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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 of the...... mixture of sulfatide isoforms, i.e. sulfatide molecules with different long-chain bases and fatty acid chain lengths and saturation. Here, we demonstrate that sulfatide-specific CD1d-restricted murine NKT hybridomas recognized several different sulfatide isoforms. These included the physiologically...... long fatty acid (C24:0), resulted in reduced stimulatory capacity, and fatty acid hydroxylation abolished the response. Moreover, sulfatide was not responsible for the natural autoreactivity toward splenocytes by XV19 T hybridoma cells. Our results reveal a promiscuity in the recognition of sulfatide...

  2. 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.

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

    Science.gov (United States)

    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

  4. Activation of Nonclassical CD1d-Restricted NK T Cells Induces Airway Hyperreactivity in β2-Microglobulin-Deficient Mice1

    Science.gov (United States)

    Meyer, Everett H.; Pichavant, Muriel; Akbari, Omid; Yasumi, Takahiro; Savage, Paul B.; DeKruyff, Rosemarie H.; Umetsu, Dale T.

    2016-01-01

    Allergic asthma is characterized by Th2-driven eosinophilic airway inflammation and by a central feature called airway hyperreactivity (AHR), development of which requires the presence of classical type I invariant NK T (iNKT) cells. Allergen-induced AHR, however, develops in β2-microglobulin (β2m)−/− mice, which lack classical iNKT cells, suggesting that in some situations iNKT cells may be dispensable for the development of AHR. In contrast, our studies now suggest that a CD1d-restricted, NK1.1+ noninvariant TCR NKT cell population is present in β2m−/− mice and is responsible for the development of AHR but not for Th2 responses. Furthermore, treatment of β2m−/− mice with anti-CD1d mAb or anti-NK1.1 mAb unexpectedly abolished allergen-induced AHR. The CD1-restricted NKT cells in these mice, which failed to respond to α-galactosylceramide and which therefore were not classical type I iNKT cells, appear to represent an NKT cell subset restricted by a β2m-independent form of CD1d. These results indicate that, although classical type I iNKT cells are normally required for the development of AHR, under different circumstances other NKT cell subsets, including nonclassical NKT cells, may substitute for classical iNKT cells and induce AHR. PMID:18802058

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

    Science.gov (United States)

    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

  6. 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...

  7. 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

    exhibited a memory phenotype including high ICOS expression, increased cytokine production, and limited display of NK cell markers, compared with double-negative 24aß NKT cells. Blocking of ICOS or the programmed death-1/programmed death ligand 1 pathway was shown to abolish the regulation that occurred......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...

  8. Natural killer T (NKT)–B-cell interactions promote prolonged antibody responses and long-term memory to pneumococcal capsular polysaccharides

    OpenAIRE

    Bai, Li; Deng, Shenglou; Reboulet, Rachel; Mathew, Rebecca; Teyton, Luc; Savage, Paul B.; Bendelac, Albert

    2013-01-01

    Antibodies directed against microbial polysaccharides are a critical component of protective immune responses and vaccines. We used nanoparticles coexpressing pneumococcal capsular polysaccharides and a cell wall lipid antigen analog to model NKT–B-cell interactions. Our study demonstrated CD1d-restricted cognate interactions, isotype switch, affinity maturation, and long-term memory, despite the apparent failure of NKT cells to differentiate into follicular helper cells. The findings demonst...

  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. 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...

  11. 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...

  12. iNKT-cell help to B cells: a cooperative job between innate and adaptive immune responses.

    Science.gov (United States)

    Dellabona, Paolo; Abrignani, Sergio; Casorati, Giulia

    2014-08-01

    T-cell help to B lymphocytes is one of the most important events in adaptive immune responses in health and disease. It is generally delivered by cognate CD4(+) T follicular helper (T(FH)) cells via both cell-to-cell contacts and soluble mediators, and it is essential for both the clonal expansion of antibody (Ab)-secreting B cells and memory B-cell formation. CD1d-restricted invariant natural killer T (iNKT) cells are a subset of innate-like T lymphocytes that rapidly respond to stimulation with specific lipid antigens (Ags) that are derived from infectious pathogens or stressed host cells. Activated iNKT cells produce a wide range of cytokines and upregulate costimulatory molecules that can promote activation of dendritic cells (DCs), natural killer (NK) cells, and T cells. A decade ago, we discovered that iNKT cells can help B cells to proliferate and to produce IgG Abs in vitro and in vivo. This adjuvant-like function of Ag-activated iNKT cells provides a flexible set of helper mechanisms that expand the current paradigm of T-cell-B-cell interaction and highlights the potential of iNKT-cell targeting vaccine formulations. PMID:24782127

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

    Science.gov (United States)

    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

  14. 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

  15. 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.

  16. 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.

  17. [NKT cells: their development, mechanisms and effects of action].

    Science.gov (United States)

    Bojarska-Junak, Agnieszka; Tabarkiewicz, Jacek; Roliński, Jacek

    2013-01-01

    NKT cells are a heterogeneous subset of T lymphocytes that share surface markers and functional characteristics with both conventional T lymphocytes and natural killer cells. Most NKT cells express a semi-invariant T cell receptor that reacts with glycolipid antigens presented by the CD1d molecule on the surface of antigen-presenting cells. NKT cells can modulate the immune response against infectious agents, autoantigens, tumors, tissue grafts and allergens. NKT cells mediate the activities through their ability to express pro- and anti-inflammatory cytokines that influence the type and magnitude of the immune response. The manuscript summarizes current views on development of NKT cells as well as mechanisms and effects of their action.  PMID:23475484

  18. 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

  19. 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...... molecule. Genetic evidence suggested that beta-glucosylceramide derived glycosphingolipids (GSLs) are natural ligands for NKT cells. N-butyldeoxygalactonojirimycin (NB-DGJ), a drug that specifically inhibits the glucosylceramide synthase, inhibits the endogenous ligands for NKT cells. Furthermore, we and...... 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....

