-干扰素(IFN-γ)含量,同时检测其性激素水平,并分析上述指标的相关性.结果 与健康组比较,轻、中及重度颅脑损伤患者的NKT及IFN-γ均明显降低,且与损伤程度相关,呈现轻>中>重关系(P<0.05).在患者就诊即刻、伤后24h及72h的三个时间点内,三组患者的NKT及IFN-γ均呈进行性下降趋势(P<0.05).轻中重度颅脑损伤患者的IL-4高于健康对照组,且随着病情进展IL-4含量进行性升高(P<0.05).雌二醇、孕酮及睾酮三者的变化趋势均与NKT及IFN-γ相反,其含量表现为轻<中<重,其随着时间的推演其含量进行性下降(P<0.05).相关性分析显示NKT与IFN-γ呈正比,而与IL-4呈反比;NKT及IFN-γ与性激素三项均呈反比,IL-4与性激素三项呈正比,以上任意两者的相关性分析均有统计学意义(P<0.05).结论 NKT及IFN-γ是脑损伤的一个保护性因素,且与性激素含量呈负相关性;而IL-4是颅脑损伤后的不利因素,后者可介导脑损伤后的体液免疫反应,从而加重病情.%Objective To explore the Role of natural killer cells and their correlation with sexual hormones for patients suffering from craniocerebral trauma.Methods The data of light,medium and severe craniocerebral injury patients,and choose the 30 cases and cases of healthy check-up person as a comparison,in different time point using flow cytometry test natural killer T cells (NKT) and cytokine interleukin 4 (IL-4) and reported interferon (IFN ppar-gamma) content,at the same time detection the sex hormone level,and analysis of the correlation between the index.Results Compared with the healthy group,light,medium and severe

  1. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    Full Text Available Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer for harnessing the adjuvant potential of natural killer T (NKT cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  2. The Regulatory Effect of Natural Killer Cells: Do "NK-reg Cells" Exist?

    Institute of Scientific and Technical Information of China (English)

    Cai Zhang; Jian Zhang; Zhigang Tian

    2006-01-01

    The most important progress in immunology in the last decade is the description of regulatory lymphocytes, among which Treg cells and regulatory NKT cells are much attractive to not only immunologists but also almost all biomedical researchers. Meanwhile, it is noted that NK cells are not only "Killers" but also regulate innate and adaptive immunity, especially in early stage, by secreting cytokines and cell-cell contact. In this review, we are going to briefly summarize the progresses in regulatory lymphocytes including T cells (Treg, Tr1, Th3), NKT cells and NK cells, and then extensively introduce the positive regulatory function of NK cells in both normal immune response and in disease condition (tumor, infection and autoimmunity), and finally, to focus on the most latest progression in the negative regulatory effects of NK cells on normal and pathogenic immune response. In conclusion, we speculate that a "regulatory NK (NK-reg)" cell subset exist and need to explore. Cellular & Molecular Immunology. 2006;3(4):241-254.

  3. 3-fluoro- and 3,3-difluoro-3,4-dideoxy-KRN7000 analogues as new potent immunostimulator agents: total synthesis and biological evaluation in human invariant natural killer T cells and mice.

    Science.gov (United States)

    Hunault, Julie; Diswall, Mette; Frison, Jean-Cédric; Blot, Virginie; Rocher, Jézabel; Marionneau-Lambot, Séverine; Oullier, Thibauld; Douillard, Jean-Yves; Guillarme, Stéphane; Saluzzo, Christine; Dujardin, Gilles; Jacquemin, Denis; Graton, Jérôme; Le Questel, Jean-Yves; Evain, Michel; Lebreton, Jacques; Dubreuil, Didier; Le Pendu, Jacques; Pipelier, Muriel

    2012-02-01

    We propose here the synthesis and biological evaluation of 3,4-dideoxy-GalCer derivatives. The absence of the 3- and 4-hydroxyls on the sphingoid base is combined with the introduction of mono or difluoro substituent at C3 (analogues 8 and 9, respectively) to evaluate their effect on the stability of the ternary CD1d/GalCer/TCR complex which strongly modulate the immune responses. Biological evaluations were performed in vitro on human cells and in vivo in mice and results discussed with support of modeling studies. The fluoro 3,4-dideoxy-GalCer analogues appears as partial agonists compared to KRN7000 for iNKT cell activation, inducing T(H)1 or T(H)2 biases that strongly depend of the mode of antigen presentation, including human vs mouse differences. We evidenced that if a sole fluorine atom is not able to balance the loss of the 3-OH, the presence of a difluorine group at C3 of the sphingosine can significantly restore human iNKT activation.

  4. Neutralization of the Principal Toxins from the Venoms of Thai Naja kaouthia and Malaysian Hydrophis schistosus: Insights into Toxin-Specific Neutralization by Two Different Antivenoms.

    Science.gov (United States)

    Tan, Kae Yi; Tan, Choo Hock; Fung, Shin Yee; Tan, Nget Hong

    2016-04-01

    Antivenom neutralization against cobra venoms is generally low in potency, presumably due to poor toxin-specific immunoreactivity. This study aimed to investigate the effectiveness of two elapid antivenoms to neutralize the principal toxins purified from the venoms of the Thai monocled cobra (Naja kaouthia, Nk-T) and the Malaysian beaked sea snake (Hydrophis schistosus, Hs-M). In mice, N. kaouthia Monovalent Antivenom (NKMAV) neutralization against Nk-T long neurotoxin (LNTX) and cytotoxin was moderate (potency of 2.89-6.44 mg toxin/g antivenom protein) but poor against the short neurotoxin (SNTX) (1.33 mg/g). Its cross-neutralization against Hs-M LNTX of Hs-M is compatible (0.18 mg/g) but much weaker against Hs-M SNTX (0.22 mg/g). Using CSL (Seqirus Limited) Sea Snake Antivenom (SSAV), we observed consistently weak neutralization of antivenom against SNTX of both species, suggesting that this is the limiting factor on the potency of antivenom neutralization against venoms containing SNTX. Nevertheless, SSAV outperformed NKMAV in neutralizing SNTXs of both species (0.61-2.49 mg/g). The superior efficacy of SSAV against SNTX is probably partly attributable to the high abundance of SNTX in sea snake venom used as immunogen in SSAV production. The findings indicate that improving the potency of cobra antivenom may be possible with a proper immunogen formulation that seeks to overcome the limitation on SNTX immunoreactivity. PMID:27023606

  5. Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus

    Directory of Open Access Journals (Sweden)

    Carlos Wong-Baeza

    2015-01-01

    Full Text Available Systemic lupus erythematosus is characterized by dysregulated activation of T and B cells and autoantibodies to nuclear antigens and, in some cases, lipid antigens. Liposomes with nonbilayer phospholipid arrangements induce a disease resembling human lupus in mice, including IgM and IgG antibodies against nonbilayer phospholipid arrangements. As the effect of these liposomes on the innate immune response is unknown and innate immune system activation is necessary for efficient antibody formation, we evaluated the effect of these liposomes on Toll-like receptor (TLR signaling, cytokine production, proinflammatory gene expression, and T, NKT, dendritic, and B cells. Liposomes induce TLR-4- and, to a lesser extent, TLR-2/TLR-6-dependent signaling in TLR-expressing human embryonic kidney (HEK cells and bone marrow-derived macrophages. Mice with the lupus-like disease had increased serum concentrations of proinflammatory cytokines, C3a and C5a; they also had more TLR-4-expressing splenocytes, a higher expression of genes associated with TRIF-dependent TLR-4-signaling and complement activation, and a lower expression of apoptosis-related genes, compared to healthy mice. The percentage of NKT and the percentage and activation of dendritic and B2 cells were also increased. Thus, TLR-4 and TLR-2/TLR-6 activation by nonbilayer phospholipid arrangements triggers an inflammatory response that could contribute to autoantibody production and the generation of a lupus-like disease in mice.

  6. A self-adjuvanting vaccine induces cytotoxic T lymphocytes that suppress allergy.

    Science.gov (United States)

    Anderson, Regan J; Tang, Ching-wen; Daniels, Naomi J; Compton, Benjamin J; Hayman, Colin M; Johnston, Karen A; Knight, Deborah A; Gasser, Olivier; Poyntz, Hazel C; Ferguson, Peter M; Larsen, David S; Ronchese, Franca; Painter, Gavin F; Hermans, Ian F

    2014-11-01

    Epitope-based peptide vaccines encompass minimal immunogenic regions of protein antigens to allow stimulation of precisely targeted adaptive immune responses. However, because efficacy is largely determined by the functional status of antigen-presenting cells (APCs) that acquire and present peptides to cells of the adaptive immune system, adjuvant compounds are needed to enhance immunogenicity. We present here a vaccine consisting of an allergen-derived peptide conjugated to a prodrug of the natural killer-like T (NKT) cell agonist α-galactosylceramide, which is highly effective in reducing inflammation in a mouse model of allergic airway inflammation. Unlike other peptide-adjuvant conjugates that directly activate APCs through pattern recognition pathways, this vaccine encourages third-party interactions with NKT cells to enhance APC function. Therapeutic efficacy was correlated with marked increases in the number and functional activity of allergen-specific cytotoxic T lymphocytes (CTLs), leading to suppression of immune infiltration into the lungs after allergen challenge in sensitized hosts. PMID:25282504

  7. 1-Methyl-4-phenyl-pyridinium time-dependently alters expressions of oxoguanine glycosylase 1 and xeroderma pigmentosum group F protein in PC12 cells%1-甲基-4-苯基吡啶时程依赖性改变PC12细胞内氧基-鸟嘌呤DNA糖苷酶和着色性干皮病蛋白F的表达

    Institute of Scientific and Technical Information of China (English)

    刘红梅; 杨善争; 孙凤艳

    2010-01-01

    目的 探讨离体条件下DNA剪切修复相关蛋白酶氧基-鸟嘌呤DNA糖苷酶(OGG1)和着色性干皮病蛋白F(XPF)是否参与帕金森病(PD)的病理过程.方法 用1 mmol/L 1-甲基-4-苯基吡啶(MPP+)处理PC12细胞不同时间,诱导细胞产生DNA氧化损伤,建立PD细胞模型.在此模型上,采用MTT法检测细胞活力;采用8-氧基-7,8-双氢脱氧鸟嘌呤(8-oxodG)免疫细胞化学技术检测细胞DNA氧化损伤;用Western blot技术检测细胞内OGG1和XPF 的蛋白表达水平.结果 MPP+时程依赖性地降低细胞活力,18 h和24 h后细胞活力分别降至对照组的78.6%和70.3%.MPP+显著增加了8-oxodG免疫阳性反应,在3 h时8-oxodG主要分布于细胞质,在24 h时其主要位于细胞核内.此外,MPP+显著改变了OGG1和XPF的蛋白表达水平.在MPP+处理1 h后,OGG1和XPF蛋白表达水平均显著上调,分别于3 h和18 h达到顶峰,随后依次下降,且OGG1的峰值几乎是XPF的两倍.结论MPP+时程依赖性地增加了PC12细胞内XPF和OGG1的表达水平.本研究提示,在MPP+致PD的病理模型早期,碱基切除修复和核苷酸剪切修复可能被代偿性地激活.

  8. 77例T细胞非霍奇金淋巴瘤的临床病理特点和免疫表型分析%The clinicopathologic features and immunophenotypes of T-cell non-Hodgkin's lymphoma: an analysis of 77 cases

    Institute of Scientific and Technical Information of China (English)

    赵伟; 陈陆俊; 田波; 谈炎; 鲁常青

    2012-01-01

    Objective To study the clinicopathologic features and immunophenotypes of T-cell non-Hodgkin's lymphoma. Methods Seventy-seven of T-cell non-Hodgkin s lymphomas were studied by light microscopy and immunohistochemistry. All cases were reclassified according to the new WHO classification of lymphomas. Results Of 77 T-cell non-Hodgkin's lymphomas,32(41. 6%) cases were extranodal NK/T cell lymphomas of nasal type,20(26. 0%) cases were nonspecific peripheral T cell lymphomas, 11 (14. 3%) cases were anaplastic large cell lymphomas and 9(11.7%) cases were precursor T lymphoblastic lymphomas. Conclusion Among T-cell non-Hodgkin's lymphomas, extranodal NK/T cell lymphoma of nasal type is the most common subtype. The other main subtypes conclude nonspecific peripheral T cell lymphomas, anaplastic large cell lymphomas and precursor T lymphoblastic lymphomas. The patients with extranodal NK/T cell lymphomas of nasal type have poor prognosis, while those with anaplastic large cell lymphomas have favorable prognosis.%目的 探讨T细胞非霍奇金淋巴瘤的临床病理特点和免疫表型.方法 对77例T细胞非霍奇金淋巴瘤进行苏木素和伊红染色(HE)和免疫组织化学检查,按WHO 2008年《造血和淋巴 组织肿瘤的病理学和遗传学》标准进行分类.结果 77例T细胞非霍奇金淋巴瘤中,鼻型结外NK/T细胞淋巴瘤32例(41.6%),非特异性外周T细胞淋巴瘤20例(26.0%),间变性大细胞淋巴瘤11例(14.3%),前驱T淋巴细胞淋巴瘤9例(11.7%).结论 T细胞非霍奇金淋巴瘤中,最常发生的亚型是鼻型结外NK/T细胞淋巴瘤,其次为非特异性外周T细胞淋巴瘤、间变性大细胞淋巴瘤和前驱T淋巴细胞淋巴瘤.其中,鼻型结外NK/T细胞淋巴瘤预后较差,而间变性大细胞淋巴瘤预后相对 较好.

  9. Isolation of murine hepatic lymphocytes using mechanical dissection for phenotypic and functional analysis of NK1.1 + cells

    Institute of Scientific and Technical Information of China (English)

    Zhong-Jun Dong; Hai-Ming Wei; Rui Sun; Bin Gao; Zhi-Gang Tian

    2004-01-01

    AIM: To choose an appropriate methods for the isolation of hepatic lymphocytes between the mechanical dissection and the enzymatic digestion and investigate the effects of two methods on phenotype and function of hepatic lymphocytes.METHODS: Hepatic lymphocytes were isolated from untreated, poly (I:C)-stimulated or ConA-stimulated mice using the two methods, respectively. The cell yield per liver was evaluated by direct counting under microscope.Effects of digestive. enzymes on the surface markers involved in hepatic lymphocytes were represented by relative change rate [(percentage of post-digestion -percentage of pre-digestion)/percentage of pre-digestion].Phenotypic analyses of the subpopulations of hepatic lymphocytes and intracellular cytokines were detected by flow cytometry. The cytotoxicity of NK cells from wild C57BL/6 or poly (I:C)-stimulated C57BL/6 mice was analyzed with a 4-h 51Cr release assay.RESULTS: NK1.1+ cell markers, NK1.1 and DX5, were significantly down-expressed after enzymatic digestion and their relative change rates were about 28% and 32%,respectively. Compared with the enzymatic digestion, the cell yield isolated from unstimulated, poly (I:C)-treated or ConA-treated mice by mechanical dissection was not significantly decreased. Hepatic lymphocytes isolated by the mechanical dissection comprised more innate immune cells like NK, NKT and γδ cells in normal C57BL/6 mice.After poly (I:C) stimulation, hepatic NK cells rose to about 35%, while NKT cells simultaneously decreased. Following ConA injection, the number of hepatic NKT cells was remarkably reduced to 3.67%. Higher ratio of intracellular IFN-γ+(68%) or TNF-α+(15%) NK1.1+ cells from poly (I:C)-treated mice was obtained using mechanical dissection method than control mice. There was no difference in viability between the mechanical dissection and the enzymatic digestion, and hepatic lymphocytes obtained with the two methods had similar cytotoxicity against YAC-1cells

  10. Suppressive Effect of Juzen-Taiho-To on Lung Metastasis of B16 Melanoma Cells In Vivo

    Directory of Open Access Journals (Sweden)

    Takako Matsuda

    2011-01-01

    Full Text Available Juzen-Taiho-To (JTT is well known to be one of Kampo (Japanese herbal medicine consisted of 10 component herbs and used for the supplemental therapy of cancer patients with remarkably success. However, the precise mechanisms by which JTT could favorably modify the clinical conditions of cancer patients are not well defined. The present study, therefore, was undertaken to examine the possible mechanisms of JTT on prevention of cancer metastasis using experimental mouse model. JTT was well mixed with rodent chow at concentrations of either 0.2 or 1.0%, and administered orally ad libitum, which was started 1 week before tumor cell injection and continue throughout the experiment. Oral administration of JTT at concentration 0.2 and 1.0% into C57BL/6 male mice significantly inhibited tumor metastasis in lungs, which was induced by the intravenous injection of 2 × 105 B16 melanoma cell. JTT at a concentration of 1.0% also significantly suppressed lung metastasis of B16 melanoma cell from hind footpad in C57BL/6 mice. In the second part of experiments, the influence of the depression of natural killer (NK cell, natural killer T (NKT cell and several types of cytokines on JTT-mediated inhibition of tumor cell metastasis. Intraperitoneal injection of anti asialo-GM1 antibody against NK cells and anti NK-1.1 monoclonal antibody (mAb to NKT cells abrogated the inhibitory action of JTT on lung metastasis of B16 melanoma cells. Although intraperitoneal administration of anti-IFN-γ mAb scarcely affected the inhibitory action of JTT on tumor cell metastasis, injection of amrinone, which used for IL-12 suppression, significantly decreased the ability of JTT to prevent tumor cell metastasis. These results strongly suggest that oral administration of JTT caused increase in the production of IL-12, which is responsible for the activation of both NK cell and NKT cell, in the lungs and results in inhibition of B16 melanoma cell metastasis in the lungs.

  11. Etiska dilemman vid fosterdöd : Utformande av ett simuleringscase för blivande barnmorskor

    OpenAIRE

    Grönlund, Regina; Svenfelt, Sofia

    2015-01-01

    Att arbeta som barnmorska är ofta förknippat med stora förväntningar och glädje. Barnmorskorna stöter dock också på fall där inte förlossningen går som man hade tänkt sig och barnen föds döda. Det krävs mycket av barnmorskan för att kunna bemöta dessa mödrar. Syftet med denna systematiska litteraturstudie var att lyfta fram betydelsen av etiken och att öka kunskapen i barnmorskans roll och handlande vid fosterdöd. Arbetet var ett beställningsarbete från Arcadas projekt för kunskapsutveckling ...

  12. Orphan diseases of the nose and paranasal sinuses: Pathogenesis – clinic – therapy

    Directory of Open Access Journals (Sweden)

    Laudien, Martin

    2015-12-01

    Full Text Available Rare rhinological diseases are a diagnostic challenge. Sometimes it takes months or even years from the primary manifestation of the disease until the definitive diagnosis is establibshed. During these times the disease proceeds in an uncontrolled or insufficiently treated way. (Irreversible damage results and sometimes life-threatening situations occur. The unexpected course of a (misdiagnosed disease should lead to further diagnostic reflections and steps in order to detect also rare diseases as early as possible.The present paper discusses granulomatous diseases of the nose and paranasal sinuses caused by mycobacteria, treponema, Klebsiella, fungi, and protozoa as well as vasculitis, sarcoidosis, rosacea, cocaine-induced midline destruction, nasal extranodal NK/T cell lymphoma, and cholesterol granuloma. Furthermore, diseases with disorders of the mucociliary clearance such as primary ciliary dyskinesia and cystic fibrosis are presented, taking into consideration the current literature.

  13. Primary nasopharyngeal non-Hodgkin lymphoma and its relationship with Epstein-Barr virus infection

    Institute of Scientific and Technical Information of China (English)

    张彬; 宗永生; 何洁华; 钟碧玲; 林素暇

    2003-01-01

    Objectives To investigate the immunophenotypes of primary nasopharyngeal non-Hodgkin lymphoma (NPL) and their relationship to Epstein-Barr virus (EBV) infection.Methods The clinical data and biopsies of 73 patients with NPL were collected in Guangzhou. In situ hybridization was performed to detect the EBV-encoded small non-polyadenylated nuclear RNAs (EBERs) on biopsy slides. Immunohistochemistry was used to classify the immunophenotypes of NPL and detect EBV antigen expression. Results Forty-four (60.27%) of the 73 NPLs were of B cell lineage (CD79α+/CD3-/CD56-) while the 29 others (39.73%) were of non-B cell lineage. Seventy-three NPLs could be classified into 3 major immunophenotypes: B cell (CD79α+/CD3-/CD56-, 44 cases), peripheral T cell (CD79α-/CD3+/CD56-,22) and NK/T cell (CD79α-/CD3+/CD56+, 7). The percentages of EBV infection differed among the 3 major immunophenotypes (B cell: 11.36%, 5/44; peripheral T cell: 81.82%, 18/22; NK/T cell: 100%, 7/7). Both CD56-positive and CD56-negative immunophenotypes could further be divided into 4 subtypes: CD8-/CD4-,CD8+/CD4-, CD8-/CD4+ and CD8+/CD4+. All the CD8-/CD4- NPLs with CD56-positivity (7) or CD56-negativity (2) were infected with EBV. The neoplastic cells of a nasopharyngeal Burkitt’s lymphoma expressed EBV nuclear antigen 1 (EBNA1) and EBV RNA (EBERs) only. In the other 29 EBV-infected NPLs, most of the lymphoma cells harboring EBV also expressed EBNA1 and EBERs; 21 of the 29 NPLs had a considerable number of neoplastic cells expressing latent membrane protein 1 (LMP1) (21/29, 72.41%) and 23 of 29 NPLs expressed latent membrane protein 2A (LMP2A) (23/29, 79.31%). A few lymphoma cells in 17 (17/29, 58.62%), 23 (23/29, 79.31%) and 22 NPLs (22/29, 75.86%) expressed Zta (Bam HI Z transactivator), viral capsid antigen (VCA) and membrane antigen (MA), respectively.Conclusions The prevalence ratio of the 3 immunophenotypes, namely, B cell, peripheral T cell and NK/T cell lymphoma, is about 6∶3∶1. However

  14. Prefrontal korteks asimetrisinin kantitatif EEG ile Değerlendirilmesi

    OpenAIRE

    ÇİÇEK, Metehan

    1998-01-01

      İman bilişiminde önemli role sahip olan prefrontal korteksin işlevleri henüz tam olarak aydınktılamamıştır. Posterior kortikal alanların asimetrik aktivasyonu hakkında daha çok bilgimiz olmasına rağmen anterior kortikal alanların asimetrik işlevleri araştırmaya açıktır. Özellikle prefrontal korteksin işleyen bellek işlevi sırasındaki asimetrik aktivasyonuna el tercihi ve cinsiyetin etkisi açıklık kazanmamıştır. Araştırmada EEG alfa asimetrisi kullanılarak, pref...

  15. Stedssans

    DEFF Research Database (Denmark)

    Ringgaard, Dan

    med erindring og historie, til i højere grad at være et knudepunkt for globale kredsløb.  Forfatteren søger svar på sine spørgsmål til stedet i litteraturen, i hvad der er tænkt og skrevet om stedet, og på stederne selv. I essays om blandt andet politikommissær Maigret, Graham Greenes eksotiske...... spioner, Thomas Bobergs rejsebøger, Inger Christensens og Morten Søndergaards digte, om litteraturens landmålere og korttegnere, om stedets teori – og på virkelige steder i Bahia, Brasilien: en lufthavn og et hotel, en storby, en mineby der nu ernærer sig ved turisme, og en palmeø udvikles en sans...

  16. Arrangerede venskaber

    DEFF Research Database (Denmark)

    Prieur, Annick; Henriksen, Lars Skov

    eller under tilsyn, skal der udarbejdes en handlingsplan for fremtiden, og mentorerne er tiltænkt en rolle i forbindelse med realiseringen af disse planer. Mentorerne har tit også anden etnisk baggrund end dansk. Ordningen er ny, og Direktoratet ønskede en evalu­ering med henblik på at vurdere...... ordningens kvalitet. Ordningen bygger på en forestilling om, at disse unge med anden etnisk baggrund tit oplever konflikter mellem dansk kultur og hjemlig kultur, og den bærende idé er, at den unge skal få hjælp fra en positiv rollemodel til at lære at takle sine problemer og i højere grad tage ansvar for...

  17. Clinical effectiveness and cost-effectiveness of central venous catheters treated with Minocycline and Rifampicin in preventing bloodstream infections in intensive care patients [Medizinische Wirksamkeit und Kosteneffektivität von Minocyclin/Rifampicin-beschichteten zentralvenösen Kathetern zur Prävention von Blutbahninfektionen bei Patienten in intensivmedizinischer Betreuung

    Directory of Open Access Journals (Sweden)

    Neusser, Silke

    2012-10-01

    Full Text Available [english] The use of central venous catheters coated with antibiotics can avoid bloodstream infections with intensive care patients. This is the result of a scientific examination which has been published by the DIMDI. Costs could be also saved in this way. However, according to the authors, the underlying studies do not allow absolutely valid statements.[german] Der Einsatz bestimmter Antibiotika-beschichteter Venenkatheter kann bei Intensivpatienten Blutbahninfektionen vermeiden. So das Ergebnis einer wissenschaftlichen Untersuchung, die das DIMDI veröffentlicht hat. Auch ließen sich damit Kosten einsparen. Allerdings erlauben, laut den Autoren, die zugrunde gelegten Studien keine uneingeschränkt gültigen Aussagen.

  18. It cannot kill a mouse, though it can heal a man

    DEFF Research Database (Denmark)

    Alstrup, Aage Kristian Olsen

    2015-01-01

    Selvom dyreforsøg har været altafgørende for forståelsen af menneskets fysiologi og sygdomme, så er der også ret mange eksempler på, at dyreforsøg har vildledt forskerne. Blandt forskere florerer der en påstand om, at hvis Alexander Fleming havde testet penicillin på gnavere, så ville de være døde...... tarmfloraen og i sidste ende dø. Det er derfor oplagt at forestille sig, at marsvinene ville være døde, hvis Alexander Fleming havde testet den nyopdagede penicillin på dem, og at han derfor ville have tænkt, at penicillin er ubrugelig til bekæmpelse af infektionssygdomme. Der er dog lige den hage ved...

  19. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis

    Science.gov (United States)

    Fransén-Pettersson, Nina; Duarte, Nadia; Nilsson, Julia; Lundholm, Marie; Mayans, Sofia; Larefalk, Åsa; Hannibal, Tine D.; Hansen, Lisbeth; Schmidt-Christensen, Anja; Ivars, Fredrik; Cardell, Susanna; Palmqvist, Richard; Rozell, Björn

    2016-01-01

    Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders. PMID:27441847

  20. Zur Konstruktion von Rollen in der computervermittelten Kommunikation und Kooperation

    Directory of Open Access Journals (Sweden)

    Andreas Langlotz

    2005-11-01

    Full Text Available Dieser Beitrag analysiert aus linguistisch-diskursanalytischer Perspektive die gesteuerte und ungesteuerte Konstruktion von Team-Rollen in einem virtuellen Seminar (blended learning. In Abgrenzung zu bestimmten sozialpsychologischen Ansätzen wird argumentiert, dass die Kommunikation sozialer Information im virtuellen Raum nicht grundsätzlich eingeschränkt ist. Vielmehr bedienen sich die Teilnehmer/innen kreativer Kommunikationsstrategien, welche die soziale Orientierung garantieren. Diese neuen, computervermittelten Diskursformen können durch die technische Realisierung und Ausstattung der Kommunikationsplattform sowie adäquate didaktische Szenarien sinnvoll unterstützt und teilweise gesteuert werden. Der eigentliche Erfolg eines virtuellen Seminars hängt jedoch von den ungesteuerten Prozessen der diskursiven Rollenkonstruktion ab.

  1. Alternative spliced CD1d transcripts in human bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Kambez Hajipouran Benam

    Full Text Available CD1d is a MHC I like molecule which presents glycolipid to natural killer T (NKT cells, a group of cells with diverse but critical immune regulatory functions in the immune system. These cells are required for optimal defence against bacterial, viral, protozoan, and fungal infections, and control of immune-pathology and autoimmune diseases. CD1d is expressed on antigen presenting cells but also found on some non-haematopoietic cells. However, it has not been observed on bronchial epithelium, a site of active host defence in the lungs. Here, we identify for the first time, CD1D mRNA variants and CD1d protein expression on human bronchial epithelial cells, describe six alternatively spliced transcripts of this gene in these cells; and show that these variants are specific to epithelial cells. These findings provide the basis for investigations into a role for CD1d in lung mucosal immunity.

  2. Employer Branding : Ett gränsöverskridande varumärkesarbete

    OpenAIRE

    Axelsson, Åsa; Granstig, Anna

    2004-01-01

    Bakgrund: Denna uppsats handlar om hur företag ska kunna attrahera framtida kompetens med en ny varumärkesstrategi. ”Employer Branding” är namnet på denna strategi och beskrivs av konsulter som ett medel för företag att via en genomtänkt varumärkesstrategi profilera företaget på kompetensmarknaden. Grunderna i en Employer Branding-strategi innefattar följande aspekter: att kunna attrahera och behålla den bästa kompetensen samt att ena företaget kring sin vision och kultur. Vi har i denna upps...

  3. Supercontinuum light sources for food analysis

    DEFF Research Database (Denmark)

    Møller, Uffe Visbech; Petersen, Christian Rosenberg; Kubat, Irnis;

    2014-01-01

    In Light & Food, a 30M DKK project funded by Innovationsfonden where DTU Fotonik has joined forces with University of Copenhagen, Aarhus University, FOSS and NKT, the vision is to develop a platform of analytical solutions to optimization of sustainable food production, both in the field...... and in the factory. These solutions will combine bright and broadband infrared light sources, so-called supercontinuum light sources,with spectroscopy, chemometrics and processing expertise and thereby contribute to increased food quality through faster and more precise analysis of grains, soils and dairy products....... One track of Light & Food will target the mid-infrared spectral region. To date, the limitations of mid-infraredlight sources, such as thermal emitters, low-power laser diodes, quantum cascade lasers and synchrotron radiation, have precluded mid-IR applications where the spatial coherence, broad...

  4. Rugby-metoden SCRUM: En ny måde at bedrive projekter på

    DEFF Research Database (Denmark)

    Pries-Heje, Lene; Pries-Heje, Jan

    2012-01-01

    En ny måde at bedrive projekter på breder sig i disse år med overraskende fart. Selv om de første tanker om ”Scrum” – hvor navnet og fremgangsmåden er inspireret af Rugby-spillet – blev tænkt for mere end 10 år siden, så er det først nu at fremgangsmåden for alvor har vundet udbredelse i Danmark....... organisatoriske kontekst. Artiklen slutter med at diskutere, hvad det er der gør, at Scrum er blevet så populær, og i dag fremstår som et reelt alternativ til klassisk plandreven projektledelse...

  5. Rugby-metoden SCRUM

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Pries-Heje, Lene

    2012-01-01

    En ny måde at bedrive projekter på breder sig i disse år med overraskende fart. Selv om de første tanker om ”Scrum” – hvor navnet og fremgangsmåden er inspireret af Rugby-spillet – blev tænkt for mere end 10 år siden, så er det først nu at fremgangsmåden for alvor har vundet udbredelse i Danmark....... organisatoriske kontekst. Artiklen slutter med at diskutere, hvad det er der gør, at Scrum er blevet så populær, og i dag fremstår som et reelt alternativ til klassisk plandreven projektledelse...

  6. Realtidsuppdatering av lokaltrafik

    OpenAIRE

    Hjälmarstedt, Mattias; Nagy, Pontus

    2014-01-01

    Denna rapport beskriver ett examensarbete utfört vid Skolan för informations- och kommunikationsteknik på Kungliga Tekniska Högskolan i Stockholm. Rapporten behandlar WebSocket som är ett nytt kommunikationsprotokoll som främst är framtaget för att förbättra prestandan inom webbkommunikationen. WebSocket är tänkt som ett substitut till HTTP inom områden som kräver låg responstid och asynkron uppdatering. WebSocket stöds idag av alla moderna webbläsare och har standardiserats av W3C (World Wid...

  7. Geschlechterdifferenzen und Geschlechtergrenzen. Über die Verflechtung von Geschlecht, Raum und Erzählung

    Directory of Open Access Journals (Sweden)

    Annika Nickenig

    2008-03-01

    Full Text Available Der vorliegende Sammelband beleuchtet aus verschiedenen Perspektiven die Verknüpfung von Geschlecht, Raum und Erzählung und löst damit seine Forderung ein, Geschlecht als Analysekategorie im interdisziplinären Forschungszusammenhang nutzbar zu machen. Die Prozesse der Konstruktion und Naturalisierung von Geschlecht werden in narratologischen und räumlichen Zusammenhängen untersucht. Mit ‚Raum‘ und ‚Erzählung‘ werden vor allem geographische und literaturwissenschaftliche Konzepte aufgerufen und miteinander verschränkt. Die Beiträge bewegen sich dabei konsequent an den Rändern der jeweiligen Disziplin und versuchen, das eigene Instrumentarium gegen den Strich zu bürsten, wodurch essentialistische Herangehensweisen vermieden werden.

  8. The NKG2D ligands RAE-1δ and RAE-1ε differ with respect to their receptor affinity, expression profiles and transcriptional regulation

    DEFF Research Database (Denmark)

    Cédile, Oriane; Popa, Natalia; Pollet-Villard, Frédéric;

    2010-01-01

    subventricular zone (SVZ) from C57BL/6 mice. RAE-1 is also expressed in vitro by neural stem/progenitor cells (NSPCs) and plays a non-immune role in cell proliferation. The C57BL/6 mouse genome contains two rae-1 genes, rae-1δ and rae-1ε encoding two different proteins. The goals of this study are first to......RAE-1 is a ligand of the activating receptor NKG2D expressed by NK cells, NKT, γδT and some CD8(+)T lymphocytes. RAE-1 is overexpressed in tumor cell lines and its expression is induced after viral infection and genotoxic stress. We have recently demonstrated that RAE-1 is expressed in the adult...

  9. Role of Interferon-γ in GVHD and GVL

    Institute of Scientific and Technical Information of China (English)

    Yong-Guang Yang; Hui Wang; Wannee Asavaroengchai; Bimalangshu R. Dey

    2005-01-01

    Interferon (IFN)-γ, a potent proinflammatory cytokine produced by multiple types of cells (e.g., activated T, NK and NKT cells), plays important and complex roles in both innate and adaptive immune responses. There may be a correlation between the IFN-γ level and GVHD severity in patients receiving allogeneic hematopoietic cell transplantation. However, such a correlation may just reflect the presence of large numbers of activated T cells,and does not necessarily imply a harmful role of IFN-γ in the pathogenesis of GVHD. There has been increasing experimental evidence that IFN-γ is not required and may even inhibit GVHD. Paradoxically, IFN-γ facilitates graft-versus-leukemic (GVL) effects. Thus, IFN-γ blockade is likely deleterious in patients after allogeneic hematopoietic cell transplantation, and not beneficial as previously suggested. Cellular & Molecular Immunology.

  10. The treatment of waste waters from pig abattoirs using Sequencing Batch Reactor technology; Depuracion de las aguas residuales generadas en los mataderos de porcino mediante tecnologia Sequencing Batch Reactor, SBR

    Energy Technology Data Exchange (ETDEWEB)

    Ferrer Guiteras, J.

    2008-07-01

    A description is provided of a pig abattoir with a provision of 200-250 l/pig, a COD load of between 10,000 and 6,000 mg/l and a BOD of between 4,000 and 2,500 mg/l and 750-500 mg-NKT/l. The pretreatment line includes a system for separating coarse and fine components, flotation and a homogenisation tank/lung. the treatment line consists of a an SBR in which the organic matter is metabolised sequentially, the nitrogen eliminated and the remainder decanted. The clarified water with 98% less organic content and 99% less nitrogen is then disposed of. The sludge is thickened and dehydrated. (Author)

  11. Varumärkeshantering : Positionera ett varumärke på spelmarknaden

    OpenAIRE

    Larsson, Jennifer; Jansson, Johan

    2011-01-01

    Problemställning: Syftet med examensarbetet var att bekräfta en position och en tilltänkt målgrupp tilluppdragsgivaren MooreGames som är en ny spelsajt på den svenska spelmarknaden. Studien är även tillför att ta fram en varumärkesplattform som i sin tur sammanfattas i en varumärkesbok. Denna bokkommer internt och externt kommunicera varumärkets värden.Teori: För att kunna få reda på hur vi på ett lyckat sätt skulle identifiera positionen hos varumärketMooreGames studerade vi teorier inom var...

  12. Marknadsläget på den nordiska elmarknaden : en analys av den nordiska prisområdesproblematiken och den svenska elmarknaden

    OpenAIRE

    Swarén, Caroline

    2001-01-01

    I Norden avreglerades elmarknaden under 1990-talet. För att skapa en effektiv marknad räcker det emellertid sällan med enbart avreglering. Ofta behövs även fler konkurrerande aktörer på marknaden. Inom vissa branscher med exempelvis höga anläggningskostnader kan det dock vara svårt för potentiella konkurrenter att etablera sig. Ett sätt kan då vara att öppna upp marknaden för internationell handel och på så sätt skapa konkurrens. Det var tänkt att den nordiska elmarknaden skulle agera som en ...

  13. Utvärdering av Studentportalen : En enkätundersökning bland studenter på Linköpings universitet

    OpenAIRE

    Dahlström, Kristin

    2009-01-01

    Studentportalen är tänkt att vara ett hjälpmedel för studenterna under deras studietid genom att tillhandahålla olika tjänster och funktioner som behövs för studierna. är kan studenterna bland annat registrera sig på kurser, anmäla sig till tentor, beställa intyg och skapa scheman. Jag gjorde en enkätundersökning bland universitetets studenter där för att utreda vad de har för åsikter om tudentportalen, e-postsystemet och, till viss del, tudentwebben. ndersökningen behandlade bland annat inlo...

  14. The Immune-Modulatory Role of Apolipoprotein E with Emphasis on Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Hong-Liang Zhang

    2010-01-01

    Full Text Available Apolipoprotein E (apoE is a 34.2 kDa glycoprotein characterized by its wide tissue distribution and multiple functions. The nonlipid-related properties of apoE include modulating inflammation and oxidation, suppressing T cell proliferation, regulating macrophage functions, and facilitating lipid antigen presentation by CD1 molecules to natural killer T (NKT cells, and so forth. Increasing studies have revealed that APOE ε allele might be associated with multiple sclerosis (MS, although evidence is still not sufficient enough. In this review, we summarized the current progress of the immunomodulatory functions of apoE, with special focus on the association of APOE ε allele with the clinical features of MS and of its animal model experimental autoimmune encephalomyelitis (EAE.

  15. Monoclonal B-cell hyperplasia and leukocyte imbalance precede development of B-cell malignancies in uracil-DNA glycosylase deficient mice

    DEFF Research Database (Denmark)

    Andersen, Sonja; Ericsson, Madelene; Dai, Hong Yan;

    2005-01-01

    monoclonal while 25% were biclonal. Monoclonality was also observed in hyperplasia, and could represent an early stage of lymphoma development. Lymphoid hyperplasia occurs very early in otherwise healthy Ung-deficient mice, observed as a significant increase of splenic B-cells. Furthermore, loss of Ung also......Ung-deficient mice have reduced class switch recombination, skewed somatic hypermutation, lymphatic hyperplasia and a 22-fold increased risk of developing B-cell lymphomas. We find that lymphomas are of follicular (FL) and diffuse large B-cell type (DLBCL). All FLs and 75% of the DLBCLs were...... causes a significant reduction of T-helper cells, and 50% of the young Ung(-/-) mice investigated have no detectable NK/NKT-cell population in their spleen. The immunological imbalance is confirmed in experiments with spleen cells where the production of the cytokines interferon gamma, interleukin 6...

  16. Dicty_cDB: Contig-U10530-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available _1( FJ205964 |pid:none) Bovine rotavirus strain KJ142 VP2 ... 34 1.7 CU466930_1507( CU466930 |pid:none) Cand...33 3.8 AJ287449_1( AJ287449 |pid:none) Human group A rotavirus partial VP... 33 3.8 (B1NKT0) RecName: Full=I...ain NRRL... 33 3.8 FJ205947_1( FJ205947 |pid:none) Bovine rotavirus strain KJ45 V...lgare NBS-LRR disease re... 32 6.5 AJ287451_1( AJ287451 |pid:none) Human group A rotavirus partial VP... 32 ...AJ287448_1( AJ287448 |pid:none) Human group A rotavirus partial VP... 32 6.5 (B1NKU2) RecName: Full=Inner ca

  17. Semantic Desktop

    Science.gov (United States)

    Sauermann, Leo; Kiesel, Malte; Schumacher, Kinga; Bernardi, Ansgar

    In diesem Beitrag wird gezeigt, wie der Arbeitsplatz der Zukunft aussehen könnte und wo das Semantic Web neue Möglichkeiten eröffnet. Dazu werden Ansätze aus dem Bereich Semantic Web, Knowledge Representation, Desktop-Anwendungen und Visualisierung vorgestellt, die es uns ermöglichen, die bestehenden Daten eines Benutzers neu zu interpretieren und zu verwenden. Dabei bringt die Kombination von Semantic Web und Desktop Computern besondere Vorteile - ein Paradigma, das unter dem Titel Semantic Desktop bekannt ist. Die beschriebenen Möglichkeiten der Applikationsintegration sind aber nicht auf den Desktop beschränkt, sondern können genauso in Web-Anwendungen Verwendung finden.

  18. Thermal properties photonic crystal fiber transducers with ferromagnetic nanoparticles

    Science.gov (United States)

    Przybysz, N.; Marć, P.; Kisielewska, A.; Jaroszewicz, L. R.

    2015-12-01

    The main aim of the research is to design new types of fiber optic transducers based on filled photonic crystal fibers for sensor applications. In our research we propose to use as a filling material nanoparticles' ferrofluids (Fe3O4 NPs). Optical properties of such transducers are studied by measurements of spectral characteristics' changes when transducers are exposed to temperature and magnetic field changes. From synthesized ferrofluid several mixtures with different NPs' concentrations were prepared. Partially filled commercially available photonic crystal fiber LMA 10 (NKT Photonics) was used to design PCF transducers. Their thermo-optic properties were tested in a temperature chamber. Taking into account magnetic properties of synthetized NPs the patch cords based on a partially filled PM 1550 PCF were measured.

  19. Radiation Recall Reaction: Two Case Studies Illustrating an Uncommon Phenomenon Secondary to Anti-Cancer Agents

    International Nuclear Information System (INIS)

    Radiation recall phenomenon is a tissue reaction that develops throughout a previously irradiated area, precipitated by the administration of certain drugs. Radiation recall is uncommon and easily neglected by physicians; hence, this phenomenon is underreported in literature. This manuscript reports two cases of radiation recall. First, a 44-year-old man with nasopharyngeal carcinoma was treated with radiotherapy in 2010 and subsequently developed multi-site bone metastases. A few days after the docetaxel-based chemotherapy, erythema and papules manifested dermatitis, as well as swallowing pain due to pharyngeal mucositis, developed on the head and neck that strictly corresponded to the previously irradiated areas. Second, a 19-year-old man with recurrent nasal NK/T cell lymphoma initially underwent radiotherapy followed by chemotherapy after five weeks. Erythema and edema appeared only at the irradiated skin. Both cases were considered chemotherapeutic agents that incurred radiation recall reactions. Clinicians should be knowledgeable of and pay attention to such rare phenomenon

  20. Growth of epitaxial films of sodium potassium tantalate and niobate on single-crystal lanthanum aluminate [100] substrates

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, George H. [University of Tennessee, Knoxville (UTK); Specht, Eliot D [ORNL; Larese, John Z [ORNL; Xue, Ziling [University of Tennessee, Knoxville (UTK); Beach, David B [ORNL

    2008-01-01

    Epitaxial films of sodium potassium tantalate (Na{sub 0.5}K{sub 0.5}TaO{sub 3}, NKT) and sodium potassium niobate (Na{sub 0.5}K{sub 0.5}NbO{sub 3}, NKN) were grown on single-crystal lanthanum aluminate (LAO) (100) (indexed as a pseudo-cubic unit cell) substrates via an all-alkoxide solution (methoxyethoxide complexes in 2-methoxyethanol) deposition route for the first time. X-ray diffraction studies indicated that the onset of crystallization in powders formed from hydrolyzed gel samples was 550 C. {sup 13}C nuclear magnetic resonance studies of solutions of methoxyethoxide complexes indicated that mixed-metal species were formed, consistent with the low crystallization temperatures observed. Thermal gravimetric analysis with simultaneous mass spectrometry showed the facile loss of the ligand (methoxyethoxide) at temperatures below 400 C. Crystalline films were obtained at temperatures as low as 650 C when annealed in air. {theta}-2{theta} x-ray diffraction patterns revealed that the films possessed c-axis alignment in that only (h00) reflections were observed. Pole-figures about the NKT or NKN (220) reflection indicated a single in-plane, cube-on-cube epitaxy. The quality of the films was estimated via {omega} (out-of-plane) and {psi} (in-plane) scans and full-widths at half-maximum (FWHMs) were found to be reasonably narrow ({approx}1{sup o}), considering the lattice mismatch between the films and the substrate.

  1. Glucagon-like peptide-1 analogue therapy for psoriasis patients with obesity and type 2 diabetes: a prospective cohort study.

    LENUS (Irish Health Repository)

    Ahern, T

    2012-06-13

    Background  Diabetes and obesity are more prevalent amongst psoriasis patients as is disturbance of the innate immune system. GLP-1 analogue therapy considerably improves weight and glycaemic control in people with type 2 diabetes and its receptor is present on innate immune cells. Objective  We aimed to determine the effect of liraglutide, a GLP-1 analogue, on psoriasis severity. Methods  Before and after 10 weeks of liraglutide therapy (1.2 mg subcutaneously daily) we determined the psoriasis area and severity index (PASI) and the dermatology life quality index (DLQI) in seven people with both psoriasis and diabetes (median age 48 years, median body mass index 48.2 kg\\/m(2) ). We also evaluated the immunomodulatory properties of liraglutide by measuring circulating lymphocyte subset numbers and monocyte cytokine production. Results  Liraglutide therapy decreased the median PASI from 4.8 to 3.0 (P = 0.03) and the median DLQI from 6.0 to 2.0 (P = 0.03). Weight and glycaemic control improved significantly. Circulating invariant natural killer T (iNKT) cells increased from 0.13% of T lymphocytes to 0.40% (P = 0.03). Liraglutide therapy also effected a non-significant 54% decrease in the proportion of circulating monocytes that produced tumour necrosis factor alpha (P = 0.07). Conclusion  GLP-1 analogue therapy improves psoriasis severity, increases circulating iNKT cell number and modulates monocyte cytokine secretion. These effects may result from improvements in weight and glycaemic control as well as from direct immune effects of GLP-1 receptor activation. Prospective controlled trials of GLP-1 therapies are warranted, across all weight groups, in psoriasis patients with and without type 2 diabetes.

  2. Infants' Peripheral Blood Lymphocyte Composition Reflects Both Maternal and Post-Natal Infection with Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Odilon Nouatin

    Full Text Available Maternal parasitoses modulate fetal immune development, manifesting as altered cellular immunological activity in cord blood that may be linked to enhanced susceptibility to infections in early life. Plasmodium falciparum typifies such infections, with distinct placental infection-related changes in cord blood exemplified by expanded populations of parasite antigen-specific regulatory T cells. Here we addressed whether such early-onset cellular immunological alterations persist through infancy. Specifically, in order to assess the potential impacts of P. falciparum infections either during pregnancy or during infancy, we quantified lymphocyte subsets in cord blood and in infants' peripheral blood during the first year of life. The principal age-related changes observed, independent of infection status, concerned decreases in the frequencies of CD4+, NKdim and NKT cells, whilst CD8+, Treg and Teff cells' frequencies increased from birth to 12 months of age. P. falciparum infections present at delivery, but not those earlier in gestation, were associated with increased frequencies of Treg and CD8+ T cells but fewer CD4+ and NKT cells during infancy, thus accentuating the observed age-related patterns. Overall, P. falciparum infections arising during infancy were associated with a reversal of the trends associated with maternal infection i.e. with more CD4+ cells, with fewer Treg and CD8+ cells. We conclude that maternal P. falciparum infection at delivery has significant and, in some cases, year-long effects on the composition of infants' peripheral blood lymphocyte populations. Those effects are superimposed on separate and independent age- as well as infant infection-related alterations that, respectively, either match or run counter to them.