  20. 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...

  1. NKT cells: their development, mechanisms and effects of action 

    OpenAIRE

    Agnieszka Bojarska-Junak; Jacek Tabarkiewicz; Jacek Roliński

    2013-01-01

    NKT cells are a heterogeneous subset of T lymphocytes that share surface markers and functional characteristics with both conventional T lymphocytes and natural killer cells. Most NKT cells express a semi-invariant T cell receptor that reacts with glycolipid antigens presented by the CD1d molecule on the surface of antigen-presenting cells. NKT cells can modulate the immune response against infectious agents, autoantigens, tumors, tissue grafts and allergens. NKT cells mediate the activities ...

  2. 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

  3. Chronic alcohol consumption enhances iNKT cell maturation and activation

    International Nuclear Information System (INIS)

    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− 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+CD44hi mature iNKT cells but does not alter the number of NK1.1− immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1− iNKT cells, especially the NK1.1−CD44lo Stage I iNKT cells. The percentage of NKG2A+ iNKT cells increases in all of the tissues and organs examined; whereas CXCR3+ 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 consumption induces Th1 immune response upon iNKT cell in vivo

  4. 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

  5. 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

  6. 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.

  7. NKT cell–dependent leukemia eradication following stem cell mobilization with potent G-CSF analogs

    OpenAIRE

    Morris, Edward S.; MacDonald, Kelli P.A.; Rowe, Vanessa; Banovic, Tatjana; Kuns, Rachel D.; Don, Alistair L. J.; Bofinger, Helen M.; Burman, Angela C.; Olver, Stuart D.; Kienzle, Norbert; Porcelli, Steven A.; Pellicci, Daniel G.; Godfrey, Dale I.; Smyth, Mark J; Hill, Geoffrey R.

    2005-01-01

    NKT cells have pivotal roles in immune regulation and tumor immunosurveillance. We report that the G-CSF and FMS-like tyrosine kinase 3 ligand (Flt-3L) chimeric cytokine, progenipoietin-1, markedly expands the splenic and hepatic NKT cell population and enhances functional responses to α-galactosylceramide. In a murine model of allogeneic stem cell transplantation, donor NKT cells promoted host DC activation and enhanced perforin-restricted CD8+ T cell cytotoxicity against host-type antigens....

  8. Invariant NKT Cell Response to Dengue Virus Infection in Human

    OpenAIRE

    Matangkasombut, Ponpan; Chan-in, Wilawan; Opasawaschai, Anunya; Pongchaikul, Pisut; Tangthawornchaikul, Nattaya; Vasanawathana, Sirijitt; Limpitikul, Wannee; Malasit, Prida; Duangchinda, Thaneeya; Screaton, Gavin; Mongkolsapaya, Juthathip

    2014-01-01

    Background Dengue viral infection is a global health threat without vaccine or specific treatment. The clinical outcome varies from asymptomatic, mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF). While adaptive immune responses were found to be detrimental in the dengue pathogenesis, the roles of earlier innate events remain largely uninvestigated. Invariant natural killer T (iNKT) cells represent innate-like T cells that could dictate subsequent adaptive response but their rol...

  9. 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

  10. Invariant NKT Cell Defects in Vitamin D Receptor Knockout Mice Prevents Experimental Lung Inflammation

    OpenAIRE

    Yu, Sanhong; Zhao, Jun; Cantorna, Margherita T.

    2011-01-01

    Vitamin D receptor (VDR) deficiency (knockout, KO) results in a failure of mice to generate an airway hyper-reactivity (AHR) response on both the Balb/c and C57BL/6 background. The cause of the failed AHR response is the defective population of iNKT cells in the VDR KO mice since wildtype (WT) iNKT cells rescued the AHR response. VDR KO mice had significantly fewer iNKT cells and normal numbers of T cells in the spleen compared to WT mice. In Balb/c VDR KO mice the reduced frequencies of iNKT...

  11. 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.

  12. NKT cells: their development, mechanisms and effects of action 

    Directory of Open Access Journals (Sweden)

    Agnieszka Bojarska-Junak

    2013-02-01

    Full Text Available NKT cells are a heterogeneous subset of T lymphocytes that share surface markers and functional characteristics with both conventional T lymphocytes and natural killer cells. Most NKT cells express a semi-invariant T cell receptor that reacts with glycolipid antigens presented by the CD1d molecule on the surface of antigen-presenting cells. NKT cells can modulate the immune response against infectious agents, autoantigens, tumors, tissue grafts and allergens. NKT cells mediate the activities through their ability to express pro- and anti-inflammatory cytokines that influence the type and magnitude of the immune response. The manuscript summarizes current views on development of NKT cells as well as mechanisms and effects of their action. 

  13. 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.

  14. 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.

  15. Inhibitory function of NKT cells during early induction phase of nickel allergy.

    Science.gov (United States)

    Okuno, Hironori; Satoh, Masashi; Takeuchi, Emiko; Eshima, Koji; Terashima, Masazumi; Komotori, Jun; Habu, Sonoko; Tamauchi, Hidekazu; Iwabuchi, Kazuya

    2016-07-01

    Until now, metal allergies have been regarded as a Th1-type immune response. However, because the contribution of a Th2-type immune response has been suggested by clinical findings, we previously examined the Th2-type immune response during the development of metal allergies using a GATA-3 transgenic (GATA-3 Tg) mouse model. As a result, a Th2-type immunization reaction was suggested to be involved in the early phase of metal allergies. Recently, the involvement of NKT cells in metal allergies has been suggested. We examined this possibility using the activation of NKT cells and an NKT cell-deficient mouse model to determine the contribution of NKT cells to nickel allergy in the present study. In NKT cell-deficient mice, ear swelling was remarkably increased, compared with that in control mice. Also, in mice that had been treated with α-galactosylceramide (α-GalCer) to activate NKT cells, the ear swelling response was remarkably inhibited, compared with that in untreated mice. These facts show that NKT cells are involved in the inhibition of nickel allergy-induced ear swelling responses. PMID:26868431