  3. Innate cellular sources of interleukin-17A regulate macrophage accumulation in cigarette- smoke-induced lung inflammation in mice.

    Science.gov (United States)

    Bozinovski, Steven; Seow, Huei Jiunn; Chan, Sheau Pyng Jamie; Anthony, Desiree; McQualter, Jonathan; Hansen, Michelle; Jenkins, Brendan J; Anderson, Gary P; Vlahos, Ross

    2015-11-01

    Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). Interleukin-17A (IL-17A) is a pivotal cytokine that regulates lung immunity and inflammation. The aim of the present study was to investigate how IL-17A regulates CS-induced lung inflammation in vivo. IL-17A knockout (KO) mice and neutralization of IL-17A in wild-type (WT) mice reduced macrophage and neutrophil recruitment and chemokine (C-C motif) ligand 2 (CCL2), CCL3 and matrix metalloproteinase (MMP)-12 mRNA expression in response to acute CS exposure. IL-17A expression was increased in non-obese diabetic (NOD) severe combined immunodeficiency SCID) mice with non-functional B- and T-cells over a 4-week CS exposure period, where macrophages accumulated to the same extent as in WT mice. Gene expression analysis by QPCR (quantitative real-time PCR) of isolated immune cell subsets detected increased levels of IL-17A transcript in macrophages, neutrophils and NK/NKT cells in the lungs of CS-exposed mice. In order to further explore the relative contribution of innate immune cellular sources, intracellular IL-17A staining was performed. In the present study, we demonstrate that CS exposure primes natural killer (NK), natural killer T (NKT) and γδ T-cells to produce more IL-17A protein and CS alone increased the frequency of IL17+ γδ T-cells in the lung, whereas IL-17A protein was not detected in macrophages and neutrophils. Our data suggest that activation of innate cellular sources of IL-17A is an essential mediator of macrophage accumulation in CS-exposed lungs. Targeting non-conventional T-cell sources of IL-17A may offer an alternative strategy to reduce pathogenic macrophages in COPD. PMID:26201093

  4. Helicobacter pylori cholesteryl α-glucosides contribute to its pathogenicity and immune response by natural killer T cells.

    Directory of Open Access Journals (Sweden)

    Yuki Ito

    Full Text Available Approximately 10-15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer, while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT, which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18(-/- or wild-type mice, bacterial recovery significantly increased in Jα18(-/- compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18(-/- compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.

  5. Intrahepatic Transcriptional Signature Associated with Response to Interferon-α Treatment in the Woodchuck Model of Chronic Hepatitis B.

    Directory of Open Access Journals (Sweden)

    Simon P Fletcher

    2015-09-01

    Full Text Available Recombinant interferon-alpha (IFN-α is an approved therapy for chronic hepatitis B (CHB, but the molecular basis of treatment response remains to be determined. The woodchuck model of chronic hepatitis B virus (HBV infection displays many characteristics of human disease and has been extensively used to evaluate antiviral therapeutics. In this study, woodchucks with chronic woodchuck hepatitis virus (WHV infection were treated with recombinant woodchuck IFN-α (wIFN-α or placebo (n = 12/group for 15 weeks. Treatment with wIFN-α strongly reduced viral markers in the serum and liver in a subset of animals, with viral rebound typically being observed following cessation of treatment. To define the intrahepatic cellular and molecular characteristics of the antiviral response to wIFN-α, we characterized the transcriptional profiles of liver biopsies taken from animals (n = 8-12/group at various times during the study. Unexpectedly, this revealed that the antiviral response to treatment did not correlate with intrahepatic induction of the majority of IFN-stimulated genes (ISGs by wIFN-α. Instead, treatment response was associated with the induction of an NK/T cell signature in the liver, as well as an intrahepatic IFN-γ transcriptional response and elevation of liver injury biomarkers. Collectively, these data suggest that NK/T cell cytolytic and non-cytolytic mechanisms mediate the antiviral response to wIFN-α treatment. In summary, by studying recombinant IFN-α in a fully immunocompetent animal model of CHB, we determined that the immunomodulatory effects, but not the direct antiviral activity, of this pleiotropic cytokine are most closely correlated with treatment response. This has important implications for the rational design of new therapeutics for the treatment of CHB.

  6. 调节性T细胞与肿瘤免疫%Regulatory T cell and tumor immunity

    Institute of Scientific and Technical Information of China (English)

    张元莉; 关泉林; 祝秉东

    2012-01-01

    Regulatory T cells (Treg),a group of negative regulatory cells,have four subsets:CD4+Treg,CD8 + Treg,NKT Treg and DN Treg cells.They play an essential role in the inhibitive immune-regulation and might be the key factors of neoplasms immune escape.These mechanisms include inhibiting the effector cell function by inhibitory cytokines,killing effector cells by granzyme and perforin,competition and inhibiting IL-2,and affecting Treg differentiation and proliferation by regulating the function of CTLA-4,etc.Tumor immunotherapies targeting Treg and related immunosuppressive factors,such as remove Treg or controling the numbers and functions,enhances the immune response against tumors,which might offer a new method of tumor immunotherapy.%调节性T细胞( Treg)是一类有负调节作用的T细胞亚群,包括CD4+ Treg、CD8+ Treg、NKT Treg和DN Treg细胞等4大类,主要发挥抑制性免疫调节功能,是肿瘤免疫逃逸的重要因素.这些机制包括分泌多种免疫抑制性细胞因子、分泌颗粒酶和穿孔素杀伤效应细胞、竞争和抑制IL-2、通过T淋巴细胞毒性相关抗原(CTLA)-4影响Treg的分化和增殖等.以Treg及免疫抑制性分子作为靶点,清除Treg,控制Treg的数量和功能,增强机体对肿瘤的免疫应答,为肿瘤免疫治疗提供了新思路.

  7. 调节性T细胞与妇科恶性肿瘤免疫研究进展%Advances in the association of regulatory T cells with immune function in gynecologic cancers

    Institute of Scientific and Technical Information of China (English)

    古力米热·布然江; 古丽娜·库尔班

    2011-01-01

    调节性T细胞(regulatory T cell,Treg)是一群具有抑制其他免疫细胞功能的负调控细胞,包括CD4+Treg,CD8+Treg、自然杀伤T细胞(natural killer T cell,NKT)和双阴性Treg (double negative Treg,DN Treg )细胞等4大类.Treg细胞在妇科恶性肿瘤免疫抑制及逃逸机制中起重要作用.肿瘤可诱导生成特异性Treg细胞,CD4+ CD25+ T细胞向Treg细胞的转化可能是引起肿瘤微环境中Treg细胞数量增多的原因.本文就CD4+ CD25+Treg细胞与妇科恶性肿瘤免疫抑制及逃逸之间的关系进行综述.%Regulatory T (Treg) cells are a group of negative regulatory cells, which have a potent ability to suppress the functions of other immune cells. Treg cells have four subsets: CD4+ Treg, CD8+Treg, natural killer T cells (NKT) and double negative Treg (DN Treg) cells. Tumor specific Treg cells may limit the efficacy of anti-tumor response to gynecologic cancers. It has been identified recently that tumor cells could induce the production of tumor specific Treg cells. The accumulation and expansion of tumor specific Treg cells in tumor and the conversion of conventional CD4+ CD25+ T cells to Treg cells may contribute to the increased number of Treg cells in tumor microenvironment. Treg cells play an important role in the mechanism of immune inhibition and immune escape of gynecologic cancers.This paper briefly reviews advances in recent research on association of regulatory T cells with immune function in gynecologic cancers.

  8. Familial hemophagocytic lymphohistiocytosis: when rare diseases shed light on immune system functioning

    Directory of Open Access Journals (Sweden)

    Elena eSieni

    2014-04-01

    Full Text Available The human immune system depends on the activity of cytotoxic T lymphocytes, Natural Killer cells, and NKT cells in order to fight off a viral infection. Understanding the molecular mechanisms during this process and the role of individual proteins was greatly improved by the study of Familial Hemophagocytic Lymphohistiocytosis (FHL. Since 1999, genetic sequencing is the gold standard to classify patients into different subgroups of FHL. The diagnosis, once based on a clinical constellation of abnormalities, is now strongly supported by the results of a functional flow-cytometry screening, which directs the genetic study. A few additional congenital immune deficiencies can also cause a resembling or even identical clinical picture to FHL. As in many other rare human disorders, the collection and analysis of a relatively large number of cases in registries is crucial to draw a complete picture of the disease. The conduction of prospective therapeutic trials allows investigators to increase the awareness of the disease and to speed up the diagnostic process, but also provides important functional and genetic confirmations. Children with confirmed diagnosis may undergo hematopoietic stem cell transplantation, which is the only cure known to date. Moreover, detailed characterization of these rare patients helped to understand the function of individual proteins within the exocytic machinery of CTL, NK and NKT cells. Moreover, identification of these genotypes also provides valuable information on variant phenotypes, other than FHL, associated with biallelic and monoallelic mutations in the FHL-related genes.In this review we describe how detailed characterization of patients with genetic HLH has resulted in improvement in knowledge regarding contribution of individual proteins to the functional machinery of cytotoxic T-cells and NK cells. The review also details how identification of these genotypes has provided valuable information on variant

  9. Extranodal NK/T-Cell Lymphoma, Nasal Type, Presenting as a Breast Mass.

    Science.gov (United States)

    Rahal, Ahmad; Reddy, Pavan S; Alvares, Carmelita

    2015-01-01

    Extranodal natural killer/T-cell lymphoma, nasal type, is a rare type of non-Hodgkin cell lymphoma endemic to East Asia and parts of Central and South America. In most cases, it is driven by Epstein-Barr virus infections, with a broad range of morphologic appearances, frequent necrosis, and angioinvasion. It is designated as NK/T reflecting uncertainty in its cellular origins. These tumors usually arise in the nasal region, typically presenting with symptoms of nasal obstruction, epistaxis, and/or a destructive mass involving the nose, sinuses, or palate. The treatment of patients with extranodal NK/T-cell lymphoma, nasal type, is largely determined by the extent of disease. Localized disease is usually treated with radiation and chemotherapy. The disseminated disease requires combination chemotherapy. This report describes the case of a 30-year-old Caucasian female presenting with a left breast mass of two months duration. Excisional biopsy was done, and the pathological exam confirmed the diagnosis of extranodal NK/T-cell lymphoma, nasal type. Our patient received a systemic combination chemotherapy with steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) regimen, resulting in a complete clinical and radiological remission. On the basis of our review of the literature, extranodal NK/T non-Hodgkin cell lymphoma, nasal type, presenting as a breast mass is very rare and very uncommon in the United States. Awareness of this occurrence may be valuable as this case may be a forerunner of additional similar cases developing in the future. PMID:26824008

  10. Intrahepatic CD8+ lymphocyte trapping during tolerance induction using mushroom derived formulations: A possible role for liver in tolerance induction

    Institute of Scientific and Technical Information of China (English)

    Mony Shuvy; Tiberiu Hershcovici; Cristina Lull-Noguera; Harry Wichers; Ofer Danay; Dan Levanon; Lidya Zolotarov; Yaron Ilan

    2008-01-01

    AIM: To determine the immunomodulatory effect of Shiitake (a mushroom extract),we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis.METHODS: Four groups of mice were studied.Colitis was induced by intracolonic instillation of TNBS in groups A and B.Groups A and C were treated daily with Shiitake extract,while groups B and D received bovine serum albumin.Mice were evaluated for development of macroscopic and microscopic.The immune effects of Shiitakke were determined by FACS analysis of intra-hepatic and intrasplenic lymphocytes and IFN-γ ELISPOT assay.RESULTS: Administration of Shiitake resulted in marked alleviation of colitis,manifested by significant improvement in the macroscopic and microscopic scores,and by reduction in IFN-γ-producing colonies in group A,compared to group B mice (1.5 pfu/mL vs 3.7 pfu/mL,respectively).This beneficial effect was associated with a significant increase in the intrahepatic CD8+ lymphocyte trapping,demonstrated by an increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio.These effects were accompanied by a 17% increase in the number of intrahepatic natural killer T (NKT) cells.A similar effect was observed when Shiitake was administered to animals without disease induction.CONCLUSION: Shiitake extract affected livermediated immune regulation by altering the NKT lymphocyte distribution and increasing intrahepatic CD8+ T lymphocyte trapping,thereby leading to alleviation of immune-mediated colitis.

  11. Activation of natural killer T cells by alpha-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a coadministered protein.

    Science.gov (United States)

    Fujii, Shin-Ichiro; Shimizu, Kanako; Smith, Caroline; Bonifaz, Laura; Steinman, Ralph M

    2003-07-21

    The maturation of dendritic cells (DCs) allows these antigen-presenting cells to initiate immunity. We pursued this concept in situ by studying the adjuvant action of alpha-galactosylceramide (alphaGalCer) in mice. A single i.v. injection of glycolipid induced the full maturation of splenic DCs, beginning within 4 h. Maturation was manifest by marked increases in costimulator and major histocompatibility complex class II expression, interferon (IFN)-gamma production, and stimulation of the mixed leukocyte reaction. These changes were not induced directly by alphaGalCer but required natural killer T (NKT) cells acting independently of the MyD88 adaptor protein. To establish that DC maturation was responsible for the adjuvant role of alphaGalCer, mice were given alphaGalCer together with soluble or cell-associated ovalbumin antigen. Th1 type CD4+ and CD8+ T cell responses developed, and the mice became resistant to challenge with ovalbumin-expressing tumor. DCs from mice given ovalbumin plus adjuvant, but not the non-DCs, stimulated ovalbumin-specific proliferative responses and importantly, induced antigen-specific, IFN-gamma producing, CD4+ and CD8+ T cells upon transfer into naive animals. In the latter instance, immune priming did not require further exposure to ovalbumin, alphaGalCer, NKT, or NK cells. Therefore a single dose of alphaGalCer i.v. rapidly stimulates the full maturation of DCs in situ, and this accounts for the induction of combined Th1 CD4+ and CD8+ T cell immunity to a coadministered protein.

  12. Activation of Natural Killer T Cells by α-Galactosylceramide Rapidly Induces the Full Maturation of Dendritic Cells In Vivo and Thereby Acts as an Adjuvant for Combined CD4 and CD8 T Cell Immunity to a Coadministered Protein

    Science.gov (United States)

    Fujii, Shin-ichiro; Shimizu, Kanako; Smith, Caroline; Bonifaz, Laura; Steinman, Ralph M.

    2003-01-01

    The maturation of dendritic cells (DCs) allows these antigen-presenting cells to initiate immunity. We pursued this concept in situ by studying the adjuvant action of α-galactosylceramide (αGalCer) in mice. A single i.v. injection of glycolipid induced the full maturation of splenic DCs, beginning within 4 h. Maturation was manifest by marked increases in costimulator and major histocompatibility complex class II expression, interferon (IFN)-γ production, and stimulation of the mixed leukocyte reaction. These changes were not induced directly by αGalCer but required natural killer T (NKT) cells acting independently of the MyD88 adaptor protein. To establish that DC maturation was responsible for the adjuvant role of αGalCer, mice were given αGalCer together with soluble or cell-associated ovalbumin antigen. Th1 type CD4+ and CD8+ T cell responses developed, and the mice became resistant to challenge with ovalbumin-expressing tumor. DCs from mice given ovalbumin plus adjuvant, but not the non-DCs, stimulated ovalbumin-specific proliferative responses and importantly, induced antigen-specific, IFN-γ producing, CD4+ and CD8+ T cells upon transfer into naive animals. In the latter instance, immune priming did not require further exposure to ovalbumin, αGalCer, NKT, or NK cells. Therefore a single dose of αGalCer i.v. rapidly stimulates the full maturation of DCs in situ, and this accounts for the induction of combined Th1 CD4+ and CD8+ T cell immunity to a coadministered protein. PMID:12874260

  13. Effect of Broccoli Sprouts and Live Attenuated Influenza Virus on Peripheral Blood Natural Killer Cells: A Randomized, Double-Blind Study.

    Directory of Open Access Journals (Sweden)

    Loretta Müller

    Full Text Available Enhancing antiviral host defense responses through nutritional supplementation would be an attractive strategy in the fight against influenza. Using inoculation with live attenuated influenza virus (LAIV as an infection model, we have recently shown that ingestion of sulforaphane-containing broccoli sprout homogenates (BSH reduces markers of viral load in the nose. To investigate the systemic effects of short-term BSH supplementation in the context of LAIV-inoculation, we examined peripheral blood immune cell populations in non-smoking subjects from this study, with a particular focus on NK cells. We carried out a randomized, double-blinded, placebo-controlled study measuring the effects of BSH (N = 13 or placebo (alfalfa sprout homogenate, ASH; N = 16 on peripheral blood mononuclear cell responses to a standard nasal vaccine dose of LAIV in healthy volunteers. Blood was drawn prior to (day-1 and post (day2, day21 LAIV inoculation and analyzed for neutrophils, monocytes, macrophages, T cells, NKT cells, and NK cells. In addition, NK cells were enriched, stimulated, and assessed for surface markers, intracellular markers, and cytotoxic potential by flow cytometry. Overall, LAIV significantly reduced NKT (day2 and day21 and T cell (day2 populations. LAIV decreased NK cell CD56 and CD158b expression, while significantly increasing CD16 expression and cytotoxic potential (on day2. BSH supplementation further increased LAIV-induced granzyme B production (day2 in NK cells compared to ASH and in the BSH group granzyme B levels appeared to be negatively associated with influenza RNA levels in nasal lavage fluid cells. We conclude that nasal influenza infection may induce complex changes in peripheral blood NK cell activation, and that BSH increases virus-induced peripheral blood NK cell granzyme B production, an effect that may be important for enhanced antiviral defense responses.ClinicalTrials.gov NCT01269723.

  14. Development of solar, fuel, storage, alcoholic, and biomass technologies. (Part 1. Development of coal and geothermal energies). (Part 3. Research and development of industrial technologies); Study on practical application of amorphous solar cell (1). Study on practical application of amorphous solar cell production technology. (Study on practical application of high quality production technology). Taiyo ko hatsuden system jitsuyo ka gijutsu kaihatsu (4); Amorphous taiyo denchi no jitsuyo ka kenkyu (1). Amorphous taiyo denchi seizo gijutsu no jitsuyo ka kenkyu. (ko hinshitsu seizo gijutsu no jitsuyo ka kenkyu)

    Energy Technology Data Exchange (ETDEWEB)

    1989-09-01

    The objective of this study is the estabilishment of elemental technologies for high efficient cells by employing tandem structure of compound semiconductor and amorphous silicon/compound semiconductor, and the targets are the cell area of 1 cm{sup 2} and the efficiency of 13% or more. The research and deveopment of tandem structure were carried out using only the a-Si solar cell as the top cell. Computer simulation was adopted for the study of the output of the tandem cell to elucidate the optimum condition. Tandem cell efficiency of 10.69% was achieved by combining with a permeation type a-Si solar cell. The optimization of sintering conditions for improvement was studied to improve the characteristics of CdS/CdTe cell for use as the bottom cell. In the basic studies on CuInSe{sub 2}, monofilm formation technology and juction formation with CdS were investigated. As regards elemental study on common film formation technology, elemental studies on common film formation technology for CdS, CdTe and CIS were performed. 3 figs., 1 tab.

  15. Detection of lymphocyte subsets in peripheral blood of patients with drug eruption and its significance%药疹患者外周血淋巴细胞亚群的检测及其意义

    Institute of Scientific and Technical Information of China (English)

    谭飞; 莫小辉; 陈佳; 章楚光; 胡婷婷; 吴飞; 宋宁静; 顾军

    2014-01-01

    Objective To analyze the changes of lymphocyte subsets in peripheral blood of patients with drug eruption . Methods 18 newly diagnosed patients were served as the drug eruption group ,and were subdivided into cephalosporin group (n=9) ,penicillin group(n=5) and Chinese medicine group(n=4) according to different sensitizing drugs .20 healthy people were taken as the control group .Flow cytometry were utilized to detect the percentages and absolute counts of T lymphocytes (CD3+ ,CD3+CD4+ and CD3+CD8+ ) ,B lymphocytes ,natural killer cell(NK) and natural killer T lymphocytes(NKT) in their peripheral blood . Results Differences of percentages of T lymphocytes (CD3+ ,CD3+ CD4+ ) ,B lymphocytes ,NKT cells between the drug eruption group and the control group showed statistical significant (P0 .05) ,while that of abso-lute counts of T and B lymphocytes of patients was statistical significant between the drug eruption group and the control group (P<0 .05) .Conclusion The percentages of CD3+ ,CD3+CD4+ lymphocytes of patients with drug eruption decrease ,while those of NKT cells increase ,which may be related to the patients′immune regulation .%目的:分析药疹患者外周血淋巴细胞亚群的变化。方法将18例初诊药疹患者作为药疹组,根据致敏药物的不同将其分为头孢菌素组(n=9)、青霉素组(n=5)及中药组(n=4),将20例健康体检者作为对照组。应用流式细胞仪检测其外周血T淋巴细胞(CD3+、CD3+CD4+、CD3+CD8+)、B淋巴细胞、自然杀伤细胞(NK)和自然杀伤 T 淋巴细胞(NKT)所占百分比及其绝对计数。结果药疹组患者外周血T淋巴细胞(CD3+、CD3+ CD4+)、B淋巴细胞和N K T细胞所占百分比与对照组的差异有统计学意义(P<0.05);药疹组患者CD3+CD8+淋巴细胞所占百分比与对照组的差异无统计学意义(P>0.05),而其 T、B淋巴细胞亚群的绝对计数与对照组的

  16. Brain-derived neurotrophic factor modulates immune reaction in mice with peripheral nerve xenotransplantation

    Directory of Open Access Journals (Sweden)

    Yu X

    2016-03-01

    Full Text Available Xin Yu,1 Laijin Lu,1 Zhigang Liu,1 Teng Yang,2 Xu Gong,1 Yubo Ning,3 Yanfang Jiang4 1Department of Hand Surgery, 2Department of Orthopedics, The First Hospital of Jilin University, Changchun, 3Department of Orthopedics, Ningshi Orthopedics Hospital of Tonghua, Tonghua, 4Department of Central Laboratory, The First Hospital of Jilin University, Changchun, People’s Republic of China Background: Brain-derived neurotrophic factor (BDNF has been demonstrated to play an important role in survival, differentiation, and neurite outgrowth for many types of neurons. This study was designed to identify the role of BDNF during peripheral nerve xenotransplantation. Materials and methods: A peripheral nerve xenotransplantation from rats to mice was performed. Intracellular cytokines were stained for natural killer (NK cells, natural killer T (NKT cells, T cells, and B cells and analyzed by flow cytometry in the spleen of the recipient mouse. Serum levels of related cytokines were quantified by cytometric bead array. Results: Splenic NK cells significantly increased in the xenotransplanted mice (8.47±0.88×107 cells/mL compared to that in the control mice (4.66±0.78×107 cells/mL, P=0.0003, which significantly reduced in the presence of BDNF (4.85±0.87×107 cells/mL, P=0.0004. In contrast, splenic NKT cell number was significantly increased in the mice with xenotransplantation plus BDNF (XT + BDNF compared to that of control group or of mice receiving xenotransplantation only (XT only. Furthermore, the number of CD3+ T cells, CD3+CD4+ T cells, CD3+CD4- T cells, interferon-γ-producing CD3+CD4+ T cells, and interleukin (IL-17-producing CD3+CD4+ T cells, as well as CD3-CD19+ B cells, was significantly higher in the spleen of XT only mice compared to the control mice (P<0.05, which was significantly reduced by BDNF (P<0.05. The number of IL-4-producing CD3+CD4+ T cells and CD3+CD4+CD25+Foxp3+ T cells was significantly higher in the spleen of XT + BDNF

  17. 原发鼻腔NK/T细胞淋巴瘤影响预后的因素分析%Prognostic factors of nasal NK/T-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    马芹; 张会来; 刘霞; 周世勇; 钱正子; 翟琼莉; 付凯; 王华庆

    2013-01-01

    目的 分析鼻腔NK/T细胞淋巴瘤患者的临床特征及血液学指标,探讨影响预后的因素.方法 回顾性分析天津医科大学附属肿瘤医院80例鼻腔NK/T细胞淋巴瘤患者的临床特征及血液学指标,采用Kaplan-Meier法进行生存分析,Cox模型进行多因素分析.结果 80例患者经过治疗后,33例患者达到完全缓解,5年总生存率和无进展生存率分别为52.5%和32.5%.单因素分析显示,美国东部肿瘤协作组评分(Eastern Cooperative Oncology Group performance status,ECOGPS)、Ann Arbor分期、腔外受累、国际预后指数(international prognostic index,IPI)评分、首次治疗是否达完全缓解、治疗模式(单纯化疗与放化疗联合)、血清乳酸脱氢酶(LDH)和β2-微球蛋白和球蛋白水平、外周血白细胞计数与鼻腔NK/T细胞淋巴瘤患者的预后相关(P值均<0.05).多因素分析显示,首次治疗是否达完全缓解、LDH、腔外受累是影响鼻腔NK/T细胞淋巴瘤预后的独立危险因素(x2值分别为17.109、15.695和13.503,P值均<0.01).结论 首次治疗是否达完全缓解、LDH、腔外受累可作为鼻腔NK/T细胞淋巴瘤临床预后的参考指标.%Objective To investigate the prognostic predictors of nasal NK/T cell lymphoma.Methods Records of 80 patients with nasal NK/T cell lymphoma were analyzed retrospectively.The correlation between clinical and haematological factors and prognosis was analyzed with univariate and multivariate analysis.Results After treatment,33 of 80 patients achieved complete response,the 5-year overall survival and progression free survival were 52.5% and 32.5%,respectively.In univariate analysis,Eastern Cooperative Oncology Group performance status,Ann Arbor stage,local tumor invasion out of the nasal cavity,international prognostic index,complete response rate to the primary treatment,treatment model,lactate dehydrogenase (LDH),β2-microglobulin level,globulin and white blood cell were found to

  18. Protectin D1 reduces concanavalin A-induced liver injury by inhibiting NF-κB-mediated CX3CL1/CX3CR1 axis and NLR family, pyrin domain containing 3 inflammasome activation.