  16. 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

  17. NKT cells prevent chronic joint inflammation after infection with Borrelia burgdorferi.

    Science.gov (United States)

    Tupin, Emmanuel; Benhnia, Mohammed Rafii-El-Idrissi; Kinjo, Yuki; Patsey, Rebeca; Lena, Christopher J; Haller, Matthew C; Caimano, Melissa J; Imamura, Masakazu; Wong, Chi-Huey; Crotty, Shane; Radolf, Justin D; Sellati, Timothy J; Kronenberg, Mitchell

    2008-12-16

    Borrelia burgdorferi is the etiologic agent of Lyme disease, a multisystem inflammatory disorder that principally targets the skin, joints, heart, and nervous system. The role of T lymphocytes in the development of chronic inflammation resulting from B. burgdorferi infection has been controversial. We previously showed that natural killer T (NKT) cells with an invariant (i) TCR alpha chain (iNKT cells) recognize glycolipids from B. burgdorferi, but did not establish an in vivo role for iNKT cells in Lyme disease pathogenesis. Here, we evaluate the importance of iNKT cells for host defense against these pathogenic spirochetes by using Valpha14i NKT cell-deficient (Jalpha18(-/-)) BALB/c mice. On tick inoculation with B. burgdorferi, Jalpha18(-/-) mice exhibited more severe and prolonged arthritis as well as a reduced ability to clear spirochetes from infected tissues. Valpha14i NKT cell deficiency also resulted in increased production of antibodies directed against both B. burgdorferi protein antigens and borrelial diacylglycerols; the latter finding demonstrates that anti-glycolipid antibody production does not require cognate help from Valpha14i NKT cells. Valpha14i NKT cells in infected wild-type mice expressed surface activation markers and produced IFNgamma in vivo after infection, suggesting a participatory role for this unique population in cellular immunity. Our data are consistent with the hypothesis that the antigen-specific activation of Valpha14i NKT cells is important for the prevention of persistent joint inflammation and spirochete clearance, and they counter the long-standing notion that humoral rather than cellular immunity is sufficient to facilitate Lyme disease resolution. PMID:19060201

  18. 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...

  19. 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

  20. 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.

  1. 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

  2. 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...

  3. 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

  4. 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.

  5. 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

  6. 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.

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

    DEFF Research Database (Denmark)

    Navikas, Shohreh

    2011-01-01

    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...... 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....

  8. NKT cells are necessary for maximal expression of allergic conjunctivitis1

    OpenAIRE

    Reyes, Nancy J.; Mayhew, Elizabeth; Chen, Peter W.; Niederkorn, Jerry Y.

    2010-01-01

    Allergic conjunctivitis (AC) is elicited by immediate hypersensitivity responses to environmental agents. It is initiated by a Th2-dominated immune response that is characterized by production of IgE antibodies and eosinophilic infiltration. By using an experimental mouse model of AC induced by short ragweed (SRW) pollen, we show that sensitized Jα18−/− mice, which lack type I NKT cells, and CD1d−/− mice, which lack type I and type II NKT cells, exhibited a decrease in tearing, lid edema, con...

  9. On/off TLR segnaling decides immunogenic or tolerogenic dendritic cell maturation upon NKT cell contact

    OpenAIRE

    Caielli,

    2009-01-01

    Invariant Natural Killer (iNK)T cells play opposite immune functions. They participate in the innate immune response to promote anti-microbial and anti-tumor immunity and they are crucial to maintain T cell tolerance and prevent autoimmune diseases. While it is well known that the adjuvant function of iNKT cells is mediated through maturation of dendritic cells (DC), the mechanism underlying the tolerogenic function of iNKT cells remains unclear. We performed co-culture experiments with immat...

  10. 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.

  11. Altered distribution of NK and NKT cells in follicular fluid is associated with IVF outcome

    Czech Academy of Sciences Publication Activity Database

    Křižan, Jiří; Cuchalová, Lucie; Šíma, Petr; Králíčková, M.; Madar, J.; Větvička, V.

    2009-01-01

    Roč. 82, - (2009), s. 84-88. ISSN 0165-0378 R&D Projects: GA MZd NR9135 Institutional research plan: CEZ:AV0Z50200510 Keywords : nk * nkt * follicular fluid Subject RIV: EE - Microbiology, Virology Impact factor: 2.519, year: 2009

  12. 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.

  13. 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.

  14. BAFF- and APRIL-dependent maintenance of Ab titers after immunization with T-dependent Ag and CD1d-binding ligand

    OpenAIRE

    Shah, Hemangi B.; Joshi, Sunil K.; Rampuria, Pragya; Devera, T. Scott; Lang, Gillian A.; Stohl, William; Lang, Mark L.

    2013-01-01

    CD1d-restricted invariant Natural Killer T (iNKT) cells boost humoral immunity to T-dependent Ags that are co-administered with the CD1d-binding glycolipid Ag α-galactosylceramide (α-GC). Observations that mice lacking iNKT cells have decaying Ab responses following vaccination has led to the hypothesis that iNKT cells express plasma cell (PC) survival factors that sustain specific Ab titers. Bone marrow (BM) chimeric mice in which the entire hematopoetic compartment or iNKT cells selectively...

  15. 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 ...

  16. 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...

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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...

  5. 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.

  6. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Kitayama, Shuichi; Zhang, Rong; Liu, Tian-Yi; Ueda, Norihiro; Iriguchi, Shoichi; Yasui, Yutaka; Kawai, Yohei; Tatsumi, Minako; Hirai, Norihito; Mizoro, Yasutaka; Iwama, Tatsuaki; Watanabe, Akira; Nakanishi, Mahito; Kuzushima, Kiyotaka; Uemura, Yasushi; Kaneko, Shin

    2016-01-01

    Summary 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. PMID:26862702

  9. 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 ...

  10. 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...

  11. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Invariant NKT cells are resistant to circulating CD15(+) myeloid-derived suppressor cells in patients with head and neck cancer.

    Science.gov (United States)

    Horinaka, Atsushi; Sakurai, Daiju; Ihara, Fumie; Makita, Yuji; Kunii, Naoki; Motohashi, Shinichiro; Nakayama, Toshinori; Okamoto, Yoshitaka

    2016-03-01

    Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature and progenitor myeloid cells with an immunosuppressive role in various types of cancer, including head and neck squamous cell carcinoma (HNSCC). However, the effect on the host immune system, especially on invariant NKT (iNKT) cells with potent anti-tumor activity, remains unclear. In this study, we investigated the effects of circulating MDSC subsets on the peripheral lymphocytes of patients with head and neck tumors. A significant accumulation of CD15(+) granulocytic MDSC (G-MDSC) and CD14(+) monocytic MDSC (M-MDSC) was demonstrated in HNSCC patients. The percentage of G-MDSC showed an inverse correlation with the percentage of T cells in the peripheral blood. The increased G-MDSC was significantly associated with advanced clinical stage and poor prognosis of HNSCC patients. The proliferation and viability of T cells were suppressed by CD15(+) cells, and the suppression was reversed by adding the hydrogen peroxide scavenger catalase. However, iNKT cell activation upon α-galactosylceramide (αGalCer) stimulation was not affected by the presence or absence of CD15(+) G-MDSC. These results indicate that increased G-MDSC negatively affects peripheral T cell immunity, but not iNKT cells, in HNSCC patients, and that T cells are more sensitive to hydrogen peroxide produced by G-MDSC than iNKT cells. Cancer immunotherapy designed to enhance the antitumor activity of iNKT cells by stimulation with αGalCer may remain effective in the presence of G-MDSC. PMID:26679292

  16. A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity

    OpenAIRE

    Terashima, Asuka; Watarai, Hiroshi; Inoue, Sayo; Sekine, Etsuko; Nakagawa, Ryusuke; Hase, Koji; Iwamura, Chiaki; Nakajima, Hiroshi; Nakayama, Toshinori; Taniguchi, Masaru

    2008-01-01

    Airway hypersensitive reaction (AHR) is an animal model for asthma, which is caused or enhanced by environmental factors such as allergen exposure. However, the precise mechanisms that drive AHR remain unclear. We identified a novel subset of natural killer T (NKT) cells that expresses the interleukin 17 receptor B (IL-17RB) for IL-25 (also known as IL-17E) and is essential for the induction of AHR. IL-17RB is preferentially expressed on a fraction of CD4+ NKT cells but not on other splenic l...

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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. PMID:27016770

  4. Linfoma Extranodal de Células NK/T tipo Nasal Extranodal Nasal type NK/T-Cell Lymphoma

    OpenAIRE

    Carlos S. Chiattone

    2009-01-01

    O Linfoma Extranodal de Células NK/T tipo Nasal tem uma distribuição geográfica peculiar, ocorrendo mais frequentemente em países orientais e na população nativa de alguns países da América Central e da América do Sul. Sua localização preferencial é na cavidade nasal e nos seios paranasais, mas pode acometer outras estruturas da chamada região médio-facial. Tem um padrão de disseminação com "homing" característico, incluindo pele, testículo, SNC e trato digestivo. Este linfoma, menos frequent...

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

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    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.

  6. 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

  7. Circulating and Tumor-Infiltrating Foxp3+ Regulatory T Cell Subset in Chinese Patients with Extranodal NK/T Cell Lymphoma

    OpenAIRE

    Peng, Rou-Jun; Huang, Zhou-Feng; Zhang, Yi-Lan; Yuan, Zhong-Yu; Xia, Yi; Jiang, Wen-Qi; Zeng, Yi-Xin; Li, Jiang

    2011-01-01

    Foxp3+ regulatory T lymphocytes (Tregs) usually act as an immune suppressor and correlate with poorer survival in malignancies. This study aims to investigate the distribution and characterization of Foxp3+ subset in peripheral blood mononuclear cells (PBMCs) and tumor tissues from extranodal NK/T cell lymphoma (ENKTL). Our study showed the percentage of Foxp3+ subset from PBMC was significantly higher than that of healthy individuals (P

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Linfoma Extranodal de Células NK/T tipo Nasal Extranodal Nasal type NK/T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Carlos S. Chiattone

    2009-08-01

    Full Text Available O Linfoma Extranodal de Células NK/T tipo Nasal tem uma distribuição geográfica peculiar, ocorrendo mais frequentemente em países orientais e na população nativa de alguns países da América Central e da América do Sul. Sua localização preferencial é na cavidade nasal e nos seios paranasais, mas pode acometer outras estruturas da chamada região médio-facial. Tem um padrão de disseminação com "homing" característico, incluindo pele, testículo, SNC e trato digestivo. Este linfoma, menos frequentemente, pode acometer primariamente estas regiões. A maioria destas neoplasias apresenta um fenótipo NK, mas alguns poucos casos podem ter sua origem em células T verdadeiras, por este motivo é designado "linfoma NK/T". O genoma do vírus Epstein-Barr é detectado na maioria dos casos, sugerindo uma relação etiológica. Embora este linfoma seja sensível à radioterapia, apresenta mais frequentemente resistência a agentes quimioterápicos que outros linfomas. Uma possível explicação para a resistência é a usual expressão de glicoproteína-p. O prognóstico destes linfomas é pobre, sendo necessária a investigação de novas modalidades terapêuticas.Extranodal Nasal type NK/T-Cell Lymphoma has a peculiar geographic distribution, occurring more frequently in Eastern countries and in the native populations of some Central and South American countries. It is commonly found in the nasal cavity and paranasal sinuses, but may also compromise other structures in the mid-facial region. The disease has a characteristic homing dissemination pattern, including skin, testis, CNS and digestive tract. This lymphoma can, less frequently, primarily compromise these regions. The majority of these neoplastic diseases present an NK phenotype, but a few cases can be truly of T-cell origin, because of which it is designed "NK/T-cell lymphoma". The Epstein-Barr virus genome can be detected in most of the cases, suggesting an etiological

  10. 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.