    Science.gov (United States)

    Ren, Jun; Meng, Shanshan; Yan, Bingdi; Yu, Jinyan; Liu, Jing

    2016-04-01

    Protectin D1 (PD1) is a bioactive product generated from docosahexaenoic acid, which may exert anti-inflammatory effects in various inflammatory diseases. However, the underlying molecular mechanism of its anti‑inflammatory activity on concanavalin A (Con A)-induced hepatitis remains unknown. The aim of the present study was to investigate the protective effects of PD1 against Con A‑induced liver injury and the underlying mechanisms via intravenous injection of PD1 prior to Con A administration. C57BL/6 mice were randomly divided into four experimental groups as follows: Control group, Con A group (30 mg/kg), 20 µg/kg PD1 + Con A (30 mg/kg) group and 10 µg/kg PD1 + Con A (30 mg/kg) group. PD1 pretreatment was demonstrated to significantly inhibit elevated plasma aminotransferase levels, high mobility group box 1 and liver necrosis, which were observed in Con A‑induced hepatitis. Furthermore, compared with the Con A group, PD1 pretreatment prevented the production of pro‑inflammatory cytokines, including tumor necrosis factor‑α, interferon‑γ and interleukin‑2, ‑1β and ‑6. In addition, pretreatment with PD1 markedly downregulated cluster of differentiation (CD)4+, CD8+ and natural killer T (NKT) cell infiltration in the liver. PD1 pretreatment was observed to suppress the messenger RNA and protein expression levels of NLR family, pyrin domain containing 3 and Toll‑like receptor (TLR) 4 in liver tissue samples. Further data indicated that PD1 pretreatment inhibited the activation of the nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) signaling pathway and chemokine (C‑X3‑C motif) ligand 1 (CX3CL1)/chemokine (C-X3-C motif) receptor 1 (CX3CR1) axis by preventing phosphorylation of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor, α and NF‑κB in Con A‑induced liver injury. Therefore, these results suggest that PD1 administration protects mice against Con A‑induced liver injury via

  19. Hofstedes arbejde - udbredelse og relevans; Kapitel 4: Synspunkter på anvendeligheden af Hofstede i projektarbejde; og Kapitel 5: Hofstede og videnskabsteori

    DEFF Research Database (Denmark)

    Kvistgaard, Peter; Baca, Susan; Christensen, Steen Fryba;

    1999-01-01

    Fra indledningen: Det er forfatternes ønske med det foreliggende hæfte, at det vil kunne bruges som en 'håndbog' i kritisk anvendelse af Hofstede, og det er således tiltænkt både studerende og undervisere på Fremmedsprog og Internationale Studier. Hensigten er at undersøge, hvad Hofstede faktisk...... står for i sit akademiske arbejde, hvilket vil sige, at vi vil pege på faldgruber i arbejdet med Hofstede, men vi vil også forsøge at tydeliggøre, hvilke muligheder der ligger for en positiv anvendelse af hans arbejder. Vi vil også søge at nærme os Hofstedes videnskabsteoretiske og paradigmatiske...... ståsted. Hæftet er på ingen måde ment som facitliste, men som en ramme for hvordan læseren selv kan arbejde videre med Hofstede....

  20. Der Krieg als eine besondere Form des Konflikts

    Directory of Open Access Journals (Sweden)

    Sebastian Schneider

    2011-12-01

    Full Text Available Comme le montrent les débats politiques et scientifiques actuels, la notion de guerre ne décrit pas uniquement une condition, mais a des implications normatives larges. Dans les situations de guerre, l’interdiction générale de tuer est en partie levée ou limitée. Afin d’éviter toute instrumentalisation politique et arbitraire de la notion de guerre, il faut repenser les critères de distinction entre la notion de guerre et les autres formes de conflit. Cet article se propose d’évoquer les réflexions philosophiques ainsi que politiques sur le thème de la guerre et critique le manque de réflexion sur la distinction entre la notion de guerre et les autres formes de conflits.Wie sich an aktuellen politischen und wissenschaftlichen Debatten zeigen lässt, ist der Begriff des Krieges nicht nur eine reine Zustandsbeschreibung, sondern hat auch weitreichende normative Implikationen. Im Krieg ist das ansonsten generelle Tötungsverbot partiell aufgehoben oder eingeschränkt. Um den Begriff nicht einer willkürlichen politischen Instrumentalisierung zu übergeben, muss über Kriterien zur Abgrenzung von Krieg und anderen Formen des Konflikts nachgedacht werden. Der Artikel wirft einen Blick auf die Beschäftigung der Philosophie und Politikwissenschaft mit dem Thema Krieg und kritisiert die mangelnde Abgrenzung des Krieges zu anderen Konfliktformen.

  1. Occurrence of nodular lymphocyte-predominant hodgkin lymphoma in hermansky-pudlak type 2 syndrome is associated to natural killer and natural killer T cell defects.

    Directory of Open Access Journals (Sweden)

    Luisa Lorenzi

    Full Text Available Hermansky Pudlak type 2 syndrome (HPS2 is a rare autosomal recessive primary immune deficiency caused by mutations on β3A gene (AP3B1 gene. The defect results in the impairment of the adaptor protein 3 (AP-3 complex, responsible for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism, bleeding disorders and immunodeficiency. We have studied peripheral blood and lymph node biopsies from two siblings affected by HPS2. Lymph node histology showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL in both HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an increased amount of perforin (Prf + suggesting a defect in the release of this granules-associated protein. By analyzing peripheral blood immune cells we found a significant reduction of circulating NKT cells and of CD56(brightCD16(- Natural Killer (NK cells subset. Functionally, NK cells were defective in their cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as in IFN-γ production. This defect was associated with increased baseline level of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK cells. In summary, these results suggest that a combined and profound defect of innate and adaptive effector cells might explain the susceptibility to infections and lymphoma in these HPS2 patients.

  2. Chemokines: a new dendritic cell signal for T cell activation

    Directory of Open Access Journals (Sweden)

    Christoph A Thaiss

    2011-08-01

    Full Text Available Dendritic cells (DCs are the main inducers and regulators of cytotoxic T lymphocyte (CTL responses against viruses and tumors. One checkpoint to avoid misguided CTL activation, which might damage healthy cells of the body, is the necessity for multiple activation signals, involving both antigenic as well as additional signals that reflect the presence of pathogens. DCs provide both signals when activated by ligands of pattern recognition receptors and licensed by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (classical licensing or by NKT cells (alternative licensing. Licensing regulates the DC/CTL cross-talk at multiple layers. Direct recruitment of CTLs through chemokines released by licensed DCs has recently emerged as a common theme and has a crucial impact on the efficiency of CTL responses. Here, we discuss recent advances in our understanding of DC licensing for cross-priming and implications for the temporal and spatial regulation underlying this process. Future vaccination strategies will benefit from a deeper insight into the mechanisms that govern CTL activation.

  3. T cell subpopulations.

    Science.gov (United States)

    Romagnani, Sergio

    2014-01-01

    The role of allergen-specific CD4+ effector type 2 helper (Th2) cells in the pathogenesis of allergic disorders is an established fact. Th2 cells produce interleukin (IL)-4 and IL-13, which induce immunoglobulin E production by B cells, and IL-5 that allows recruitment of eosinophils. Two main mechanisms control the Th2-mediated allergic inflammation: immune deviation (or Th1 redirection) and immune regulation. Regulatory T (Treg) cells exhibit a CD4+ phenotype and include Foxp3-positive thymic and induced Tregs, as well as Foxp3-negative IL-10-producing cells. Both immune deviation and immune regulation evoked by the maternal and newborn microbial environment probably operate in preventing allergen-specific Th2 responses. However, microbe-related protection from allergy seems to mainly depend on epigenetically controlled acetylation of the IFNG promoter of CD4+ T cells. Even Th17 and Th9 cells, as well as invariant NKT cells, have been implicated in the pathogenesis of allergic disorders, but their role is certainly more limited. Recently, innate lymphoid type 2 cells (ILC2) have been found to be able to produce high amounts of IL-5 and IL-13 in response to stimulation with IL-25 and IL-33 produced by non-immune cells. Together with Th2 cells, ILC2 may contribute to the induction and maintenance of allergic inflammation. PMID:24925396

  4. Molecular Programming of Tumor-Infiltrating CD8+ T Cells and IL15 Resistance.

    Science.gov (United States)

    Doedens, Andrew L; Rubinstein, Mark P; Gross, Emilie T; Best, J Adam; Craig, David H; Baker, Megan K; Cole, David J; Bui, Jack D; Goldrath, Ananda W

    2016-09-01

    Despite clinical potential and recent advances, durable immunotherapeutic ablation of solid tumors is not routinely achieved. IL15 expands natural killer cell (NK), natural killer T cell (NKT) and CD8(+) T-cell numbers and engages the cytotoxic program, and thus is under evaluation for potentiation of cancer immunotherapy. We found that short-term therapy with IL15 bound to soluble IL15 receptor α-Fc (IL15cx; a form of IL15 with increased half-life and activity) was ineffective in the treatment of autochthonous PyMT murine mammary tumors, despite abundant CD8(+) T-cell infiltration. Probing of this poor responsiveness revealed that IL15cx only weakly activated intratumoral CD8(+) T cells, even though cells in the lung and spleen were activated and dramatically expanded. Tumor-infiltrating CD8(+) T cells exhibited cell-extrinsic and cell-intrinsic resistance to IL15. Our data showed that in the case of persistent viral or tumor antigen, single-agent systemic IL15cx treatment primarily expanded antigen-irrelevant or extratumoral CD8(+) T cells. We identified exhaustion, tissue-resident memory, and tumor-specific molecules expressed in tumor-infiltrating CD8(+) T cells, which may allow therapeutic targeting or programming of specific subsets to evade loss of function and cytokine resistance, and, in turn, increase the efficacy of IL2/15 adjuvant cytokine therapy. Cancer Immunol Res; 4(9); 799-811. ©2016 AACR.

  5. APPLICATION OF SIX-COLOR FLOW CYTOMETRIC ANALYSIS FOR IMMUNE PROFILE MONITORING

    Directory of Open Access Journals (Sweden)

    I. V. Kudryavtsev

    2015-01-01

    Full Text Available The article deals with applications of six-color flow analysis for studying the immune state parameters by means of flow cytometry. Whole blood from healthy donors was stained with combination of monoclonal antibodies, i.e., HLA-DR-FITC, CD16+56-PE, CD4-ECD, CD19-ECD, CD8-PC5.5, CD3-PC7, CD45-APC (Beckman Coulter, USA using a “no-wash” technology. To adjust the photomultiplier (PMT voltage, we used the tubes with each of the tested monoclonal antibodies, PMT voltage was considered optimal when the negative population was located in the middle of the first decade at the logarithmic scale. The compensatory adjustment was performed in automatic mode, using Navios software (Beckman Coulter, USA. We discuss an optimal gating strategy in order to assess the populations of interest: total T cells (CD3+CD19-, T helper cells (CD3+CD4+, cytotoxic T lymphocytes (CD3+CD8+, B cells (CD3-CD19+, NK cells (CD3-CD16+CD56+, NKT cells (CD3+CD16+CD56+, activated T lymphocytes (CD3+HLA-DR+. 

  6. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis.

    Directory of Open Access Journals (Sweden)

    Nina Fransén-Pettersson

    Full Text Available Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders.

  7. Regulation and antimetastatic functions of liver-associated natural killer cells.

    Science.gov (United States)

    Wiltrout, R H

    2000-04-01

    The liver is a complex organ composed of hepatic parenchymal cells and a variety of non-parenchymal cells that consist of endothelial cells, Kupffer cells, and several subsets of resident lymphocytes, including natural killer (NK), T, and NK1.1+/CD3+ (NK/T) cells. The regulation of these various lymphoid subpopulations and their relative contributions to antiviral, antitumor and pathogenic inflammatory responses in the liver remain topics of much interest. Studies from our laboratory have shown that various immune stimulants and cytokines can augment liver-associated NK activity at least partially through the mobilization of NK cells from the bone marrow to the liver. The mobilization process can be dependent on the induction of interferon (IFN)-gamma and/or tumor necrosis factor-alpha and on very late activation antigen-4/vascular cell adhesion molecule-1 interaction. The induction of IFN-gamma by cytokines such as interleukin (IL)-12 also rapidly triggers the induction of chemokine genes in parenchymal cells that may contribute to the localization of NK and T cells. Both IL-2 and IL-12 trigger changes in the number and functions of liver-associated leukocyte subsets, and induce antimetastatic effects that are likely mediated through several direct and indirect mechanisms. The overall goal of these studies is to understand the interactions and functions of liver-associated NK1.1+ cells in the context of innate and adaptive immune responses to neoplasia.

  8. Ontogeny of innate T lymphocytes - some innate lymphocytes are more innate then others

    Directory of Open Access Journals (Sweden)

    David eVermijlen

    2014-10-01

    Full Text Available Innate lymphocytes have recently received a lot of attention. However, there are different ideas about the definition of what is innate in lymphocytes. Lymphocytes without V(DJ-rearranged antigen receptors are now termed innate lymphoid cells (ILCs and include cells formerly known as NK cells. Also, lymphocytes that are innate should be able to recognize microbial or stress-induced patterns and react rapidly without prior sensitization, as opposed to adaptive immune responses. Formally, genuine innate lymphocytes would be present before or at birth. Here we review the ontogeny of human and mouse innate T lymphocyte populations. We focus on γδ T cells, which are prototype lymphocytes that often use their V(DJ rearrangement machinery to generate genetically encoded predetermined recombinations of antigen receptors. We make parallels between the development of γδ T cells with that of innate aβ T cells (invariant (iNKT and mucosa-associated invariant T (MAIT cells and compare this with the ontogeny of innate B cells and innate lymphoid cells (ILCs, including NK cells. We conclude that some subsets are more innate than others, i.e. innate lymphocytes that are made primarily early in utero during gestation while others are made after birth. In practice, a ranking of innateness by ontogeny has implications for the reconstitution of innate lymphocyte subsets after hematopoietic stem cell transplantation (HSCT.

  9. Paneth cell extrusion and release of antimicrobial products is directly controlled by immune cell-derived IFN-γ.

    Science.gov (United States)

    Farin, Henner F; Karthaus, Wouter R; Kujala, Pekka; Rakhshandehroo, Maryam; Schwank, Gerald; Vries, Robert G J; Kalkhoven, Eric; Nieuwenhuis, Edward E S; Clevers, Hans

    2014-06-30

    Paneth cells (PCs) are terminally differentiated, highly specialized secretory cells located at the base of the crypts of Lieberkühn in the small intestine. Besides their antimicrobial function, PCs serve as a component of the intestinal stem cell niche. By secreting granules containing bactericidal proteins like defensins/cryptdins and lysozyme, PCs regulate the microbiome of the gut. Here we study the control of PC degranulation in primary epithelial organoids in culture. We show that PC degranulation does not directly occur upon stimulation with microbial antigens or bacteria. In contrast, the pro-inflammatory cytokine Interferon gamma (IFN-γ) induces rapid and complete loss of granules. Using live cell imaging, we show that degranulation is coupled to luminal extrusion and death of PCs. Transfer of supernatants from in vitro stimulated iNKT cells recapitulates degranulation in an IFN-γ-dependent manner. Furthermore, endogenous IFN-γ secretion induced by anti-CD3 antibody injection causes Paneth loss and release of goblet cell mucus. The identification of IFN-γ as a trigger for degranulation and extrusion of PCs establishes a novel effector mechanism by which immune responses may regulate epithelial status and the gut microbiome.

  10. Particle Acceleration during Magnetic Reconnection in a Low-beta Pair Plasma

    CERN Document Server

    Guo, Fan; Daughton, William; Li, Xiaocan; Liu, Yi-Hsin

    2016-01-01

    Plasma energization through magnetic reconnection in the magnetically-dominated regime featured by low plasma beta ($\\beta = 8 \\pi nkT_0/B^2 \\ll 1$) and/or high magnetization ($\\sigma = B^2/(4 \\pi nmc^2) \\gg 1$) is important in a series of astrophysical systems such as solar flares, pulsar wind nebula, and relativistic jets from black holes, etc. In this paper, we review the recent progress on kinetic simulations of this process and further discuss plasma dynamics and particle acceleration in a low-$\\beta$ reconnection layer that consists of electron-positron pairs. We also examine the effect of different initial thermal temperatures on the resulting particle energy spectra. While earlier papers have concluded that the spectral index is smaller for higher $\\sigma$, our simulations show that the spectral index approaches $p=1$ for sufficiently low plasma $\\beta$, even if $\\sigma \\sim 1$. Since this predicted spectral index in the idealized limit is harder than most observations, it is important to consider eff...

  11. Mobilgenerationens Kennedymord?

    DEFF Research Database (Denmark)

    Hansen, Tia

    timer efter angrebet på World Trade Center og Pentagon. Med disse beskrives nyhedens spredningshastighed og kommunikationskanaler, de unges umiddelbare reaktioner og eksempler på, hvad de allerede da vidste om angrebet selv og formodede om dets videre kontekst. Der gives også en skitse af danske mediers...... erindringerne efter ni måneder, og korrekt erindring af egen tilegnelse hos seks ud af ti, men sikkerhed på at huske korrekt hos flere; og den store livagtighed af og tiltro til erindringerne vises at samvariere med vurderinger d. 12. september 2001 af niveauet for, hvor meget man havde tænkt på og talt om...... angrebet de første 24 timer. Resultaterne vurderes at være i bedre overensstemmelse med teorien om blitzerindring som dannet af almindelige hukommelsesmekanismer, der virker over tid, end med teorien om en særmekanisme, der virker i øjeblikket, og der argumenteres for, at dette er kompatibelt med...

  12. Construction and Functional Characterization of a Fusion Protein Interleukin-21/Immunoglobulin for Long-Term In Vivo Biodisponibility.

    Science.gov (United States)

    Gassen, Rodrigo Benedetti; Romão, Pedro Roosevelt T; Freitas, Deise Nascimentode; Rodrigues Junior, Luiz Carlos

    2016-03-01

    Interleukin (IL)-21 has been intensively studied for use in therapy of autoimmune diseases, cancers, and chronic viruses due to its immunomodulatory properties, especially on CD4(+) and CD8(+) T cells and natural killer (NK) cells. The objective of this study was to produce an optimized form of IL-21 with improved stability. Plasmids encoding the murine IL-21 alone (pIL-21) or IL-21 genetically fused to portions from mouse IgG3 (pIL-21/Ig) were constructed, and the efficiency of expression, protein kinetics, biodisponibility, and function were analyzed. The genetic constructions of pIL-21 and pIL-21/Ig were transfected into HEK 293 cells, and significant levels of functional IL-21 were obtained. The amino acid of murine IL-21 and IgG3 cloned showed 100% identity with correspondent published sequences. At 24 h of incubation, increased levels of IL-21 were detected in the supernatants of pIL-21. At 72 h of culture, the levels of IL-21 in the supernatant of cells transfected with pIL-21/Ig were significantly higher than those secreted by pIL-21-transfected cells. Furthermore, the data showed that our chimeric IL-21/Ig present improved systemic disponibility in BALB/c mice and conserved the intrinsic ability to increase the frequency of CD4(+) T cells, NKT cells, and CD8(+) T cells. PMID:26720885

  13. Natural Killer Cells and Liver Transplantation: Orchestrators of Rejection or Tolerance?

    Science.gov (United States)

    Harmon, C; Sanchez-Fueyo, A; O'Farrelly, C; Houlihan, D D

    2016-03-01

    Natural killer (NK) cells are highly heterogeneous innate lymphocytes with a diverse repertoire of phenotypes and functions. Their role in organ transplantation has been poorly defined due to conflicting clinical and experimental data. There is evidence that NK cells can contribute to graft rejection and also to tolerance induction. In most solid organ transplantation settings, the role of NK cells is only considered from the perspective of the recipient immune system. In contrast to other organs, the liver contains major resident populations of immune cells, particularly enriched with innate lymphocytes such as NK cells, NKT cells, and gamma-delta T cells. Liver transplantation therefore results in a unique meeting of donor and recipient immune systems. The unusual immune repertoire and tolerogenic environment of the liver may explain why this potentially inflammatory "meeting" often results in attenuated immune responses and reduced requirement for immunosuppression. Recent trials of immunosuppression withdrawal in liver transplant patients have identified NK cell features as possible predictors of tolerance. Here we propose that hepatic NK cells play a key role in the induction of tolerance post-liver transplant and examine potential mechanisms by which these cells influence liver transplant outcome.

  14. Salivary gland NK cells are phenotypically and functionally unique.

    Directory of Open Access Journals (Sweden)

    Marlowe S Tessmer

    Full Text Available Natural killer (NK cells and CD8(+ T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV. However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer NK-like cells and are not thymic derived. During the course of murine cytomegalovirus (MCMV infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited capacity to produce IFN-γ and degranulate. Salivary gland NK cell effector functions are not regulated by iNKT or T(reg cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that viral persistence and latency in the salivary glands may be due in part to the presence of unfit NK cells and the lack of recruitment of peripheral NK cells.

  15. Salivary gland NK cells are phenotypically and functionally unique.

    Science.gov (United States)

    Tessmer, Marlowe S; Reilly, Emma C; Brossay, Laurent

    2011-01-13

    Natural killer (NK) cells and CD8(+) T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV). However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population that resides in the salivary gland, uncommon to any described to date, expressing both mature and immature NK cell markers. Using RORγt reporter mice and nude mice, we also show that the salivary gland NK cells are not lymphoid tissue inducer NK-like cells and are not thymic derived. During the course of murine cytomegalovirus (MCMV) infection, we found that salivary gland NK cells detect the infection and acquire activation markers, but have limited capacity to produce IFN-γ and degranulate. Salivary gland NK cell effector functions are not regulated by iNKT or T(reg) cells, which are mostly absent in the salivary gland. Additionally, we demonstrate that peripheral NK cells are not recruited to this organ even after the systemic infection has been controlled. Altogether, these results indicate that viral persistence and latency in the salivary glands may be due in part to the presence of unfit NK cells and the lack of recruitment of peripheral NK cells.