  11. 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

  12. 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

  13. T cell factor-1 controls the lifetime of CD4+ CD8+ thymocytes in vivo and distal T cell receptor α-chain rearrangement required for NKT cell development.

    Directory of Open Access Journals (Sweden)

    Archna Sharma

    Full Text Available Natural killer T (NKT cells are a component of innate and adaptive immune systems implicated in immune, autoimmune responses and in the control of obesity and cancer. NKT cells develop from common CD4+ CD8+ double positive (DP thymocyte precursors after the rearrangement and expression of T cell receptor (TCR Vα14-Jα18 gene. Temporal regulation and late appearance of Vα14-Jα18 rearrangement in immature DP thymocytes has been demonstrated. However, the precise control of lifetime of DP thymocytes in vivo that enables distal rearrangements remains incompletely defined. Here we demonstrate that T cell factor (TCF-1, encoded by the Tcf7 gene, is critical for the extended lifetime of DP thymocytes. TCF-1-deficient DP thymocytes fail to undergo TCR Vα14-Jα18 rearrangement and produce significantly fewer NKT cells. Ectopic expression of Bcl-xL permits Vα14-Jα18 rearrangement and rescues NKT cell development. We report that TCF-1 regulates expression of RORγt, which regulates DP thymocyte survival by controlling expression of Bcl-xL. We posit that TCF-1 along with its cofactors controls the lifetime of DP thymocytes in vivo.

  14. 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.

  15. 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...

  16. 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

  17. 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

  18. 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...

  19. Nasal NK/T cell lymphoma presents with long-term nasal blockage and fever: a rare case report and literature review

    Science.gov (United States)

    Zou, Hai; Pan, Ke-Hua; Wu, Liang; Pan, Hong-Ying; Ding, Ya-Hui; Zheng, Ming-Hua

    2016-01-01

    NK/T cell lymphoma (NKTCL) is a common disease which is a threat to human health. Nasal NKTCL is a rare but serious type of systemic lymphoma because of its high mortality rate and serious complications. In this case report, we describe a male who presented with nasal blockage in the right side, a fever of one month duration and a soy-like, painless and gradually increasing mass in the right submandibular region due to nasal NKTCL. The patient had no significant medical history and the initial clinical symptoms were nasal blockage. Contrast computed tomography showed that the nasopharyngeal mucosa was thickened and that the celiac and retroperitoneal lymphaden was intumescent. Finally a biopsy, guided by nasal endoscopy and examined using flow cytometry confirmed a diagnosis of NKTCL. Nasal NKTCL is rare and has no unique characteristics at first presentation, such as epidemiology and obvious clinical manifestation. As no effective therapy is currently available for this disease, early diagnosis and therapy of nasal NKTCL remains challenging. PMID:26885897

  20. 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.

  1. 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

  2. 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...

  3. 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

  4. The tumor antigen N-glycolyl-GM3 is a human CD1d ligand capable of mediating B cell and natural killer T cell interaction.

    Science.gov (United States)

    Gentilini, M Virginia; Pérez, M Eugenia; Fernández, Pablo Mariano; Fainboim, Leonardo; Arana, Eloísa

    2016-05-01

    The expression of N-glycolyl-monosialodihexosyl-ganglioside (NGcGM3) in humans is restricted to cancer cells; therefore, it is a tumor antigen. There are measurable quantities of circulating anti-NGcGM3 antibodies (aNGcGM3 Abs) in human serum. Interestingly, some people have circulating Ag-specific immunoglobulins G (IgGs) that are capable of complement mediated cytotoxicity against NGcGM3 positive cells, which is relevant for tumor surveillance. In light of the chemical nature of Ag, we postulated it as a candidate ligand for CD1d. Furthermore, we hypothesize that the immune mechanism involved in the generation of these Abs entails cross talk between B lymphocytes (Bc) and invariant natural killer T cells (iNKT). Combining cellular techniques, such as flow cytometry and biochemical assays, we demonstrated that CD1d binds to NGcGM3 and that human Bc present NGcGM3 in a CD1d context according to two alternative strategies. We also showed that paraformaldehyde treatment of cells expressing CD1d affects the presentation. Finally, by co-culturing primary human Bc with iNKT and measuring Ki-67 expression, we detected a reproducible increment in the proliferation of the iNKT population when Ag was on the medium. Our findings identify a novel, endogenous, human CD1d ligand, which is sufficiently competent to stimulate iNKT. We postulate that CD1d-restricted Bc presentation of NGcGM3 drives effective iNKT activation, an immunological mechanism that has not been previously described for humans, which may contribute to understanding aNGcGM3 occurrence. PMID:26969612

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  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. 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

  12. 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

  13. Pleural fluid soluble triggering receptor expressed on myeloid cells-1 as a marker of bacterial infection: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Jiang Hong-Ni