  16. Characterization of CRTAM gene promoter: AP-1 transcription factor control its expression in human T CD8 lymphocytes.

    Science.gov (United States)

    Valle-Rios, Ricardo; Patiño-Lopez, Genaro; Medina-Contreras, Oscar; Canche-Pool, Elsy; Recillas-Targa, Felix; Lopez-Bayghen, Esther; Zlotnik, Albert; Ortiz-Navarrete, Vianney

    2009-10-01

    Class-I MHC-restricted T-cell associated molecule (CRTAM) is a member of the Nectin-like adhesion molecule family. It is rapidly induced in NK, NKT and CD8(+) T cells. Interaction with its ligand Nectin-like 2 results in increased secretion of IFN-gamma by activated CD8(+) T lymphocytes. Through sequential bioinformatic analyses of the upstream region of the human CRTAM gene, we detected cis-elements potentially important for CRTAM gene transcription. Analyzing 2kb upstream from the ATG translation codon by mutation analysis in conjunction with luciferase reporter assays, electrophoretic mobility shify assay (EMSA) and supershift assays, we identified an AP-1 binding site, located at 1.4kb from the ATG translation codon of CRTAM gene as an essential element for CRTAM expression in activated but not resting human CD8(+) T cells. CRTAM expression was reduced in activated CD8(+) T cells treated with the JNK inhibitor SP600125, indicating that CRTAM expression is driven by the JNK-AP-1 signaling pathway. This study represents the first CRTAM gene promoter analysis in human T cells and indicates that AP-1 is a positive transcriptional regulator of this gene, a likely important finding because CRTAM has recently been shown to play a role in IFN-gamma and IL-17 production and T cell proliferation.

  17. Curcumin ameliorates experimental autoimmune myasthenia gravis by diverse immune cells.

    Science.gov (United States)

    Wang, Shan; Li, Heng; Zhang, Min; Yue, Long-Tao; Wang, Cong-Cong; Zhang, Peng; Liu, Ying; Duan, Rui-Sheng

    2016-07-28

    Curcumin is a traditional Asian medicine with diverse immunomodulatory properties used therapeutically in the treatment of many autoimmune diseases. However, the effects of curcumin on myasthenia gravis (MG) remain undefined. Here we investigated the effects and potential mechanisms of curcumin in experimental autoimmune myasthenia gravis (EAMG). Our results demonstrated that curcumin ameliorated the clinical scores of EAMG, suppressed the expression of T cell co-stimulatory molecules (CD80 and CD86) and MHC class II, down-regulated the levels of pro-inflammatory cytokines (IL-17, IFN-γ and TNF-α) and up-regulated the levels of the anti-inflammatory cytokine IL-10, shifted the balance from Th1/Th17 toward Th2/Treg, and increased the numbers of NKR-P1(+) cells (natural killer cell receptor protein 1 positive cells, including NK and NKT cells). Moreover, the administration of curcumin promoted the differentiation of B cells into a subset of B10 cells, increased the anti-R97-166 peptide IgG1 levels and decreased the relative affinity indexes of anti-R97-116 peptide IgG. In summary, curcumin effectively ameliorate EAMG, indicating that curcumin may be a potential candidate therapeutic agent for MG. PMID:27181511

  18. ISCOMATRIX Adjuvant Combines Immune Activation with Antigen Delivery to Dendritic Cells In Vivo Leading to Effective Cross-Priming of CD8+ T Cells

    Science.gov (United States)

    Duewell, Peter; Kisser, Ulrich; Heckelsmiller, Klaus; Hoves, Sabine; Stoitzner, Patrizia; Koernig, Sandra; Morelli, Adriana B.; Clausen, Björn E.; Dauer, Marc; Eigler, Andreas; Anz, David; Bourquin, Carole; Maraskovsky, Eugene; Endres, Stefan; Schnurr, Max

    2014-01-01

    Cancer vaccines aim to induce CTL responses against tumors. Challenges for vaccine design are targeting Ag to dendritic cells (DCs) in vivo, facilitating cross-presentation, and conditioning the microenvironment for Th1 type immune responses. In this study, we report that ISCOM vaccines, which consist of ISCOMATRIX adjuvant and protein Ag, meet these challenges. Subcutaneous injection of an ISCOM vaccine in mice led to a substantial influx and activation of innate and adaptive immune effector cells in vaccine site-draining lymph nodes (VDLNs) as well as IFN-γ production by NK and NKT cells. Moreover, an ISCOM vaccine containing the model Ag OVA (OVA/ISCOM vaccine) was efficiently taken up by CD8α+ DCs in VDLNs and induced their maturation and IL-12 production. Adoptive transfer of transgenic OT-I T cells revealed highly efficient cross-presentation of the OVA/ISCOM vaccine in vivo, whereas cross-presentation of soluble OVA was poor even at a 100-fold higher concentration. Cross-presenting activity was restricted to CD8α+ DCs in VDLNs, whereas Langerin+ DCs and CD8α− DCs were dispensable. Remarkably, compared with other adjuvant systems, the OVA/ISCOM vaccine induced a high frequency of OVA-specific CTLs capable of tumor cell killing in different tumor models. Thus, ISCOM vaccines combine potent immune activation with Ag delivery to CD8α+ DCs in vivo for efficient induction of CTL responses. PMID:21613613

  19. A Multifactorial Mechanism in the Superior Antimalarial Activity of α-C-GalCer

    Directory of Open Access Journals (Sweden)

    John Schmieg

    2010-01-01

    Full Text Available We have previously shown that the C-glycoside analog of α-galactosylceramide (α-GalCer, α-C-GalCer, displays a superior inhibitory activity against the liver stages of the rodent malaria parasite Plasmodium yoelii than its parental glycolipid, α-GalCer. In this study, we demonstrate that NK cells, as well as IL-12, are a key contributor for the superior activity displayed by α-C-GalCer. Surprisingly, the diminished production of Th2 cytokines, including IL-4, by α-C-GalCer has no affect on its superior therapeutic activity relative to α-GalCer. Finally, we show that the in vivo administration of α-C-GalCer induces prolonged maturation of dendritic cells (DCs, as well as an enhanced proliferative response of mouse invariant Vα14 (Vα14i NKT cells, both of which may also contribute to some degree to the superior activity of α-C-GalCer in vivo.

  20. Geschlechterdifferenzen und Geschlechtergrenzen. Über die Verflechtung von Geschlecht, Raum und Erzählung Gender Differences and Gender Limits. On the Link between Gender, Space, and Narrative

    Directory of Open Access Journals (Sweden)

    Annika Nickenig

    2008-03-01

    Full Text Available Der vorliegende Sammelband beleuchtet aus verschiedenen Perspektiven die Verknüpfung von Geschlecht, Raum und Erzählung und löst damit seine Forderung ein, Geschlecht als Analysekategorie im interdisziplinären Forschungszusammenhang nutzbar zu machen. Die Prozesse der Konstruktion und Naturalisierung von Geschlecht werden in narratologischen und räumlichen Zusammenhängen untersucht. Mit ‚Raum‘ und ‚Erzählung‘ werden vor allem geographische und literaturwissenschaftliche Konzepte aufgerufen und miteinander verschränkt. Die Beiträge bewegen sich dabei konsequent an den Rändern der jeweiligen Disziplin und versuchen, das eigene Instrumentarium gegen den Strich zu bürsten, wodurch essentialistische Herangehensweisen vermieden werden.The collected volume at hand illuminates the connection between gender, space, and narrative from different perspectives and thus honors its intention of transforming gender into a useful category for analysis within interdisciplinary research. It examines the processes of construction and naturalization of gender in narratological and spatial contexts. In particular, the terms ’space’ and ‘narrative’ conjure up and entangle geographical and literary concepts. The contributions thus continuously move along the borders of the respective disciplines and attempt to go against the grain of their own analytical tools in order to avoid essentialist approaches.

  1. Die grünende IT - Wie die Computerindustrie das Energiesparen neu erfand

    Science.gov (United States)

    von Greiner, Wilhelm

    Die IT-Branche hat ihr grünes Gewissen entdeckt. In der jetzigen Verbreitung und Intensität ist dieses Phänomen noch recht neu - lange Zeit schien die Informationstechnik in puncto Umweltverträglichkeit und Energieverbrauch eine "weiße Weste" zu haben. Schließlich läuft ein PC mit Strom und nicht mit - sagen wir mal - einem Dieselmotor: Beim Booten eines Computers schießt nicht erst eine dunkelgraue Rauchwolke aus dem Auspuff, die Lärmerzeugung beschränkt sich auf das Surren des Lüfters, zum Tanken fahren muss man mit ihm auch nicht, und die Produktion der Komponenten erfolgt… ja, wo eigentlich? Irgendwo in der "dritten Welt", in Fernost oder in Mexiko. So sind die umweltschädlichen Aspekte der Produktion von Leiterplatten und sonstigen Bauteilen aus den Augen, aus dem Sinn und bestenfalls sporadisch Gegenstand eines kritischen Greenpeace-Berichts1, der im Überangebot der Medienlandschaft untergeht.

  2. Flow Cytometric Analysis of T, B, and NK Cells Antigens in Patients with Mycosis Fungoides.

    Science.gov (United States)

    Yazıcı, Serkan; Bülbül Başkan, Emel; Budak, Ferah; Oral, Barbaros; Adim, Şaduman Balaban; Ceylan Kalin, Zübeyde; Özkaya, Güven; Aydoğan, Kenan; Saricaoğlu, Hayriye; Tunali, Şükran

    2015-01-01

    We retrospectively analyzed the clinicopathological correlation and prognostic value of cell surface antigens expressed by peripheral blood mononuclear cells in patients with mycosis fungoides (MF). 121 consecutive MF patients were included in this study. All patients had peripheral blood flow cytometry as part of their first visit. TNMB and histopathological staging of the cases were retrospectively performed in accordance with International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) criteria at the time of flow cytometry sampling. To determine prognostic value of cell surface antigens, cases were divided into two groups as stable and progressive disease. 17 flow cytometric analyses of 17 parapsoriasis (PP) and 11 analyses of 11 benign erythrodermic patients were included as control groups. Fluorescent labeled monoclonal antibodies were used to detect cell surface antigens: T cells (CD3(+), CD4(+), CD8(+), TCRαβ(+), TCRγδ(+), CD7(+), CD4(+)CD7(+), CD4(+)CD7(-), and CD71(+)), B cells (HLA-DR(+), CD19(+), and HLA-DR(+)CD19(+)), NKT cells (CD3(+)CD16(+)CD56(+)), and NK cells (CD3(-)CD16(+)CD56(+)). The mean value of all cell surface antigens was not statistically significant between parapsoriasis and MF groups. Along with an increase in cases of MF stage statistically significant difference was found between the mean values of cell surface antigens. Flow cytometric analysis of peripheral blood cell surface antigens in patients with mycosis fungoides may contribute to predicting disease stage and progression. PMID:26788525

  3. Immunological profile of HTLV-1-infected patients associated with infectious or autoimmune dermatological disorders.

    Directory of Open Access Journals (Sweden)

    Jordana Grazziela Alves Coelho-dos-Reis

    Full Text Available In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4(+HLA-DR(+, CD8(+ T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.

  4. MicroRNAs: New regulators of IL-22.

    Science.gov (United States)

    Lu, Zhou; Liu, Ronghua; Huang, Enyu; Chu, Yiwei

    2016-01-01

    Interleukin-22 (IL-22) is a cytokine that belongs to the IL-10 family of interleukins. It can be produced by T helper 22 (Th22) cells, T helper 1 (Th1) cells, T helper 17 (Th17) cells, natural killer 22 (NK22) cells, natural killer T (NKT) cells, innate lymphoid cells (ILCs), and γδ T cells. IL-22 acts via binding to a heterodimeric transmembrane receptor complex that consists of IL-22R1 and IL-10R2 and mainly contributes to the tissue repair and host defense. Transcription factors such as retinoid orphan receptor γt (RORγt) and signal transducer and activator of transcription 3 (STAT3), have been reported to play important roles in regulation of IL-22 expression. Recently, it has been demonstrated in several studies that microRNAs (miRNAs) potently regulate expression of interleukins, including production of IL-22. Here, we review current knowledge about regulators of IL-22 expression with a particular emphasis on the role of miRNAs. PMID:27221197

  5. LKB1 mediates the development of conventional and innate T cells via AMP-dependent kinase autonomous pathways.

    Directory of Open Access Journals (Sweden)

    Marouan Zarrouk

    Full Text Available The present study has examined the role of the serine/threonine kinase LKB1 in the survival and differentiation of CD4/8 double positive thymocytes. LKB1-null DPs can respond to signals from the mature α/β T-cell-antigen receptor and initiate positive selection. However, in the absence of LKB1, thymocytes fail to mature to conventional single positive cells causing severe lymphopenia in the peripheral lymphoid tissues. LKB1 thus appears to be dispensable for positive selection but important for the maturation of positively selected thymocytes. LKB1 also strikingly prevented the development of invariant Vα14 NKT cells and innate TCR αβ gut lymphocytes. Previous studies with gain of function mutants have suggested that the role of LKB1 in T cell development is mediated by its substrate the AMP-activated protein kinase (AMPK. The present study now analyses the impact of AMPK deletion in DP thymocytes and shows that the role of LKB1 during the development of both conventional and innate T cells is mediated by AMPK-independent pathways.

  6. Radioaktive Biomaterialien

    Science.gov (United States)

    Assmann, Walter

    In der Strahlentherapie von Tumorgewebe (Radioonkologie) nutzt man die zellschädigende Wirkung verschiedener Strahlenarten zur gezielten Abtötung der Tumorzellen. Um bei der perkutanen Bestrahlung die Strahlenschäden im gesunden Gewebe in Grenzen zu halten, wird der Tumor aus verschiedenen Richtungen mit gut fokussiertem Strahl behandelt. Moderne Bestrahlungsanlagen sind durch Steuerung über leistungsfähige Rechner in der Lage, ein millimetergenaues Bestrahlungsprogramm abzufahren, das individuell auf den jeweiligen Tumor abgestimmt ist. Ein ganz anderer Weg, das umgebende gesunde Gewebe zu schonen, wird in der sog. Brachytherapie beschritten. Hier wird ein kurzreichweitiger, radioaktiver Strahler entweder direkt in das Tumorgewebe (interstitiell) oder in grosser Nähe (intrakavitär) permanent oder nur für eine bestimmte Zeitdauer eingebracht. Ein Beispiel ist die Behandlung des Prostatakarzinoms durch die Implantation von dünnwandigen metallischen Hülsen (seeds) von nur wenigen Millimetern Länge und knapp einem Millimeter Durchmesser, die minimalinvasiv mittels feiner Kanülen in die Prostata eingebracht werden. Sie enthalten ein künstliches Radionuklid mit typisch einigen Wochen Halbwertszeit, dessen therapeutisch wirksame Strahlungsdosis sich auf wenige Millimeter des umgebenden Gewebes beschränkt. Wesentlich für den Erfolg einer Strahlentherapie mit derartig kurzreichweitigen Strahlern ist eine Lagekontrolle mit entsprechend hoher räumlicher Auflösung.

  7. Echt und modern? Diskurse über Männlichkeit

    Directory of Open Access Journals (Sweden)

    Florian Kahofer

    2014-09-01

    Full Text Available Der vorliegende Artikel befasst sich mit Repräsentationen von Männlichkeit im österreichischen Lifestyle-Magazin für Männer Wiener. Durch eine korpusbasierte Diskursanalyse wird ein umfassendes Korpus aller Ausgaben des Wieners von Anfang 2002 bis Ende 2012 untersucht. Auf theoretischer Ebene wird dabei eine Verbindung von Kritischer Männlichkeitsforschung (KMF und Feministisch Kritischer Diskursanalyse (FCDA unternommen. Es werden aktuelle Veröffentlichungen zu Kritischer Diskursanalyse und Männlichkeit vorgestellt und diskutiert. Durch den Einsatz einer Konkordanzsoftware werden Konkordanzen des Nomens MANN analysiert. Diese werden allerdings insofern eingeschränkt betrachtet, als nur Nominationen in der Form der häufigsten Adjektiv-Konstruktionen untersucht werden. Die Ergebnisse zeigen, dass neben den Diskursen über Krise und Neue Männlichkeit Themen wie Alter, Körper oder Beziehung auftauchen. Männlichkeit wird als ambivalent und vielfältig dargestellt. Deutungskämpfe um Männlichkeit lassen sich ausmachen.

  8. Visit of Danish firms at CERN

    CERN Multimedia

    GS Department

    2012-01-01

    30 – 31 JANUARY 2012 09h00 to 17h00 Monday 30 January 09h00 to 17h00 Tuesday 31 January Individual interviews will take place in technicians’ offices. The firms will contact relevant users/technicians but any user wishing to make contact with a particular firm is welcome to use the contact details which are available from each secretariat of department or from the GS Department web pages at the following URL http://gs-dep.web.cern.ch/en/content/Industrial-Exhibitions List of Companies: Axcon APS BB Electronics A/S B.Rustfrit Stal A/S CIM Industrial Systems A/S Danfysik A/S Develco A/S Eletronic A/S GPV Group Innoware A/S JLI Vision A/S NECAS A/S NKT Cables A/S Noliac A/S Röttger’s Vaerktoj A/S   For further information please contact Claudia Bruggmann Furlan  GS-IS-LS 73312 or Caroline Laignel GS-DI 73722.

  9. Danish firms visit CERN

    CERN Multimedia

    FP Department

    2011-01-01

    30 – 31 JANUARY 2012 09:00 to 17:00 Monday 30 January 09:00 to 17:00 Tuesday 31 January Individual interviews will take place in technicians’ offices. The firms will contact relevant users/technicians but any user wishing to make contact with a particular firm is welcome to use the contact details available from the secretariat of their department or from the GS Department web page. List of Companies: · Axcon APS · BB Electronics A/S · B.Rustfrit Stal A/S · CIM Industrial Systems A/S · Danfysik A/S · Develco A/S · Eletronic A/S · GPV Group · Innoware A/S · JLI Vision A/S · NECAS A/S· NKT Cables A/S · Noliac A/S · Prodan A/S · Röttger’s Vaerktoj A/S · Vengcon APS For further information please contact Claudia Bruggmann Furlan  GS-IS-LS 73312 or Caroline Laignel GS-DI 73722.

  10. Molecular Mechanism and Treatment of Viral Hepatitis-Related Liver Fibrosis

    Directory of Open Access Journals (Sweden)

    Tung-Hung Su

    2014-06-01

    Full Text Available Hepatic fibrosis is a wound-healing response to various chronic stimuli, including viral hepatitis B or C infection. Activated myofibroblasts, predominantly derived from the hepatic stellate cells (HSCs, regulate the balance between matrix metalloproteinases and their tissue inhibitors to maintain extracellular matrix homeostasis. Transforming growth factor-β and platelet-derived growth factor are classic profibrogenic signals that activate HSC proliferation. In addition, proinflammatory cytokines and chemokines coordinate macrophages, T cells, NK/NKT cells, and liver sinusoidal endothelial cells in complex fibrogenic and regression processes. In addition, fibrogenesis involves angiogenesis, metabolic reprogramming, autophagy, microRNA, and epigenetic regulations. Hepatic inflammation is the driving force behind liver fibrosis; however, host single nucleotide polymorphisms and viral factors, including the genotype, viral load, viral mutation, and viral proteins, have been associated with fibrosis progression. Eliminating the underlying etiology is the most crucial antifibrotic therapy. Growing evidence has indicated that persistent viral suppression with antiviral therapy can result in fibrosis regression, reduced liver disease progression, decreased hepatocellular carcinoma, and improved chances of survival. Preclinical studies and clinical trials are currently examining several investigational agents that target key fibrogenic pathways; the results are promising and shed light on this debilitating illness.

  11. Fra kold krig til internationalt engagement

    DEFF Research Database (Denmark)

    Nørby, Søren; Muusfeldt, Henrik; Hansen, Bent;

    Historien om de tre korvetter Niels Juel, Olfert Fischer og Peter Tordenskiold er det danske søværns historie fra den Kolde Krig og frem til dagens globale indsats. Oprindeligt tiltænkt en rolle som lillebrødre til søværnets fregatter kom korvetterne efter fregatternes udfasning i 1988 til...... at optræde som søværnets og Danmarks repræsentant i NATO og på internationale operationer langt fra de danske farvande, som de oprindeligt var bygget til at beskytte. Som noget ganske enestående i søværnets nyere historie kom korvetterne også i krig. To gange var Olfert Fischer i den Persiske Golf...... for at forsvare danske interesser – med våbenmagt om nødvendigt. Korvettens våben blev aldrig affyret i vrede, men man var klar til at være klar og repræsenterede på denne måde på fornemste vis søværnets traditioner. Denne bog beskriver de tre skibes historie fra tilblivelsen under den Kolde Krig til deres...

  12. Ökonomie der Bandbreite: Evolutionär-ökonomische und kulturanthropologische Überlegungen zu Schnittstellen in Mensch-Maschine-Komplexen

    Directory of Open Access Journals (Sweden)

    Manuel Wäckerle

    2012-09-01

    Full Text Available In diesem Artikel diskutieren wir Bandbreite als kognitive, kulturelle und technische Regel, als eine Regel, die Informationsübertragung pro Zeiteinheit beschränkt. Wir verstehen Wirtschaft, Kultur und Gesellschaft als regelbasiertes evolvierendes System und geben der Bandbreite als generische Regel eine zentrale Rolle. Dabei untersuchen wir theoretisch die wechselwirkenden Prozesse der Ausbeutung und Ausweitung von Bandbreite in Mensch-Maschine-Komplexen. Des Weiteren verweisen wir auf die historische Dimension der digitalisierten Gesellschaft und diskutieren kulturelle Entwicklungen von evolvierten Prothesen. In diesem Zusammenhang formulieren wir eine Genealogie von Gleichheit und Freiheit im Netz. Abschließend betrachten wir zwei Beispiele von evolvierenden Prothesen: Das „Automated Trading“ und die Thematik des „Freundschaftskapitals bei Facebook“. Es zeigt sich, dass sich in beiden Beispielen, so unterschiedlich ihre Implikationen auf ersten Blick auch sind, systemisches Risiko auf ähnliche Art und Weise akkumuliert. Unser Artikel versucht einerseits wesentliche Aspekte der Ökonomie der Bandbreite aufzuzeigen, andererseits erste interdisziplinäre Denkschemata für ebendiese zu entwickeln.

  13. Cell origins and diagnostic accuracy of interleukin 27 in pleural effusions.

    Directory of Open Access Journals (Sweden)

    Wei-Bing Yang

    Full Text Available The objective of the present study was to investigate the presence of interleukin (IL-27 in pleural effusions and to evaluate the diagnostic significance of pleural IL-27. The concentrations of IL-27 were determined in pleural fluids and sera from 68 patients with tuberculous pleural effusion, 63 malignant pleural effusion, 22 infectious pleural effusion, and 21 transudative pleural effusion. Flow cytometry was used to identify which pleural cell types expressed IL-27. It was found that the concentrations of pleural IL-27 in tuberculous group were significantly higher than those in malignant, infectious, and transudative groups, respectively. Pleural CD4(+ T cells, CD8(+ T cells, NK cells, NKT cells, B cells, monocytes, macrophages, and mesothelial cells might be the cell sources for IL-27. IL-27 levels could be used for diagnostic purpose for tuberculous pleural effusion, with the cut off value of 1,007 ng/L, IL-27 had a sensitivity of 92.7% and specificity of 99.1% for differential diagnosing tuberculous pleural effusion from non-tuberculous pleural effusions. Therefore, compared to non-tuberculous pleural effusions, IL-27 appeared to be increased in tuberculous pleural effusion. IL-27 in pleural fluid is a sensitive and specific biomarker for the differential diagnosing tuberculous pleural effusion from pleural effusions with the other causes.