    2011-10-01

    Full Text Available Abstract Background Pleural infection is a common clinical problem. Its successful treatment depends on rapid diagnosis and early initiation of antibiotics. The measurement of soluble triggering receptor expressed in myeloid cells-1 (sTREM-1 level in pleural effusions has proven to be a valuable diagnostic tool for differentiating bacterial effusions from effusions of other etiologies. Herein, we performed a meta-analysis to assess the accuracy of pleural fluid sTREM-1 in the diagnosis of bacterial infection. Methods We searched Web of Knowledge and Medline from 1990 through March 2011 for studies reporting diagnostic accuracy data regarding the use of sTREM-1 in the diagnosis of bacterial pleural effusions. Pooled sensitivity and specificity and summary measures of accuracy and Q* were calculated. Results Overall, the sensitivity of sTREM-1was 78% (95% CI: 72%-83%; the specificity was 84% (95% CI: 80%-87%; the positive likelihood ratio was 6.0 (95% CI: 3.3-10.7; and the negative likelihood ratio was 0.22 (95% CI: 0.12-0.40. The area under the SROC curve for sTREM-1 was 0.92. Statistical heterogeneity and inconsistency were found for sensitivity (p = 0.015, χ2 = 15.73, I2 = 61.9%, specificity (p = 0.000, χ2 = 29.90, I2 = 79.9%, positive likelihood ratio (p = 0.000, χ2 = 33.09, I2 = 81.9%, negative likelihood ratio (p = 0.008, χ2 = 17.25, I2 = 65.2%, and diagnostic odds ratio (p = 0.000, χ2 = 28.49, I2 = 78.9%. A meta-regression analysis performed showed that the Quality Assessment of Diagnostic Accuracy Studies score (p = 0.3245; RDOR, 4.34; 95% CI, 0.11 to 164.01, the Standards for Reporting of Diagnostic Accuracy score (p = 0.3331; RDOR, 1.70; 95% CI, 0.44 to 6.52, lack of blinding (p = 0.7439; RDOR, 0.60; 95% CI, 0.01 to 33.80, and whether the studies were prospective or retrospective studies (p = 0.2068; RDOR, 7.44; 95% CI, 0.18 to 301.17 did not affect the test accuracy. A funnel plot for publication bias suggested a remarkable trend

  14. 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...

  15. 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.

  16. 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

  17. 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

  18. MTP regulated by an alternate promoter is essential for NKT cell development

    OpenAIRE

    Dougan, Stephanie K.; Rava, Paul; Hussain, M. Mahmood; Blumberg, Richard S.

    2007-01-01

    Microsomal triglyceride transfer protein (MTP), an endoplasmic reticulum lipid transfer protein critical for apolipoprotein B (apoB) secretion, regulates CD1d antigen presentation. We identified MTP variant 1 (MTPv1), a novel splice variant of mouse MTP, by polymerase chain reaction and Northern analysis in non–apoB-secreting tissues, including thymocytes and antigen-presenting cells (APCs). Edman degradation of MTPv1 isolated from transfected cells revealed three unique residues; however, re...

  19. 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...

  20. Diskriminerad, trakasserad, kränkt? : En kvantitativ studie om hur elever upplever skolans likabehandlingsarbete

    OpenAIRE

    Zaitseva, Margarita; Peterzon, Sofia

    2014-01-01

    Studien handlar om i vilken omfattning eleverna känner sig delaktiga i skolanslikabehandlingsarbete samt i vilken omfattning eleverna upplever förekomsten avdiskriminering, trakasserier och kränkande behandling i skolan. Syftet är attkartlägga elevernas uppfattning om skolans likabehandlingsarbete samt förekomstenav kränkande behandling i skolans olika miljöer. Vi har valt ett kvantitativtangreppssätt då vi genomfört en enkätstudie som lämnats ut till totalt 101 elever iårskurs fem. Resultate...

  1. 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...

  2. Fysikattityder : Sambandet mellan fysikattityder och tilltänkt eftergymnasial fysikutbildning

    OpenAIRE

    Larsson, Lars-Erik

    2013-01-01

    Hur studenter klarar sina introduktionskurser i fysik på universitetet beror till stor del på deras attityder till fysik och fysikundervisning. Studenternas attityd påverkar hur dem arbetar med föreläsningar, lektioner, laborationer och kurslitteratur, och avgör hur studenterna gör för att tolka, resonera och bygga förståelse kring kursinnehållet. Det finns utförliga studier gjorda om vilka attityder som är fördelaktiga för fysikstudier på universitetsnivå. Men det finns väldigt lite forsknin...

  3. 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.

  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. 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...

  6. 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....

  7. 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.

  8. Clonal deleted latent membrane protein 1 variants of Epstein-Barr virus are predominant in European extranodal NK/T lymphomas and disappear during successful treatment.

    Science.gov (United States)

    Halabi, Mohamad Adnan; Jaccard, Arnaud; Moulinas, Rémi; Bahri, Racha; Al Mouhammad, Hazar; Mammari, Nour; Feuillard, Jean; Ranger-Rogez, Sylvie

    2016-08-15

    Extranodal natural killer/T-cell lymphomas (NK/TL), rare in Europe, are Epstein-Barr virus (EBV) associated lymphomas with poor outcomes. Here, we determined the virus type and analyzed the EBV latent membrane protein-1 (LMP1) gene sequence in NK/TL from French patients. Six clones of viral LMP1 were sequenced by Sanger technology in blood from 13 patients before treatment with an l-asparaginase based regimen and, for 8 of them, throughout the treatment. Blood LMP1 sequences from 21 patients without any known malignancy were tested as controls. EBV Type A was identified for 11/13 patients and for all controls. Before treatment, a clonal LMP1 gene containing a 30 bp deletion (del30) was found in 46.1% of NK/TL and only in 4.8% of controls. Treatment was less effective in these patients who died more rapidly than the others. Patients with a deleted strain evolving toward a wild-type strain during treatment reached complete remission. The LMP1 gene was sequenced by highly sensitive next-generation sequencing technology in five NK/TL nasopharyngeal biopsies, two of them originating from the previous patients. Del30 was present in 100% of the biopsies; two viruses at least coexisted in three biopsies. These results suggest that del30 may be associated with poor prognosis NK/TL and that strain evolution could be used as a potential marker to monitor treatment. PMID:27061907

  9. 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...