  14. CD1A, D and E gene polymorphisms in a North African population from Morocco.

    Science.gov (United States)

    Aureli, Anna; Oumhani, Khadija; Del Beato, Tiziana; El Aouad, Rajae; Piancatelli, Daniela

    2016-07-01

    CD1 molecules are specialized in capturing and presenting lipids and glycolipids to distinct subsets of T and NKT cells. Glycolipid presentation could play a significant role in the immune response against microbial infections. There are five closely linked CD1 genes in humans, named CD1A, B, C, D, and E, which all show a limited polymorphism. In this study, exon 2 polymorphisms of CD1A, CD1D and CD1E were investigated and allele, genotype and haplotype frequencies of these loci were reported in a Moroccan population. A comparison with allele, genotype and haplotype frequencies observed in other geographic areas was also performed. Results confirmed the presence of ethnic differences in CD1 polymorphism, mainly in CD1D (in this population two additional CD1D variant alleles, CD1D(∗)03 and CD1D(∗)04, were described) and E genes. These data could be useful to evaluate a possible pathogenetic role of CD1 in diseases. Increasing the knowledge in this field may offer possibilities for the development of new immunotherapeutic approaches. PMID:27156638

  15. Status and Progress of a Fault Current Limiting Hts Cable to BE Installed in the con EDISON Grid

    Science.gov (United States)

    Maguire, J.; Folts, D.; Yuan, J.; Henderson, N.; Lindsay, D.; Knoll, D.; Rey, C.; Duckworth, R.; Gouge, M.; Wolff, Z.; Kurtz, S.

    2010-04-01

    In the last decade, significant advances in the performance of second generation (2G) high temperature superconducting wire have made it suitable for commercially viable applications such as electric power cables and fault current limiters. Currently, the U.S. Department of Homeland Security is co-funding the design, development and demonstration of an inherently fault current limiting HTS cable under the Hydra project with American Superconductor and Consolidated Edison. The cable will be approximately 300 m long and is being designed to carry 96 MVA at a distribution level voltage of 13.8 kV. The underground cable will be installed and energized in New York City. The project is led by American Superconductor teamed with Con Edison, Ultera (Southwire and nkt cables joint venture), and Air Liquide. This paper describes the general goals, design criteria, status and progress of the project. Fault current limiting has already been demonstrated in 3 m prototype cables, and test results on a 25 m three-phase cable will be presented. An overview of the concept of a fault current limiting cable and the system advantages of this unique type of cable will be described.

  16. Merozoite surface protein-1 of Plasmodium yoelii fused via an oligosaccharide moiety of cholera toxin B subunit glycoprotein expressed in yeast induced protective immunity against lethal malaria infection in mice.

    Science.gov (United States)

    Miyata, Takeshi; Harakuni, Tetsuya; Taira, Toki; Matsuzaki, Goro; Arakawa, Takeshi

    2012-01-20

    Methylotrophic yeast (Pichia pastoris) secreted cholera toxin B subunit (CTB) predominantly as a biologically active pentamer (PpCTB) with identical ganglioside binding affinity profiles to that of choleragenoid. Unlike choleragenoid, however, the PpCTB did not induce a footpad edema response in mice. Of the two potential glycosylation sites (NIT(4-6) and NKT(90-92)) for this protein, a N-linked oligosaccharide was identified at Asn4. The oligosaccharide, presumed to extend from the lateral circumference of the CTB pentamer ring structure, was exploited as a site-specific anchoring scaffold for the C-terminal 19-kDa merozoite surface protein-1 (MSP1-19) of the rodent malaria parasite, Plasmodium yoelii. Conjugation of MSP1-19 to PpCTB via its oligosaccharide moiety induced higher protective efficacy against lethal parasite infection than conjugation directly to the PpCTB protein body in both intranasal and subcutaneous immunization regimes. Such increased protection was potentially due to the higher antigen loading capacity of CTB achieved when the antigen was linked to the extended branches of the oligosaccharide. This might have allowed the antigen to reside in more spacious molecular environment with less steric hindrance between the constituent molecules of the fusion complex. PMID:22119928

  17. Mere kvalificeret studievalg – mindre frafald?

    DEFF Research Database (Denmark)

    Heilesen, Simon

    2015-01-01

    Artiklen redegør for to forsøg med at anvende MOOC-formatet (Massive Open Online Course) i en dansk, regional sammenhæng. Forsøgene er tænkt som et bud på en mulig vej til at nedbringe studiefrafald gennem bedre information på ungdomsuddannelserne om, hvad et universitetsstudium indebærer. De...... to MOOC-produkter bidrager såvel som supplement til studievalgsvejledningen, som læringsobjekt og som et middel til at markedsføre videregående uddannelser. De to produkter henvender sig endvidere til ansatte i regionens virksomheder og organisationer med formidling af viden og et tilbud om aktivt og...... dialogisk at sætte sig ind i et genstandsfelt. Udviklingen af konceptet rammesættes indledningsvis af en skitsering af studievalgsproblematikken, af MOOC som fænomen, samt af en oversigt over tilsvarende anvendelser af MOOC-formatet. Herefter præsenteres de to uddannelsesdesigns samt brugernes afprøvning og...

  18. The Anti-tumor Immunity of Dendritic Cells Modified by IFN γ Gene on Mice Bearing Ascite Hepatoma Cell H22

    Institute of Scientific and Technical Information of China (English)

    Zi-You CUI; Hong-Yan YANG; You-Tian HUANG; Zhi-min ZHENG; Ming-Yao ZHAO; Zi-Ming DONG

    2005-01-01

    @@ 1 Introduction Dendritc cell (DC)-based cancer vaccines have shown to been effective both in clinical trials and in animal tumor models. Some clinical trials have been on the phase Ⅲ , but some problems are challenging now. The functions of DC from patient with malignant tumor were depressed by tumor-secreting cytokines such as IL-10. it is critical to find out some methods to improve DC differentiation maturation for priming naive T cells and initiating the specific anti-tumor immunity effectively. IFNγ is a pluripotent cytokine that can exert more the expressions of different molecules in various cells. Now, some data have shown that DCs can produce IFNγ and IFNγ can promote the maturation of DCs, which plays very important roles in promoting protective immune response as the same as IFNγ produced in NK and NKT cells. In our research,we transfected IFNγ gene into DCs in order to investigate the effect of IFNγ on DCs and monitor the anti-tumor response of the tumor bearing mice after vaccination by IFNγ-modified DCs.

  19. Die frontotemporale Lobärdegeneration: Ein Syndrom mit variabler klinischer Manifestation

    Directory of Open Access Journals (Sweden)

    Jesse S

    2012-01-01

    Full Text Available Die frontotemporalen Lobärdegenerationen (FTD als dritthäufigste degenerative Demenzform nach der Alzheimer-Demenz und der Lewy-Body-Demenz lassen sich anhand ihres klinischen Profils in 3 Varianten einteilen: (1 Die frontale Verlaufsform (bvFTD mit im Vordergrund stehender Änderung der Persönlichkeit und des Sozialverhaltens, (2 die semantische Demenz (SD mit vornehmlich bitemporaler kortikaler Atrophie und korrespondierend defizitärem Wissen über Wortbedeutungen, allgemeines Faktenwissen sowie einer visuell-gnostischen Störung und (3 die progressive nicht-flüssige Aphasie (PNFA mit einer meist nicht-flüssigen Aphasie und frontal-operkulär betonter zerebraler Atrophie. Die genannten klinischen Symptomatiken der FTD lassen sich mit den üblichen neuropsychologischen Testverfahren zur Erfassung demenzieller Syndrome anfangs nur sehr schwer diagnostizieren, sodass hier quantifizierbare Verhaltens- und Sprachtests eine bessere Diagnosestellung erlauben. Therapeutisch steht die Psychoedukation Angehöriger sowie in die Pflege involvierter Personen im Vordergrund, eine medikamentöse Therapie beschränkt sich auf symptomatische Maßnahmen.

  20. Common variable immunodeficiency diagnosed during the treatment of bronchial asthma: Unusual cause of wheezing

    Directory of Open Access Journals (Sweden)

    Tomohiro Akaba

    2015-01-01

    Full Text Available Common variable immunodeficiency (CVID is the most frequent primary immunodeficiency in adults and children. We herein report a case of CVID, who was misdiagnosed with asthma due to wheezing episodes and relatively late onset. A 51-year-old woman had suffered from recurrent upper and lower airway infection for recent 2 years. She repeated wheezing attacks and was treated as asthma exacerbation triggered by infection. She was referred to our hospital for investigation and treatment. Lung function tests showed no reversibility of FEV1 by β-adrenergic agonist, but the increase of V50/V25. Chest CT showed slight to moderate bronchial wall thickening and bronchiectasis. After that, she suffered from pneumonia with wheezing attacks twice a month, and immunodeficiency was strongly suspected. Her blood tests showed marked decreases of all classes of immunoglobulin and nearly lack of memory B cells, NKT cells and plasmacytoid dendritic cells. She was diagnosed with CVID, and was treated with replacement of gammaglobulin. Thereafter, her wheezing episodes with infection were remarkably improved. Because the delay of diagnosis with CVID likely causes poor mortality and morbidity, a possibility of CVID should be considered in patients with frequent asthma-like symptoms due to recurrent airway infection.

  1. Political Journalism under Pressure - Between Autonomy and Dependence

    Directory of Open Access Journals (Sweden)

    Günther Pallaver

    2010-06-01

    Full Text Available Dieser Beitrag befasst sich mit der zunehmenden Tendenz politischer Eliten, auf die journalistische Berichterstattung und den politischen Journalismus Einfluss zu nehmen. Dabei wird gezeigt, inwieweit dadurch Handlungsspielräume im politischen Journalismus eingeschränkt werden. Untersucht werden insgesamt vier Länder, nämlich die USA, die Bundesrepublik Deutschland, Österreich und Italien. Beim diesem Vergleich stellt sich die Frage nach der Bedeutung struktureller Unterschiede angesichts der verschiedenen politischen Systeme in den untersuchten Ländern (z. B. präsidentielles vs. parlamentarische Systeme, parteien- vs. medienzentrierte Systeme. Abschließend geht es um Überlegungen zu unterschiedlichen privatrechtlich organisierten oder dualen Mediensystemen im Zusammenhang strategischer Einflussnahmen und Abwehrmaßnahmen. In this paper the proposition to be tested is whether the political elites’ attempt to exert influence on day-to-day news coverage and thus on political journalism is increasing and whether as a result political journalism’s autonomous leeway is continually diminishing. The countries examined are the United States, Germany, Austria and Italy. In this context the question whether there are structural differences due to the diverse political systems of the countries under consideration (presidential vs. parliamentary systems; systems centred more on parties vs. systems centred more on the media will also be investigated. Last but not least, the role of different media systems will be considered, too (media under private law, dual systems including the Italian version.

  2. Knowledge and Accountability in Aristotle - Wissen und Zurechenbarkeit bei Aristoteles

    Directory of Open Access Journals (Sweden)

    Martin F. Meyer

    2010-07-01

    Full Text Available This contribution is intended to show that Aristotle was the first European philosopher to provide a systematic analysis of the so-called accountability problem. In the third book of his Nicomachean Ethics, he lays particular stress on the central role of knowledge: deficiencies in the knowledge of the perpetrator mean that we do not hold him responsible for his actions, or only to a limited extent; he is thus either not at all, or only to a certain degree, accountable for his acts.Der Beitrag soll zeigen, daß Aristoteles als erster europäischer Denker eine systematische Analyse der sog. Zurechnungsproblematik vorgelegt hat. Im 3. Buch seiner Nikomachischen Ethik hebt er dabei v. a. auf die zentrale Rolle des Wissens ab: Wissensmängel auf Seiten des Täters führen dazu, daß wir ihn nicht oder nur eingeschränkt für seine Handlungen verantwortlich machen; ihm also seine Taten entweder gar nicht oder nur begrenzt zurechnen.

  3. Th17/IL-17A might play a protective role in chronic lymphocytic leukemia immunity.

    Directory of Open Access Journals (Sweden)

    Iwona Hus

    Full Text Available Th17 cells, a recently discovered subset of T helper cells that secrete IL-17A, can affect the inflammation process autoimmune and cancer diseases development. The purpose of this study was to evaluate the role of Th17 cells and IL17A in biology of CLL. The study group included 294 untreated CLL patients in different clinical stages. Here, we show that higher Th17 and IL-17A values were associated with less advanced clinical stage of CLL. Th17 cells' percentages in PB were lower in patients who died due to CLL during follow-up due to CLL (as compared to surviving patients and in patients responding to first-line therapy with fludarabine-based regimens (as compared to non-responders. IL-17A inversely correlated with the time from CLL diagnosis to the start of therapy and was lower in patients who required treatment during follow-up. Th-17 and IL-17A values were lower in patients with adverse prognostic factors (17p and 11q deletion, CD38 and ZAP-70 expression. CLL patients with detectable IL-17A mRNA in T cells were in Rai Stage 0 and negative for both ZAP-70 and CD38 expression. Th17 percentages positively correlated with iNKT and adversely with Treg cells. The results of this study suggest that Th17 may play a beneficial role in CLL immunity.

  4. Ludology as Game Research in Language Pedagogy Studies. Ludologie als Spielforschung – angewandt in der Fremdsprachendidaktik

    Directory of Open Access Journals (Sweden)

    Augustyn Surdyk

    2008-01-01

    Full Text Available Das Ziel des Artikels ist die Präsentation der grundlegenden Voraussetzungen der Ludologie, die sich mit der Erforschung von Spielen und ihrer Anwendung im Fremdsprachenunterricht und in der angewandten Linguistik beschäftigt.Diese Wissenschaftsdisziplin wird in Polen durch die landesweit erste ludologische Gesellschaft vertreten und gefördert („Polnische Gesellschaft zur Spielforschung“. Das Ziel der Gesellschaft ist es, Wissen über Spiele, sowohl in theoretischer als auch in praktischer Form zu entwickeln und zu vermitteln. Die Gesellschaft vereinigt Wissenschaftler und Studierende zahlreicher Universitäten, die verschiedene Disziplinen vertreten (Sprachwissenschaftler, Literaturwissenschaftler, Kultur­wissenschaftler, Soziologen, Psychologen, Philosophen, Historiker, Ökonomisten, Informatiker und Vertreter anderer exakter wie auch humanistischer Disziplinen sowie Spieler und Schöpfer der Spiele, welche sich mit Spielthemen in einem weiten Sinn beschäftigen, mit besonderer Berück­sichtigung der role-playing games und der Computerspiele. Doch im Gegensatz zur Digital Games Research Association beschränkt sich das Objekt der wissenschaftlichen Interessen der Mitglieder der Polnischen Gesellschaft zur Spielforschung nicht ausschließlich auf die Computerspiele.Der Artikel präsentiert ein ausgezeichnetes Beispiel narrativer role-playing games als einen Typ von Spielen, die den Gegenstand interdisziplinärer Forschungen im Rahmen der Ludologie bilden könnten. Die Darstellung bietet gleichzeitig ein Beispiel der vom Autor im Fremdsprachenunterricht als innovativ angewandten Technik der „Role-Playing Games“ (RPG.

  5. Kleinwuchs – Differenzialdiagnose und therapeutische Optionen

    Directory of Open Access Journals (Sweden)

    Kapelari K

    2015-01-01

    Full Text Available Auffälligkeiten des Wachstums eines Kindes gehören zu den häufigsten Fragestellungen in der Pädiatrie. Die fachlich korrekte Beurteilung im individuellen Fall setzt eine gewissenhafte Erfassung der auxologischen Verlaufsparameter, die profunde Kenntnis des physiologischen Wachstumsverlaufes von Kindern und das Wissen über die Vielzahl von möglichen Wachstumsstörungen voraus. Das Wachstum von Kindern unterliegt einer großen natürlichen Variationsbreite – ein Umstand, der die Abgrenzung von sog. Normvarianten des Wachstums von nach heutigem Wissensstand behandelbaren und nichtbehandelbaren Wachstumsstörungen erschwert. Wichtige Voraussetzung für eine Diagnose stellen die Erfassung der Parameter bei Geburt zur Erkennung einer SGA-Konstellation, das Wissen über die Körpergröße der biologischen Eltern, die Dokumentation des Wachstumsverlaufes eines Kindes durch Führen einer geschlechts- und bevölkerungsspezifischen Perzentilenkurve und das Erkennen einer Disproportion, ebenfalls bestätigt durch Eintragung der Sitzhöhen/Beinlängen-Ratio in eine Perzentilenkurve, dar. Für einige definierte Wachstumsstörungen stehen Therapien zur Verfügung. Über 40 Jahre lang stand zur Behandlung lediglich Wachstumshormon zur Verfügung, seit 1985 in rekombinanter Form und somit praktisch unbeschränkt verfügbar. Seit der Markteinführung von rekombinantem IGF-1 ergeben sich neue therapeutische Optionen.

  6. Expression of CD11c Is Associated with Unconventional Activated T Cell Subsets with High Migratory Potential

    Science.gov (United States)

    Cantero, Jon; Tarrats, Antoni; Fernández, Marco Antonio; Sumoy, Lauro; Rodolosse, Annie; McSorley, Stephen J.

    2016-01-01

    CD11c is an α integrin classically employed to define myeloid dendritic cells. Although there is little information about CD11c expression on human T cells, mouse models have shown an association of CD11c expression with functionally relevant T cell subsets. In the context of genital tract infection, we have previously observed increased expression of CD11c in circulating T cells from mice and women. Microarray analyses of activated effector T cells expressing CD11c derived from naïve mice demonstrated enrichment for natural killer (NK) associated genes. Here we find that murine CD11c+ T cells analyzed by flow cytometry display markers associated with non-conventional T cell subsets, including γδ T cells and invariant natural killer T (iNKT) cells. However, in women, only γδ T cells and CD8+ T cells were enriched within the CD11c fraction of blood and cervical tissue. These CD11c+ cells were highly activated and had greater interferon (IFN)-γ secretory capacity than CD11c- T cells. Furthermore, circulating CD11c+ T cells were associated with the expression of multiple adhesion molecules in women, suggesting that these cells have high tissue homing potential. These data suggest that CD11c expression distinguishes a population of circulating T cells during bacterial infection with innate capacity and mucosal homing potential. PMID:27119555

  7. Common variable immunodeficiency diagnosed during the treatment of bronchial asthma: Unusual cause of wheezing.

    Science.gov (United States)

    Akaba, Tomohiro; Kondo, Mitsuko; Toriyama, Midori; Kubo, Ayako; Hara, Kaori; Yamada, Takeshi; Yoshinaga, Kentaro; Tamaoki, Jun

    2015-01-01

    Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency in adults and children. We herein report a case of CVID, who was misdiagnosed with asthma due to wheezing episodes and relatively late onset. A 51-year-old woman had suffered from recurrent upper and lower airway infection for recent 2 years. She repeated wheezing attacks and was treated as asthma exacerbation triggered by infection. She was referred to our hospital for investigation and treatment. Lung function tests showed no reversibility of FEV1 by β-adrenergic agonist, but the increase of V50/V25. Chest CT showed slight to moderate bronchial wall thickening and bronchiectasis. After that, she suffered from pneumonia with wheezing attacks twice a month, and immunodeficiency was strongly suspected. Her blood tests showed marked decreases of all classes of immunoglobulin and nearly lack of memory B cells, NKT cells and plasmacytoid dendritic cells. She was diagnosed with CVID, and was treated with replacement of gammaglobulin. Thereafter, her wheezing episodes with infection were remarkably improved. Because the delay of diagnosis with CVID likely causes poor mortality and morbidity, a possibility of CVID should be considered in patients with frequent asthma-like symptoms due to recurrent airway infection. PMID:26744651

  8. in Human Liver Diseases

    Directory of Open Access Journals (Sweden)

    Minoru Fujimoto

    2010-01-01

    Full Text Available Toll-like receptor (TLR signaling pathways are strictly coordinated by several mechanisms to regulate adequate innate immune responses. Recent lines of evidence indicate that the suppressor of cytokine signaling (SOCS family proteins, originally identified as negative-feedback regulators in cytokine signaling, are involved in the regulation of TLR-mediated immune responses. SOCS1, a member of SOCS family, is strongly induced upon TLR stimulation. Cells lacking SOCS1 are hyperresponsive to TLR stimulation. Thus, SOCS1 is an important regulator for both cytokine and TLR-induced responses. As an immune organ, the liver contains various types of immune cells such as T cells, NK cells, NKT cells, and Kupffer cells and is continuously challenged with gut-derived bacterial and dietary antigens. SOCS1 may be implicated in pathophysiology of the liver. The studies using SOCS1-deficient mice revealed that endogenous SOCS1 is critical for the prevention of liver diseases such as hepatitis, cirrhosis, and cancers. Recent studies on humans suggest that SOCS1 is involved in the development of various liver disorders in humans. Thus, SOCS1 and other SOCS proteins are potential targets for the therapy of human liver diseases.

  9. „Kinder kriegen die Leute immer…“ “People will always have children…”

    Directory of Open Access Journals (Sweden)

    Susanne Benöhr-Laqueur

    2007-07-01

    Full Text Available Das Buch basiert auf Beiträgen zur internationalen Tagung „The Gender of Politics: The Example of Reproduction Policies in Austria, Finland, Portugal, Romania, Russia and the US“, die vom 13. März bis 15. März 2003 in Wien stattgefunden hat. Der Sammelband enthält vierzehn Aufsätze von Wissenschaftlerinnen aus sechs Ländern zu den Themen „Abtreibung“, „Reproduktionsmedizin“ und „Kinderbetreuung”. Vor dem Hintergrund der aktuellen bundesdeutschen Debatte um die „Kinderkrippen“ und das „Elterngeld“ ist das Werk uneingeschränkt zu empfehlen.The book is based on the international conference, “The Gender of Politics: The Example of Reproduction Policies in Austria, Finland, Portugal, Romania, Russia and the US,” which took place in Vienna on March 13-15, 2003. The collected volume contains fourteen essays by scholars from six countries and cover themes such as “abortion,” “reproductive medicine,” and “childcare.” This book is highly recommended, particularly in the context of the current debates in the Federal Republic on “daycares” and “parental benefits.”

  10. Cancer Immunosurveillance by Tissue-Resident Innate Lymphoid Cells and Innate-like T Cells.

    Science.gov (United States)

    Dadi, Saïda; Chhangawala, Sagar; Whitlock, Benjamin M; Franklin, Ruth A; Luo, Chong T; Oh, Soyoung A; Toure, Ahmed; Pritykin, Yuri; Huse, Morgan; Leslie, Christina S; Li, Ming O

    2016-01-28

    Malignancy can be suppressed by the immune system in a process termed immunosurveillance. However, to what extent immunosurveillance occurs in spontaneous cancers and the composition of participating cell types remains obscure. Here, we show that cell transformation triggers a tissue-resident lymphocyte response in oncogene-induced murine cancer models. Non-circulating cytotoxic lymphocytes, derived from innate, T cell receptor (TCR)αβ, and TCRγδ lineages, expand in early tumors. Characterized by high expression of NK1.1, CD49a, and CD103, these cells share a gene-expression signature distinct from those of conventional NK cells, T cells, and invariant NKT cells. Generation of these lymphocytes is dependent on the cytokine IL-15, but not the transcription factor Nfil3 that is required for the differentiation of tumor-infiltrating NK cells, and IL-15 deficiency, but not Nfil3 deficiency, results in accelerated tumor growth. These findings reveal a tumor-elicited immunosurveillance mechanism that engages unconventional type-1-like innate lymphoid cells and type 1 innate-like T cells.

  11. A radio-resistant perforin-expressing lymphoid population controls allogeneic T cell engraftment, activation, and onset of graft-versus-host disease in mice.

    Science.gov (United States)

    Davis, Joanne E; Harvey, Michael; Gherardin, Nicholas A; Koldej, Rachel; Huntington, Nicholas; Neeson, Paul; Trapani, Joseph A; Ritchie, David S

    2015-02-01

    Immunosuppressive pretransplantation conditioning is essential for donor cell engraftment in allogeneic bone marrow transplantation (BMT). The role of residual postconditioning recipient immunity in determining engraftment is poorly understood. We examined the role of recipient perforin in the kinetics of donor cell engraftment. MHC-mismatched BMT mouse models demonstrated that both the rate and proportion of donor lymphoid cell engraftment and expansion of effector memory donor T cells in both spleen and BM were significantly increased within 5 to 7 days post-BMT in perforin-deficient (pfn(-/-)) recipients, compared with wild-type. In wild-type recipients, depletion of natural killer (NK) cells before BMT enhanced donor lymphoid cell engraftment to that seen in pfn(-/-) recipients. This demonstrated that a perforin-dependent, NK-mediated, host-versus-graft (HVG) effect limits the rate of donor engraftment and T cell activation. Radiation-resistant natural killer T (NKT) cells survived in the BM of lethally irradiated mice and may drive NK cell activation, resulting in the HVG effect. Furthermore, reduced pretransplant irradiation doses in pfn(-/-) recipients permitted long-term donor lymphoid cell engraftment. These findings suggest that suppression of perforin activity or selective depletion of recipient NK cells before BMT could be used to improve donor stem cell engraftment, in turn allowing for the reduction of pretransplant conditioning.

  12. Der Einfluss von personeller Einkommensverteilung auf die „Great Depression“ und die „Great Recession“

    Directory of Open Access Journals (Sweden)

    Stefan Trappl

    2015-12-01

    Full Text Available Der Einfluss gestiegener Einkommensungleichheit auf die „Great Depression“ und die „Great Recession“ wurde mehrfach postuliert (Galbraith 1954/2009; Eccles 1951; Rajan 2010; Stiglitz 2012; Piketty 2014. Konkrete empirische Arbeiten zum Zusammenhang zwischen Einkommensverteilung und dem Entstehen von Wirtschaftskrisen gibt es aber bislang wenige. Kumhof/Ranciere (2010 überprüften die von Rajan (2010 aufgestellte Hypothese, die einen entsprechenden Zusammenhang postuliert, mittels Modellrechnung. Bordo/Meissner (2012 und darauf aufbauend Gu/Huang (2014 verwendeten unterschiedliche Regressionsmodelle in Bezug auf einen entsprechenden Zusammenhang, ohne jedoch eindeutige Ergebnisse zu liefern. Die vorliegende Arbeit schließt an diese Arbeiten an, beschränkt die Untersuchung allerdings auf Staaten, für die Daten für die letzten hundert Jahre verfügbar sind, und untersucht zudem explizit die Zeiträume um die beiden größten Krisen der letzten hundert Jahre, die „Great Depression“ und die „Great Recession“. Die Auswertungen zeigen, dass die personelle Einkommensverteilung ein guter Prädiktor für die Kriseneintrittswahrscheinlichkeit ist.

  13. Permanente sakrale Neuromodulation mittels InterStim®: Ergebnisse einer Anwendungsbefragung zu aktuellen technischen Entwicklungen

    Directory of Open Access Journals (Sweden)

    Sievert KD

    2007-01-01

    Full Text Available In den vergangenen über 20 Jahren wurde die sakrale Neuromodulation als klinische Therapie etabliert. Die anfängliche Indikation wurde ständig erweitert und umfaßt heute verschiedene Formen der Blasen- und Stuhlentleerungsstörung sowie eingeschränkt die Schmerztherapie im kleinen Becken. Fortwährend wurde die Technik der Implantation verbessert und die zur Verfügung stehende Hardware verkleinert. Als Resultat der konsequenten Weiterentwicklung wurde im letzten Jahr der miniaturisierte InterStim® II vorgestellt und dessen klinischer Einsatz durch versierte Operateure der unterschiedlichsten Disziplinen mittels einer internetbasierten Befragung beurteilt. Durch die Verwendung des InterStim® II werden im Vergleich zum InterStim® die operative Invasivität mit der Operationszeit und daraus resultierend der postoperative Schmerz gesenkt. Die neue Fernbedienung läßt einen weiteren Anstieg der Akzeptanz erwarten, da durch das Display der Fernbedienung der Patient die Einstellungen kontrollieren kann. Die weitere Miniaturisierung mit gleichzeitig erweiterter Programmierbarkeit des Implantates, der direkten Verbindung von Elektrode und Impulsgeber mit einer einzelnen Schraube verbessert die Option der Neuromodulation weiter. Die Entwicklungen unterstützen den minimal-invasiven Aspekt der InterStim®-Therapie, wodurch die Möglichkeit der ambulanten Therapieoption gegeben sein könnte. Es bleibt abzuwarten, ob die Therapie der Neuromodulation durch die erweiterten Programmiermöglichkeiten für den einzelnen Patienten in Zukunft noch individueller im chronischen Einsatz optimiert werden kann.

  14. Evaluating cryostat performance for naval applications

    Science.gov (United States)

    Knoll, David; Willen, Dag; Fesmire, James; Johnson, Wesley; Smith, Jonathan; Meneghelli, Barry; Demko, Jonathan; George, Daniel; Fowler, Brian; Huber, Patti

    2012-06-01

    The Navy intends to use High Temperature Superconducting Degaussing (HTSDG) coil systems on future Navy platforms. The Navy Metalworking Center (NMC) is leading a team that is addressing cryostat configuration and manufacturing issues associated with fabricating long lengths of flexible, vacuum-jacketed cryostats that meet Navy shipboard performance requirements. The project includes provisions to evaluate the reliability performance, as well as proofing of fabrication techniques. Navy cryostat performance specifications include less than 1 Wm-1 heat loss, 2 MPa working pressure, and a 25-year vacuum life. Cryostat multilayer insulation (MLI) systems developed on the project have been validated using a standardized cryogenic test facility and implemented on 5-meterlong test samples. Performance data from these test samples, which were characterized using both LN2 boiloff and flow-through measurement techniques, will be presented. NMC is working with an Integrated Project Team consisting of Naval Sea Systems Command, Naval Surface Warfare Center-Carderock Division, Southwire Company, nkt cables, Oak Ridge National Laboratory (ORNL), ASRC Aerospace, and NASA Kennedy Space Center (NASA-KSC) to complete these efforts. Approved for public release; distribution is unlimited. This material is submitted with the understanding that right of reproduction for governmental purposes is reserved for the Office of Naval Research, Arlington, Virginia 22203-1995.

  15. Wie wissenschaftlich ist der Evolutionsgedanke?

    Science.gov (United States)

    Vollmer, Gerhard

    Darwin war ein besonnener Mann; alles Aufsehen war ihm zuwider. Trotzdem hat er eine Revolution ausgelöst, deren Wirkung nicht auf die Biologie beschränkt blieb. Seine Theorie lässt sich in fünf Teiltheorien zerlegen, die sich durch die Begriffe Artenwandel, Verwandtschaft alles Lebendigen und gemeinsamer Ursprung, Artenaufspaltung und Artenvielfalt, Gradualismus, natürliche Auslese charakterisieren lassen. Dadurch wurden mehrere religiöse und weitere weltanschauliche Überzeugungen in Frage gestellt. Deshalb wird die Evolutionstheorie auch heute noch vielfach kritisiert, ja bekämpft. Die Vorwürfe lassen sich ordnen nach den Kriterien, mit denen wir erfahrungswissenschaftliche Theorien beurteilen. Haltbar ist daran nur, dass es für die Evolutionstheorie zwar beliebig viele Bestätigungen gibt, aber nur wenige Widerlegungsmöglichkeiten. Durch die neuerdings entwickelten und durchgeführten Evolutionsexperimente ist die empirische Situation allerdings deutlich besser geworden. Am (erfahrungs)wissenschaftlichen Charakter der Evolutionstheorie besteht deshalb kein Zweifel.

  16. 400 MW grid connection to the Anholt offshore wind farm in a single 220 kV cable system

    Energy Technology Data Exchange (ETDEWEB)

    Kvarts, Thomas [Energinet.dk (Denmark); Bailleul, March; Douima, Youssef; Petitot, Francois [General Cable Group, Silec, Cachan (France); Domingo, Jose M. [General Cable Group (Spain); Jensen, Anders; Salwin, Sven T. [nkt cables (Denmark)

    2011-07-01

    In 2012, the so far largest wind farm in Denmark, Anholt offshore wind farm, will bring 400 MW more electrical power to Denmark. To that effect, Energinet.dk, Denmark's transmission system operator, will install and operate an 85-km-long grid connection from the Anholt platform to the Danish electricity transmission grid. This connection is composed of: (1) a single 24 km 245 kV submarine, 3 core cable, delivered and installed by nkt cables, and (2) a 60 km 245 kV underground cable system, delivered by the General Cable group. (3) an offshore transformer platform. (4) reactive compensation and transformation onshore. This aim of this paper is to present the characteristics of this project, the first at 245 kV in Denmark, and one of the first 245 kV 3 core submarine cables worldwide. We will first discuss the reasons that prevailed in defining the link's design: routes, voltage, cables dimensioning, impact of capitalized losses etc. Then, the submarine and underground cable systems' characteristics and necessary type test are presented. Finally, we present an overview of the actual implementation of each solution. (orig.)

  17. Crystal structure of extracellular domain of human lectin-like transcript 1 (LLT1), the ligand for natural killer receptor-P1A.

    Science.gov (United States)

    Kita, Shunsuke; Matsubara, Haruki; Kasai, Yoshiyuki; Tamaoki, Takaharu; Okabe, Yuki; Fukuhara, Hideo; Kamishikiryo, Jun; Krayukhina, Elena; Uchiyama, Susumu; Ose, Toyoyuki; Kuroki, Kimiko; Maenaka, Katsumi

    2015-06-01

    Emerging evidence has revealed the pivotal roles of C-type lectin-like receptors (CTLRs) in the regulation of a wide range of immune responses. Human natural killer cell receptor-P1A (NKRP1A) is one of the CTLRs and recognizes another CTLR, lectin-like transcript 1 (LLT1) on target cells to control NK, NKT and Th17 cells. The structural basis for the NKRP1A-LLT1 interaction was limitedly understood. Here, we report the crystal structure of the ectodomain of LLT1. The plausible receptor-binding face of the C-type lectin-like domain is flat, and forms an extended β-sheet. The residues of this face are relatively conserved with another CTLR, keratinocyte-associated C-type lectin, which binds to the CTLR member, NKp65. A LLT1-NKRP1A complex model, prepared using the crystal structures of LLT1 and the keratinocyte-associated C-type lectin-NKp65 complex, reasonably satisfies the charge consistency and the conformational complementarity to explain a previous mutagenesis study. Furthermore, crystal packing and analytical ultracentrifugation revealed dimer formation, which supports a complex model. Our results provide structural insights for understanding the binding modes and signal transduction mechanisms, which are likely to be conserved in the CTLR family, and for further rational drug design towards regulating the LLT1 function. PMID:25826155

  18. Primary extranodal natural killer/T-cell lymphoma of bronchus and lung: A case report and review of literature.

    Science.gov (United States)

    Chien, Chu-Chun; Lee, Herng-Sheng; Lin, Min-Hsi; Hsieh, Pin-Pen

    2016-01-01

    Primary pulmonary non-Hodgkin's lymphoma (NHL) is very rare. It represents less than 1% of all NHL, and 0.5-1% of all primary pulmonary malignancies. Almost all cases of primary pulmonary NHL originate from B-cell lineage. We present a case of a 53-year-old man with primary extranodal NK/T-cell lymphoma of the bronchus and lung, presented progressive dyspnea caused by right lower lung consolidation, and pleural effusion. Initial chest computed tomography suggested advanced lung cancer. Bronchofiberscopy showed a polypoid tumor on which a biopsy was performed. Histologically, the diffusely infiltrative atypical cells were positive for cytoplasmic CD3, CD56, granzyme B, and negative for cytokeratin, CD20 immunostains, suggesting NK/T cell lineages. In situ hybridization for Epstein-Barr virus encoded ribonucleic acid (EBER) was positive. Herein, we discuss the clinicopathological features of this case and review the literature on primary extranodal NK/T-cell lymphoma of the lung. Compared with other patients, who died after the first cycle of chemotherapy and/or within three months, our patient had longer survival under aggressive chemotherapy and auto-peripheral blood stem cell transplantation. PMID:26816549

  19. Die andere Geschichte. Quellen zur Geschlechtergeschichte aus drei Jahrtausenden The other history. Sources of gender history from the millenia

    Directory of Open Access Journals (Sweden)

    Arne Duncker

    2005-11-01

    Full Text Available Das im Schroedel-Verlag erschienene sehr informative Quellen- und Arbeitsbuch zur „Geschlechtergeschichte“ ist als Lehrbuch für die Sekundarstufe II konzipiert und darüber hinaus sicherlich in vielen Fällen auch als Einführungslektüre für Studienanfänger/-innen und sonstige Einsteiger in das Forschungsgebiet Geschlechtergeschichte uneingeschränkt empfehlenswert. Das Werk behandelt in insgesamt acht Kapiteln Schwerpunktthemen der Frauen- und Geschlechtergeschichte, von der griechischen Antike über Mittelalter und Aufklärung bis zur Gegenwart. Neben „klassischen“ Fragestellungen der Frauenforschung – wie Matriarchat, Frauenklöster, Hexenverfolgung, Ehepflichten, philosophische Diskurse des 18. Jahrhunderts – sind dabei insbesondere auch die neueren und neuesten Ansätze der Geschlechterforschung einbezogen, Themen wie Duellforschung, wie Körper- und Kleidungsvorstellungen, auch Definitionsversuche des Geschlechts als „soziokulturelles Daseinskonstrukt“ sowie Fragen der Intersexualität und Transidentität. Eine besondere Stärke in der Aufbereitung des Stoffes – gerade auch im Vergleich mit ähnlicher Einführungslektüre – liegt in dem ausgesprochen quellenzentrierten Vorgehen. Oft lässt das vorliegende Sammelwerk die zeitgenössischen Quellen selber zu Wort kommen und beschränkt dabei die Kommentierungen dieser Quellen auf das unerlässlich Notwendige. Dies trägt zu einer vorzüglichen, didaktisch gut aufbereiteten und sehr lebendigen Darstellungsweise bei.This very informative book has been published by Schroedel-Verlag and offers both source material and working-tasks on “gender history”. It is teaching material for advanced classes in secondary schools and will without doubt be useful as introductory reading for students and other people interested in the field of gender history. The book consists of eight chapters that deal with main topics in women’s and gender history, ranging from Greek antiquity

  20. Immune mechanisms in acetaminophen-induced acute liver failure.

    Science.gov (United States)

    Krenkel, Oliver; Mossanen, Jana C; Tacke, Frank

    2014-12-01

    An overdose of acetaminophen (N-acetyl-p-aminophenol, APAP), also termed paracetamol, can cause severe liver damage, ultimately leading to acute liver failure (ALF) with the need of liver transplantation. APAP is rapidly taken up from the intestine and metabolized in hepatocytes. A small fraction of the metabolized APAP forms cytotoxic mitochondrial protein adducts, leading to hepatocyte necrosis. The course of disease is not only critically influenced by dose of APAP and the initial hepatocyte damage, but also by the inflammatory response following acetaminophen-induced liver injury (AILI). As revealed by mouse models of AILI and corresponding translational studies in ALF patients, necrotic hepatocytes release danger-associated-molecular patterns (DAMPs), which are recognized by resident hepatic macrophages, Kupffer cell (KC), and neutrophils, leading to the activation of these cells. Activated hepatic macrophages release various proinflammatory cytokines, such as TNF-α or IL-1β, as well as chemokines (e.g., CCL2) thereby further enhancing inflammation and increasing the influx of immune cells, like bone-marrow derived monocytes and neutrophils. Monocytes are mainly recruited via their receptor CCR2 and aggravate inflammation. Infiltrating monocytes, however, can mature into monocyte-derived macrophages (MoMF), which are, in cooperation with neutrophils, also involved in the resolution of inflammation. Besides macrophages and neutrophils, distinct lymphocyte populations, especially γδ T cells, are also linked to the inflammatory response following an APAP overdose. Natural killer (NK), natural killer T (NKT) and T cells possibly further perpetuate inflammation in AILI. Understanding the complex interplay of immune cell subsets in experimental models and defining their functional involvement in disease progression is essential to identify novel therapeutic targets for human disease. PMID:25568858

  1. Selective destruction of mouse islet beta cells by human T lymphocytes in a newly-established humanized type 1 diabetic model

    International Nuclear Information System (INIS)

    Research highlights: → Establish a human immune-mediated type 1 diabetic model in NOD-scid IL2rγnull mice. → Using the irradiated diabetic NOD mouse spleen mononuclear cells as trigger. → The islet β cells were selectively destroyed by infiltrated human T cells. → The model can facilitate translational research to find a cure for type 1 diabetes. -- Abstract: Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that leads to the loss of insulin-producing β cells. The optimal preclinical testing of promising therapies would be aided by a humanized immune-mediated T1D model. We develop this model in NOD-scid IL2rγnull mice. The selective destruction of pancreatic islet β cells was mediated by human T lymphocytes after an initial trigger was supplied by the injection of irradiated spleen mononuclear cells (SMC) from diabetic nonobese diabetic (NOD) mice. This resulted in severe insulitis, a marked loss of total β-cell mass, and other related phenotypes of T1D. The migration of human T cells to pancreatic islets was controlled by the β cell-produced highly conserved chemokine stromal cell-derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor (CXCR) 4, as demonstrated by in vivo blocking experiments using antibody to CXCR4. The specificity of humanized T cell-mediated immune responses against islet β cells was generated by the local inflammatory microenvironment in pancreatic islets including human CD4+ T cell infiltration and clonal expansion, and the mouse islet β-cell-derived CD1d-mediated human iNKT activation. The selective destruction of mouse islet β cells by a human T cell-mediated immune response in this humanized T1D model can mimic those observed in T1D patients. This model can provide a valuable tool for translational research into T1D.

  2. Organic anion and cation SLC22 "drug" transporter (Oat1, Oat3, and Oct1 regulation during development and maturation of the kidney proximal tubule.

    Directory of Open Access Journals (Sweden)

    Thomas F Gallegos

    Full Text Available Proper physiological function in the pre- and post-natal proximal tubule of the kidney depends upon the acquisition of selective permeability, apical-basolateral epithelial polarity and the expression of key transporters, including those involved in metabolite, toxin and drug handling. Particularly important are the SLC22 family of transporters, including the organic anion transporters Oat1 (originally identified as NKT and Oat3 as well as the organic cation transporter Oct1. In ex vivo cultures of metanephric mesenchyme (MM; the embryonic progenitor tissue of the nephron Oat function was evident before completion of nephron segmentation and corresponded with the maturation of tight junctions as measured biochemically by detergent extractability of the tight junction protein, ZO-1. Examination of available time series microarray data sets in the context of development and differentiation of the proximal tubule (derived from both in vivo and in vitro/ex vivo developing nephrons allowed for correlation of gene expression data to biochemically and functionally defined states of development. This bioinformatic analysis yielded a network of genes with connectivity biased toward Hnf4α (but including Hnf1α, hyaluronic acid-CD44, and notch pathways. Intriguingly, the Oat1 and Oat3 genes were found to have strong temporal co-expression with Hnf4α in the cultured MM supporting the notion of some connection between the transporters and this transcription factor. Taken together with the ChIP-qPCR finding that Hnf4α occupies Oat1, Oat3, and Oct1 proximal promoters in the in vivo differentiating rat kidney, the data suggest a network of genes with Hnf4α at its center plays a role in regulating the terminal differentiation and capacity for drug and toxin handling by the nascent proximal tubule of the kidney.

  3. A new basaltic glass microanalytical reference material for multiple techniques

    Science.gov (United States)

    Wilson, Steve; Koenig, Alan; Lowers, Heather

    2012-01-01

    The U.S. Geological Survey (USGS) has been producing reference materials since the 1950s. Over 50 materials have been developed to cover bulk rock, sediment, and soils for the geological community. These materials are used globally in geochemistry, environmental, and analytical laboratories that perform bulk chemistry and/or microanalysis for instrument calibration and quality assurance testing. To answer the growing demand for higher spatial resolution and sensitivity, there is a need to create a new generation of microanalytical reference materials suitable for a variety of techniques, such as scanning electron microscopy/X-ray spectrometry (SEM/EDS), electron probe microanalysis (EPMA), laser ablation inductively coupled mass spectrometry (LA-ICP-MS), and secondary ion mass spectrometry (SIMS). As such, the microanalytical reference material (MRM) needs to be stable under the beam, be homogeneous at scales of better than 10–25 micrometers for the major to ultra-trace element level, and contain all of the analytes (elements or isotopes) of interest. Previous development of basaltic glasses intended for LA-ICP-MS has resulted in a synthetic basaltic matrix series of glasses (USGS GS-series) and a natural basalt series of glasses (BCR-1G, BHVO-2G, and NKT-1G). These materials have been useful for the LA-ICP-MS community but were not originally intended for use by the electron or ion beam community. A material developed from start to finish with intended use in multiple microanalytical instruments would be useful for inter-laboratory and inter-instrument platform comparisons. This article summarizes the experiments undertaken to produce a basalt glass reference material suitable for distribution as a multiple-technique round robin material. The goal of the analytical work presented here is to demonstrate that the elemental homogeneity of the new glass is acceptable for its use as a reference material. Because the round robin exercise is still underway, only

  4. Expression of the SLAM family of receptors adapter EAT-2 as a novel strategy for enhancing beneficial immune responses to vaccine antigens.

    Science.gov (United States)

    Aldhamen, Yasser A; Appledorn, Daniel M; Seregin, Sergey S; Liu, Chyong-jy J; Schuldt, Nathaniel J; Godbehere, Sarah; Amalfitano, Andrea

    2011-01-15

    Recent studies have shown that activation of the signaling lymphocytic activation molecule (SLAM) family of receptors plays an important role in several aspects of immune regulation. However, translation of this knowledge into a useful clinical application has not been undertaken. One important area where SLAM-mediated immune regulation may have keen importance is in the field of vaccinology. Because SLAM signaling plays such a critical role in the innate and adaptive immunity, we endeavored to develop a strategy to improve the efficacy of vaccines by incorporation of proteins known to be important in SLAM-mediated signaling. In this study, we hypothesized that coexpression of the SLAM adapter EWS-FLI1-activated transcript 2 (EAT-2) along with a pathogen-derived Ag would facilitate induction of beneficial innate immune responses, resulting in improved induction of Ag-specific adaptive immune responses. To test this hypothesis, we used rAd5 vector-based vaccines expressing murine EAT-2, or the HIV-1-derived Ag Gag. Compared with appropriate controls, rAd5 vectors expressing EAT-2 facilitated bystander activation of NK, NKT, B, and T cells early after their administration into animals. EAT-2 overexpression also augments the expression of APC (macrophages and dendritic cells) surface markers. Indeed, this multitiered activation of the innate immune system by vaccine-mediated EAT-2 expression enhanced the induction of Ag-specific cellular immune responses. Because both mice and humans express highly conserved EAT-2 adapters, our results suggest that human vaccination strategies that specifically facilitate SLAM signaling may improve vaccine potency when targeting HIV Ags specifically, as well as numerous other vaccine targets in general.

  5. Measurement of Thermal Dependencies of PBG Fiber Properties

    International Nuclear Information System (INIS)

    Photonic crystal fibers (PCFs) represent a class of optical fibers which have a wide spectrum of applications in the telecom and sensing industries. Currently, the Advanced Accelerator Research Department at SLAC is developing photonic bandgap particle accelerators, which are photonic crystal structures with a central defect used to accelerate electrons and achieve high longitudinal electric fields. Extremely compact and less costly than the traditional accelerators, these structures can support higher accelerating gradients and will open a new era in high energy physics as well as other fields of science. Based on direct laser acceleration in dielectric materials, the so called photonic band gap accelerators will benefit from mature laser and semiconductor industries. One of the key elements to direct laser acceleration in hollow core PCFs, is maintaining thermal and structural stability. Previous simulations demonstrate that accelerating modes are sensitive to the geometry of the defect region and the variations in the effective index. Unlike the telecom modes (for which over 95% of the energy propagates in the hollow core) most of the power of these modes is located in the glass at the periphery of the central hole which has a higher thermal constant than air (γSiO#sub 2# = 1.19 x 10-6 1/K, γair = -9 x 10-7 1/K with γ = dn/dT). To fully control laser driven acceleration, we need to evaluate the thermal and structural consequences of such modes on the PCFs. We are conducting series of interferometric tests to quantify the dependencies of the HC-633-02 (NKT Photonics) propagation constant (kz) on temperature, vibration amplitude, stress and electric field strength. In this paper we will present the theoretical principles characterizing the thermal behavior of a PCF, the measurements realized for the fundamental telecom mode (TE00), and the experimental demonstration of TM-like mode propagation in the HC-633-02 fiber.