  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. Reconstitution models to evaluate natural killer T cell function in tumor control.

    Science.gov (United States)

    Gebremeskel, Simon; Slauenwhite, Drew; Johnston, Brent

    2016-01-01

    Natural killer T (NKT) cells are glycolipid-reactive T lymphocytes that function in immunosurveillance and immune regulation. However, reduced tumor control in NKT cell-deficient Jα18(-/-) mice may be confounded by an overall reduction in T-cell receptor (TCR) repertoire diversity in these animals. Mechanistic studies are also hindered by a lack of tools to target molecules specifically in NKT cells. To address these issues, we developed protocols to expand functional NKT cells and stably reconstitute them in Jα18(-/-) mice. In vivo delivery of α-galactosylceramide (α-GalCer)-loaded dendritic cells expanded NKT cells in wild-type mice without skewing CD4 or TCR Vβ expression profiles. Expanded NKT cells exhibited enhanced cytokine responses upon re-stimulation with glycolipid or CD3 ligation. Adoptive transfer of recently expanded wild-type or interferon (IFN)-γ(-/-) NKT cells protected recipient Jα18(-/-) mice from B16 melanoma metastasis without the need for additional glycolipid stimulation. However, NKT cell reconstitution in recipient Jα18(-/-) mice was short lived. Long-term reconstitution was only achieved when expanded NKT cells were transferred into sublethally irradiated recipients. Thirty days after transfer, NKT cell numbers, phenotype and α-GalCer-induced cytokine responses were equivalent to naive wild-type mice. Jα18(-/-) recipients reconstituted with wild-type or IFN-γ(-/-) NKT cells were both protected from B16 melanoma metastasis following α-GalCer treatment, and NK cell transactivation was intact in mice reconstituted with IFN-γ(-/-) NKT cells. These studies validate the use of reconstitution protocols to investigate the mechanisms of NKT cell immune function, demonstrating that NKT cell-derived IFN-γ and the altered TCR repertoire in Jα18(-/-) mice do not impact NKT cell-mediated antitumor responses. PMID:26095148

  12. P02.03INCREASED COUNTS OF NK AND NKT CELLS ARE ASSOCIATED WITH PROLONGED SURVIVAL IN PRIMARY GLIOBLASTOMA PATIENTS TREATED WITH DENDRITIC CELL IMMUNOTHERAPY IN COMBINATION WITH RADIO- AND CHEMO-THERAPY

    OpenAIRE

    Pellegatta, S.; Eoli, M.; Cantini, G.; Anghileri, E.; Antozzi, C.; S. Frigerio; Bruzzone, M.; Pollo, B; Parati, E; Finocchiaro, G.

    2014-01-01

    Two clinical studies, DENDR1 and DENDR2 including, respectively, the treatment of first diagnosis and recurrent glioblastoma (GB) patients with dendritic cells (DCs) loaded with autologous tumor lysate are currently active at Istituto Neurologico Besta, Milan. Our first results obtained on a group of recurrent GB patients demonstrated that the response of NK cells correlates with significantly prolonged survival. Here we provide results of the interim analysis on 22 patients affected by prima...

  13. 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...

  14. 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...

  15. Mono-(2-Ethylhexyl) Phthalate (MEHP) Promotes Invasion and Migration of Human Testicular Embryonal Carcinoma Cells1

    OpenAIRE

    Yao, Pei-Li; Lin, Yi-Chen; Richburg, John H.

    2012-01-01

    Testicular dysgenesis syndrome refers to a collection of diseases in men, including testicular cancer, that arise as a result of abnormal testicular development. Phthalates are a class of chemicals used widely in the production of plastic products and other consumer goods. Unfortunately, phthalate exposure has been linked to reproductive dysfunction and has been shown to adversely affect normal germ cell development. In this study, we show that mono-(2-ethylhexyl) phthalate (MEHP) induces mat...

  16. 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...

  17. 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

  18. 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

  19. Proinflammatory S100 Proteins Regulate the Accumulation of Myeloid-Derived Suppressor Cells1

    OpenAIRE

    Sinha, Pratima; Okoro, Chinonyerem; Foell, Dirk; Freeze, Hudson H.; Ostrand-Rosenberg, Suzanne; Srikrishna, Geetha

    2008-01-01

    Chronic inflammation is a complex process that promotes carcinogenesis and tumor progression; however, the mechanisms by which specific inflammatory mediators contribute to tumor growth remain unclear. We and others recently demonstrated that the inflammatory mediators IL-1β, IL-6, and PGE2 induce accumulation of myeloid-derived suppressor cells (MDSC) in tumor-bearing individuals. MDSC impair tumor immunity and thereby facilitate carcinogenesis and tumor progression by inhibiting T and NK ce...

  20. Mechanism of T-cell tolerance induced by myeloid-derived suppressor cells1

    OpenAIRE

    Nagaraj, Srinivas; Schrum, Adam G.; Cho, Hyun-Il; Celis, Esteban; Gabrilovich, Dmitry I.

    2010-01-01

    Antigen-specific T-cell tolerance plays a critical role in tumor escape. Recent studies implicated myeloid-derived suppressor cells (MDSC) in the induction of CD8+ T-cell tolerance in tumor-bearing hosts. However, the mechanism of this phenomenon remained unclear. We have found that incubation of antigen-specific CD8+ T cells, with peptide-loaded MDSC, did not induce signaling downstream of TCR. However, it prevented subsequent signaling from peptide-loaded dendritic cells. Using double TCR t...

  1. 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...

  2. 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.