  6. Diversity and characterization of polymorphic 5' promoter haplotypes of MICA and MICB genes.

    Science.gov (United States)

    Cox, S T; Madrigal, J A; Saudemont, A

    2014-09-01

    The major histocompatibility complex (MHC) class I-related chain A (MICA) and B (MICB) are ligands for the natural killer group 2, member D (NKG2D) activating receptor expressed on natural killer (NK) cells, natural killer T (NKT) cells, CD8+ T cells and γδ T cells. Natural killer group 2, member D (NKG2D) ligand expression is stress-related and upregulated by infected or oncogenic cells leading to cytolysis. MICA and MICB genes display considerable polymorphism among individuals and studies have investigated allelic association with disease and relevance of MICA in transplantation, with variable success. It is now known that promoters of MICA and MICB are polymorphic with some polymorphisms associating with reduced expression. We sequenced International Histocompatibility Workshop (IHW) cell line DNA to determine promoter types and alleles encoded by exons 2-6. We found 8 of 12 known MICA promoter polymorphisms and although promoter P7 dominated, other promoters associated with the same allele. For example, MICA*002:01 had promoters P3, P4 or P7 and the common MICA*008:01/04 type had P1, P6 or P7. Similarly, we sequenced 8 of 12 known MICB promoter haplotypes. Some coding region defined MICB alleles had a single promoter, for example, MICB*002:01 and promoter P9, whereas the promiscuous MICB*005 allele had promoters P1, P2, P5, P6, P10 or P12. The results indicate potential for variation in expression of MICA and MICB ligands between individuals with the same allelic types. If differential expression by polymorphic MICA and MICB promoters is confirmed by functional studies, involvement of these genes in disease susceptibility or adverse transplantation outcomes may require knowledge of both promoter and allelic types to make meaningful conclusions.

  7. IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis.

    Directory of Open Access Journals (Sweden)

    Paméla Gasse

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice. METHODS: The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice. RESULTS: We show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+ γδ T cells and to a lesser extent by CD4αβ(+ T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis. CONCLUSIONS: Our findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology.

  8. Kontrazeption und Schwangerschaft bei Frauen mit Epilepsie - Eine Stellungnahme der DGGEF

    Directory of Open Access Journals (Sweden)

    Rabe T

    2010-01-01

    Full Text Available Epilepsien gehören zu den häufigsten neurologischen Erkrankungen. Für Frauen, die unter einer Epilepsie leiden, ist eine enge Zusammenarbeit zwischen dem betreuenden Neurologen und Gynäkologen unerlässlich, da sowohl die Epilepsie an sich aber auch die antiepileptische Medikation viele Bereiche des Lebens der betroffenen Frauen negativ beeinflussen kann: so können Fertilität und reproduktive Funktionen eingeschränkt sein, aber auch die bidirektionalen Interaktionen zwischen der antiepileptischen Therapie und hormonalen Kontrazeptiva müssen berücksichtigt werden, um ungeplante Schwangerschaften und eine Verschlechterung der Anfallskontrolle zu verhindern. Das mit einer antiepileptischen Therapie assoziierte teratogene Risiko muss, ebenso wie das mit der Behandlung möglicherweise verbundene Risiko einer ungünstigen Beeinflussung der kognitiven Entwicklung beim Kind, gegenüber dem Nutzen einer optimalen Anfallskontrolle abgewogen werden. Wenn möglich, sollten Frauen im reproduktionsfähigen Alter auf ein wenig teratogenes Therapieregime eingestellt werden. Eine umfassende proaktive präkonzeptionelle Beratung ist bei Frauen mit Epilepsie obligat, um bei Mutter und Kind einen möglichst unproblematischen Verlauf von Schwangerschaft, Geburt und Postpartalzeit zu ermöglichen. Im Allgemeinen wird bei Frauen mit Epilepsie eine hochdosierte, bereits präkonzeptionell zu beginnende Folsäureprophylaxe angeraten, um das Risiko für das Auftreten großer Fehlbildungen zu reduzieren. Im Verlauf der Schwangerschaft können je nach antiepileptischer Therapie eine regelmäßige Überprüfung der Antieepileptikaspiegel und ggf. auch eine Anpassung der Dosierung notwendig werden. Eine differenzierte Fehlbildungsdiagnostik sollte genauso wie die regelmäßige Überwachung der Schwangerschaft auf geburtshilfliche Komplikationen Teil der Routineversorgung von Frauen mit Epilepsie sein.

  9. The immune-body cytokine network defines a social architecture of cell interactions

    Directory of Open Access Journals (Sweden)

    Alon Uri

    2006-10-01

    Full Text Available Abstract Background Three networks of intercellular communication can be associated with cytokine secretion; one limited to cells of the immune system (immune cells, one limited to parenchymal cells of organs and tissues (body cells, and one involving interactions between immune and body cells (immune-body interface. These cytokine connections determine the inflammatory response to injury and subsequent healing as well as the biologic consequences of the adaptive immune response to antigens. We informatically probed the cytokine database to uncover the underlying network architecture of the three networks. Results We now report that the three cytokine networks are among the densest of complex networks yet studied, and each features a characteristic profile of specific three-cell motifs. Some legitimate cytokine connections are shunned (anti-motifs. Certain immune cells can be paired by their input-output positions in a cytokine architecture tree of five tiers: macrophages (MΦ and B cells (BC comprise the first tier; the second tier is formed by T helper 1 (Th1 and T helper 2 (Th2 cells; the third tier includes dendritic cells (DC, mast cells (MAST, Natural Killer T cells (NK-T and others; the fourth tier is formed by neutrophils (NEUT and Natural Killer cells (NK; and the Cytotoxic T cell (CTL stand alone as a fifth tier. The three-cell cytokine motif architecture of immune system cells places the immune system in a super-family that includes social networks and the World Wide Web. Body cells are less clearly stratified, although cells involved in wound healing and angiogenesis are most highly interconnected with immune cells. Conclusion Cytokine network architecture creates an innate cell-communication platform that organizes the biologic outcome of antigen recognition and inflammation. Informatics sheds new light on immune-body systems organization. Reviewers This article was reviewed by Neil Greenspan, Matthias von Herrath and Anne Cooke.

  10. Protective and Pathogenic Roles of CD8+ T Lymphocytes in Murine Orientia tsutsugamushi Infection

    Science.gov (United States)

    Hauptmann, Matthias; Kolbaum, Julia; Lilla, Stefanie; Wozniak, David; Gharaibeh, Mohammad; Fleischer, Bernhard; Keller, Christian A.

    2016-01-01

    T cells are known to contribute to immune protection against scrub typhus, a potentially fatal infection caused by the obligate intracellular bacterium Orientia (O.) tsutsugamushi. However, the contribution of CD8+ T cells to protection and pathogenesis during O. tsutsugamushi infection is still unknown. Using our recently developed BALB/c mouse model that is based on footpad inoculation of the human-pathogenic Karp strain, we show that activated CD8+ T cells infiltrate spleen and lung during the third week of infection. Depletion of CD8+ T cells with monoclonal antibodies resulted in uncontrolled pathogen growth and mortality. Adoptive transfer of CD8+ T cells from infected animals protected naïve BALB/c mice from lethal outcome of intraperitoneal challenge. In C57Bl/6 mice, the pulmonary lymphocyte compartment showed an increased percentage of CD8+ T cells for at least 135 days post O. tsutsugamushi infection. Depletion of CD8+ T cells at 84 days post infection caused reactivation of bacterial growth. In CD8+ T cell-deficient beta 2-microglobulin knockout mice, bacterial replication was uncontrolled, and all mice succumbed to the infection, despite higher serum IFN-γ levels and stronger macrophage responses in liver and lung. Moreover, we show that CD8+ T cells but not NKT cells were required for hepatocyte injury: elevated concentrations of serum alanine aminotransferase and infection-induced subcapsular necrotic liver lesions surrounded by macrophages were found in C57Bl/6 and CD1d-deficient mice, but not in beta 2-microglobulin knockout mice. In the lungs, peribronchial macrophage infiltrations also depended on CD8+ T cells. In summary, our results demonstrate that CD8+ T cells restrict growth of O. tsutsugamushi during acute and persistent infection, and are required to protect from lethal infections in BALB/c and C57BL/6 mice. However, they also elicit specific pathologic tissue lesions in liver and lung. PMID:27606708

  11. Malignant lymphoma

    International Nuclear Information System (INIS)

    This paper describes the background and treatment, especially focusing on radiotherapy (RT), of stage I-II malignant lymphoma (ML) occurring in head and neck. For diffuse large B-cell lymphoma, the most frequently occurring ML in Japan (about 40% of all MLs), the current standard protocol involves 3 cycles of chemotherapy (CT) like rituximab to cyclophosphamide/doxorubicin/vincristine/predonisolone (CHOP) regimen followed by RT. Authors use the dose around 30 Gy/15 fr for CR patients after CHOP and 40-50 Gy/20-25 fr for PR ones. Recurrence scarcely occurs in the RT target region. However, significance of RT is still somehow controversial in this ML and addition of CHOP is currently noted. Mucosa-associated lymphoid tissue lymphoma (8.45% of Japanese ML) occurs mainly in glands and orbit and may be related with Chlamydia infection. RT is usually conducted to the whole organ with lesion as the clinical target with fractionated 30 Gy. Nasal NK/T cell lymphoma (2.6%), possibly associated with Epstein-Barr (EB) virus, is usually resistant to CHOP. Recommended is CT after RT with the dose of 50-54 Gy and depending on the target site, advanced RT like intensity-modified one is desirable. Hodgkin lymphoma (about 5%) occurs in lymph node and is derived from B-lymphocyte. Irradiation field involves the region of the disease node or that additionally including its neighbors and doses of about 20 Gy and 30 Gy are given in child and adult patients, respectively. For follicular and other tissue type lymphomas, noted are novel therapies like rituximab-combined CT, immuno-RT with 90Y-ibritumomab and 131I-tositumomab. Recently, positron emission tomography (PET) is essential for treatment assessment of the clinical response of ML in the guideline. (R.T.)

  12. Persistent changes in circulating and intestinal γδ T cell subsets, invariant natural killer T cells and mucosal-associated invariant T cells in children and adults with coeliac disease.

    Directory of Open Access Journals (Sweden)

    Margaret R Dunne

    Full Text Available Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets, natural killer cells, CD56(+ T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

  13. mRNA-based vaccines synergize with radiation therapy to eradicate established tumors

    International Nuclear Information System (INIS)

    The eradication of large, established tumors by active immunotherapy is a major challenge because of the numerous cancer evasion mechanisms that exist. This study aimed to establish a novel combination therapy consisting of messenger RNA (mRNA)-based cancer vaccines and radiation, which would facilitate the effective treatment of established tumors with aggressive growth kinetics. The combination of a tumor-specific mRNA-based vaccination with radiation was tested in two syngeneic tumor models, a highly immunogenic E.G7-OVA and a low immunogenic Lewis lung cancer (LLC). The molecular mechanism induced by the combination therapy was evaluated via gene expression arrays as well as flow cytometry analyses of tumor infiltrating cells. In both tumor models we demonstrated that a combination of mRNA-based immunotherapy with radiation results in a strong synergistic anti-tumor effect. This was manifested as either complete tumor eradication or delay in tumor growth. Gene expression analysis of mouse tumors revealed a variety of substantial changes at the tumor site following radiation. Genes associated with antigen presentation, infiltration of immune cells, adhesion, and activation of the innate immune system were upregulated. A combination of radiation and immunotherapy induced significant downregulation of tumor associated factors and upregulation of tumor suppressors. Moreover, combination therapy significantly increased CD4+, CD8+ and NKT cell infiltration of mouse tumors. Our data provide a scientific rationale for combining immunotherapy with radiation and provide a basis for the development of more potent anti-cancer therapies. The online version of this article (doi:10.1186/1748-717X-9-180) contains supplementary material, which is available to authorized users

  14. Patterns of early gut colonization shape future immune responses of the host.

    Directory of Open Access Journals (Sweden)

    Camilla Hartmann Friis Hansen

    Full Text Available The most important trigger for immune system development is the exposure to microbial components immediately after birth. Moreover, targeted manipulation of the microbiota can be used to change host susceptibility to immune-mediated diseases. Our aim was to analyze how differences in early gut colonization patterns change the composition of the resident microbiota and future immune system reactivity. Germ-free (GF mice were either inoculated by single oral gavage of caecal content or let colonized by co-housing with specific pathogen-free (SPF mice at different time points in the postnatal period. The microbiota composition was analyzed by denaturing gradient gel electrophoresis for 16S rRNA gene followed by principal component analysis. Furthermore, immune functions and cytokine concentrations were analyzed using flow cytometry, ELISA or multiplex bead assay. We found that a single oral inoculation of GF mice at three weeks of age permanently changed the gut microbiota composition, which was not possible to achieve at one week of age. Interestingly, the ex-GF mice inoculated at three weeks of age were also the only mice with an increased pro-inflammatory immune response. In contrast, the composition of the gut microbiota of ex-GF mice that were co-housed with SPF mice at different time points was similar to the gut microbiota in the barrier maintained SPF mice. The existence of a short GF postnatal period permanently changed levels of systemic regulatory T cells, NK and NKT cells, and cytokine production. In conclusion, a time window exists that enables the artificial colonization of GF mice by a single oral dose of caecal content, which may modify the future immune phenotype of the host. Moreover, delayed microbial colonization of the gut causes permanent changes in the immune system.

  15. IL-33-driven ILC2/eosinophil axis in fat is induced by sympathetic tone and suppressed by obesity.

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    Ding, Xiaofeng; Luo, Yan; Zhang, Xing; Zheng, Handong; Yang, Xin; Yang, Xuexian; Liu, Meilian

    2016-10-01

    Group 2 innate lymphoid cells (ILC2s) in white adipose tissue (WAT) promote WAT browning and assist in preventing the development of obesity. However, how ILC2 in adipose tissue is regulated remains largely unknown. Here, our study shows that ILC2s are present in brown adipose tissue (BAT) as well as subcutaneous and epididymal WAT (sWAT and eWAT). The fractions of ILC2s, natural killer T (NKT) cells and eosinophils in sWAT, eWAT and BAT are significantly decreased by high-fat-diet (HFD) feeding and leptin deficiency-induced obesity. Consistent with this, the adipose expression and circulating levels of IL-33, a key inducing cytokine of ILC2, are significantly downregulated by obesity. Furthermore, administration of IL-33 markedly increases the fraction of ILC2 and eosinophil as well as the expression of UCP1 and tyrosine hydroxylase (TH), a rate-limiting enzyme in catecholamine biosynthesis, in adipose tissue of HFD-fed mice. On the other hand, cold exposure induces the expression levels of IL-33 and UCP1 and the population of ILC2 and eosinophil in sWAT, and these promoting effects of cold stress are reversed by neutralization of IL-33 signaling in vivo Moreover, the basal and cold-induced IL-33 and ILC2/eosinophil pathways are significantly suppressed by sympathetic denervation via local injection of 6-hydroxydopamine (6-OHDA) in sWAT. Taken together, our data suggest that the ILC2/eosinophil axis in adipose tissue is regulated by sympathetic nervous system and obesity in IL-33-dependent manner, and IL-33-driven ILC2/eosinophil axis is implicated in the development of obesity. PMID:27562191

  16. Fine Mapping and Functional Analysis of the Multiple Sclerosis Risk Gene CD6

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    Swaminathan, Bhairavi; Cuapio, Angélica; Alloza, Iraide; Matesanz, Fuencisla; Alcina, Antonio; García-Barcina, Maria; Fedetz, Maria; Fernández, Óscar; Lucas, Miguel; Órpez, Teresa; Pinto-Medel, Mª Jesus; Otaegui, David; Olascoaga, Javier; Urcelay, Elena; Ortiz, Miguel A.; Arroyo, Rafael; Oksenberg, Jorge R.; Antigüedad, Alfredo; Tolosa, Eva; Vandenbroeck, Koen

    2013-01-01

    CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2nd SRCR domain with susceptibility to MS (Pmax(T) permutation = 1×10−4). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4+ naïve cells, P = 0.0001; CD8+ naïve cells, P<0.0001; CD4+ and CD8+ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4+ and CD8+ T cells. PMID:23638056

  17. Derangements of liver tissue bioenergetics in Concanavalin A-induced hepatitis

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    Al-Shamsi Mariam

    2013-01-01

    Full Text Available Abstract Background A novel in vitro system was employed to investigate liver tissue respiration (mitochondrial O2 consumption in mice treated with concanavalin A (Con A. This study aimed to investigate hepatocyte bioenergetics in this well-studied hepatitis model. Methods C57Bl/6 and C57Bl/6 IFN-γ−/− mice were injected intravenously with 12 mg ConA/kg. Liver specimens were collected at various timepoints after injection and analyzed for cellular respiration and caspase activation. Serum was analyzed for interferon-gamma (IFN-γ and aminotransferases. Fluorescence activated cell sorting analysis was used to determine the phenotype of infiltrating cells, and light and electron microscopy were used to monitor morphological changes. Phosphorescence analyzer that measured dissolved O2 as function of time was used to evaluate respiration. Results In sealed vials, O2 concentrations in solutions containing liver specimen and glucose declined linearly with time, confirming zero-order kinetics of hepatocyte respiration. O2 consumption was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. Enhanced liver respiration (by ≈68%, pp=0.005 was noted 12 hr after ConA treatment, and occurred in conjunction with deranged mitochondria, areas of necrosis, and prominent infiltrations with immune cells, most significantly, CD3+NKT+ cells. Increases in intracellular caspase activity and serum IFN-γ and aminotransferase levels were noted 3 hr after ConA treatment and progressed with time. The above-noted changes were less pronounced in C57Bl/6 IFN-γ−/− mice treated with ConA. Conclusions Based on these results, liver tissue bioenergetics is increased 3 hr after ConA exposure. This effect is driven by the pathogenesis of the disease, in which IFN-γ and other cytokines contribute to. Subsequent declines in liver bioenergetics appear to be a result of necrosis and active caspases targeting the mitochondria within hepatocytes.

  18. ESWL aus der Sicht des Osteologen

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    Tischer T

    2004-01-01

    Full Text Available In der Urologie hat die Zertrümmerung von schmerzhaften Nierensteinen mittels extrakorporaler Stoßwellen die nicht-invasive Therapie von Nierensteinen revolutioniert. Dieses erfolgversprechende Konzept wurde vor über 15 Jahren in der Orthopädie aufgegriffen. Dabei wurde versucht, die verzögerte Knochenbruchheilung durch Stimulation der Knochenenden mit Hilfe fokussierter extrakorporaler Stoßwellen zu beschleunigen. Im folgenden wurde dieses Verfahren erfolgreich zur Behandlung von Knochenbruchheilungsstörungen, der Tendinitis calcarea, der Epicondylitis radialis humeri und der Fasciitis plantaris eingesetzt. Dabei ist – anders als bei der Nierensteinzertrümmerung – nicht die Zerstörung von Hartgewebe für den Wirkmechanismus verantwortlich. Lange Zeit waren die Kenntnisse sowohl über die Wirkmechanismen extrakorporaler Stoßwellen am Knochen, als auch über mögliche unerwünschte Nebenwirkungen nur eingeschränkt verfügbar. In den letzten Jahren sind jedoch viele neue Studien publiziert worden. Die vorliegende Arbeit faßt den entsprechenden gegenwärtigen Kenntnisstand über die Wirkung extrakorporaler Stoßwellen auf den Knochen aus tier- und zellkulturexperimentellen Grundlagenuntersuchungen zusammen. Insbesondere in bezug auf mögliche unerwünschte Nebenwirkungen der ESWT haben die bisher durchgeführten Untersuchungen wertvolle Hinweise ergeben. Darüber hinaus konnten in jüngster Zeit erste Ergebnisse bezüglich der molekularen Wirkweise extrakorporaler Stoßwellen am Stütz- und Bewegungsapparat vorgelegt werden, die ein komplexes Bild der tatsächlichen Vorgänge erahnen lassen. Durch eine Intensivierung der tierexperimentellen Grundlagenforschung zur ESWT wird es möglich sein, in naher Zukunft eine breit abgesicherte, experimentell-wissenschaftliche Grundlage zum Einsatz extrakorporaler Stoßwellen am Stütz- und Bewegungsapparat zu erarbeiten.

  19. Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth

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    Roland El Ghazal

    2016-05-01

    Full Text Available In cancer, proteoglycans have been found to play roles in facilitating the actions of growth factors, and effecting matrix invasion and remodeling. However, little is known regarding the genetic and functional importance of glycan chains displayed by proteoglycans on dendritic cells (DCs in cancer immunity. In lung carcinoma, among other solid tumors, tumor-associated DCs play largely subversive/suppressive roles, promoting tumor growth and progression. Herein, we show that targeting of DC glycan sulfation through mutation in the heparan sulfate biosynthetic enzyme N-deacetylase/N-sulfotransferase-1 (Ndst1 in mice increased DC maturation and inhibited trafficking of DCs to draining lymph nodes. Lymphatic-driven DC migration and chemokine (CCL21-dependent activation of a major signaling pathway required for DC migration (as measured by phospho-Akt were sensitive to Ndst1 mutation in DCs. Lewis lung carcinoma tumors in mice deficient in Ndst1 were reduced in size. Purified CD11c+ cells from the tumors, which contain the tumor-infiltrating DC population, showed a similar phenotype in mutant cells. These features were replicated in mice deficient in syndecan-4, the major heparan sulfate proteoglycan expressed on the DC surface: Tumors were growth-impaired in syndecan-4–deficient mice and were characterized by increased infiltration by mature DCs. Tumors on the mutant background also showed greater infiltration by NK cells and NKT cells. These findings indicate the genetic importance of DC heparan sulfate proteoglycans in tumor growth and may guide therapeutic development of novel strategies to target syndecan-4 and heparan sulfate in cancer.

  20. Glycan Sulfation Modulates Dendritic Cell Biology and Tumor Growth.

    Science.gov (United States)

    El Ghazal, Roland; Yin, Xin; Johns, Scott C; Swanson, Lee; Macal, Monica; Ghosh, Pradipta; Zuniga, Elina I; Fuster, Mark M

    2016-05-01

    In cancer, proteoglycans have been found to play roles in facilitating the actions of growth factors, and effecting matrix invasion and remodeling. However, little is known regarding the genetic and functional importance of glycan chains displayed by proteoglycans on dendritic cells (DCs) in cancer immunity. In lung carcinoma, among other solid tumors, tumor-associated DCs play largely subversive/suppressive roles, promoting tumor growth and progression. Herein, we show that targeting of DC glycan sulfation through mutation in the heparan sulfate biosynthetic enzyme N-deacetylase/N-sulfotransferase-1 (Ndst1) in mice increased DC maturation and inhibited trafficking of DCs to draining lymph nodes. Lymphatic-driven DC migration and chemokine (CCL21)-dependent activation of a major signaling pathway required for DC migration (as measured by phospho-Akt) were sensitive to Ndst1 mutation in DCs. Lewis lung carcinoma tumors in mice deficient in Ndst1 were reduced in size. Purified CD11c+ cells from the tumors, which contain the tumor-infiltrating DC population, showed a similar phenotype in mutant cells. These features were replicated in mice deficient in syndecan-4, the major heparan sulfate proteoglycan expressed on the DC surface: Tumors were growth-impaired in syndecan-4-deficient mice and were characterized by increased infiltration by mature DCs. Tumors on the mutant background also showed greater infiltration by NK cells and NKT cells. These findings indicate the genetic importance of DC heparan sulfate proteoglycans in tumor growth and may guide therapeutic development of novel strategies to target syndecan-4 and heparan sulfate in cancer.