  3. 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

  4. Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells1

    OpenAIRE

    Glunde, Kristine; Sandra E. Guggino; Solaiyappan, Meiyappan; Pathak, Arvind P.; Ichikawa, Yoshitaka; Bhujwalla, Zaver M.

    2003-01-01

    Cancer cells invade by secreting degradative enzymes, which are sequestered in lysosomal vesicles. In this study, the impact of an acidic extracellular environment on lysosome size, number, and distance from the nucleus in human mammary epithelial cells (HMECs) and breast cancer cells of different degrees of malignancy was characterized because the physiological microenvironment of tumors is frequently characterized by extracellular acidity. An acidic extracellular pH (pHe) resulted in a dist...

  5. 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.)

  6. 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...

  7. GATA-3 regulates the homeostasis and activation of CD8+ T cells1

    OpenAIRE

    Tai, Tzong-Shyuan; Pai, Sung-Yun; Ho, I-Cheng

    2012-01-01

    GATA-3, a C2C2 type zinc finger transcription factor, regulates many steps of T cell development and differentiation. It is also required for optimal production of type 2 cytokines by CD8+ T cells. However, its role in the development and function of this subset of T cells is still poorly characterized. Here we report that GATA-3 is required for MHC-mediated positive selection and final maturation of CD8 single positive thymocytes. Deficiency of GATA-3 mediated by a CD4cre transgene led to ag...

  8. 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....

  9. 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.

  10. Mutation of the Traj18 gene segment using TALENs to generate Natural Killer T cell deficient mice.

    Science.gov (United States)

    Zhang, Jingjing; Bedel, Romain; Krovi, S Harsha; Tuttle, Kathryn D; Zhang, Bicheng; Gross, James; Gapin, Laurent; Matsuda, Jennifer L

    2016-01-01

    Invariant Natural Killer T (iNKT) cells are a unique subset of T lymphocytes that have been implicated in both promoting and suppressing a multitude of immune responses. In mice, iNKT cells express T cell antigen receptors (TCRs) comprising a unique TCRα rearrangement between the Trav11 and Traj18 gene segments. When paired with certain Trbv TCRβ chains, these TCRs recognize lipid antigens presented by the major histocompatibility complex (MHC) class I-like molecule, CD1d. Until recently, the sole model of iNKT deficiency targeted the Jα18, which is absolutely required to form the TCR with the appropriate antigenic specificity. However, these mice were demonstrated to have a large reduction in TCR repertoire diversity, which could confound results arising from studies using these mice. Here, we have created a new NKT-deficient mouse strain using transcription activator-like effector nuclease (TALEN) technology to only disrupt the expression of Jα18, leaving the remaining Jα repertoire unperturbed. We confirm that these mice lack iNKT cells and do not respond to lipid antigen stimulation while the development of conventional T cells, regulatory T cells, and type Ib NKT cells is normal. This new mouse strain will serve as a new model of iNKT cell deficiency to facilitate our understanding of iNKT biology. PMID:27256918

  11. Local Production of Interferon Gamma by Invariant Natural Killer T cells Modulates Acute Lyme Carditis

    Science.gov (United States)

    Olson, Chris M.; Bates, Tonya C.; Izadi, Hooman; Radolf, Justin D.; Huber, Sally A.; Boyson, Jonathan E.; Anguita, Juan

    2009-01-01

    The Lyme disease spirochete, Borrelia burgdorferi, is the only known human pathogen that directly activates invariant natural killer T (iNKT) cells. The number and activation kinetics of iNKT cells vary greatly among different strains of mice. We now report the role of the iNKT cell response in the pathogenesis of Lyme disease using C57Bl/6 mice, a strain with optimal iNKT cell activation that is resistant to the development of spirochetal-induced inflammation. During experimental infection of B6 mice with B. burgdorferi, iNKT cells localize to the inflamed heart where they are activated by CD1d-expressing macrophages. Activation of iNKT cells in vivo results in the production of IFNγ, which we demonstrate ameliorates the severity of murine Lyme carditis by at least two mechanisms. First, IFNγ enhances the recognition of B. burgdorferi by macrophages, leading to increased phagocytosis of the spirochete. Secondly, IFNγ activation of macrophages increases the surface expression of CD1d, thereby facilitating further iNKT activation. Collectively, our data demonstrate that in the resistant background, B6, iNKT cells modulate the severity of murine Lyme carditis through the action of IFNγ, which appears to self-renew through a positive feedback loop during infection. PMID:19265151

  12. Mutation of the Traj18 gene segment using TALENs to generate Natural Killer T cell deficient mice

    Science.gov (United States)

    Zhang, Jingjing; Bedel, Romain; Krovi, S. Harsha; Tuttle, Kathryn D.; Zhang, Bicheng; Gross, James; Gapin, Laurent; Matsuda, Jennifer L.

    2016-01-01

    Invariant Natural Killer T (iNKT) cells are a unique subset of T lymphocytes that have been implicated in both promoting and suppressing a multitude of immune responses. In mice, iNKT cells express T cell antigen receptors (TCRs) comprising a unique TCRα rearrangement between the Trav11 and Traj18 gene segments. When paired with certain Trbv TCRβ chains, these TCRs recognize lipid antigens presented by the major histocompatibility complex (MHC) class I-like molecule, CD1d. Until recently, the sole model of iNKT deficiency targeted the Jα18, which is absolutely required to form the TCR with the appropriate antigenic specificity. However, these mice were demonstrated to have a large reduction in TCR repertoire diversity, which could confound results arising from studies using these mice. Here, we have created a new NKT-deficient mouse strain using transcription activator-like effector nuclease (TALEN) technology to only disrupt the expression of Jα18, leaving the remaining Jα repertoire unperturbed. We confirm that these mice lack iNKT cells and do not respond to lipid antigen stimulation while the development of conventional T cells, regulatory T cells, and type Ib NKT cells is normal. This new mouse strain will serve as a new model of iNKT cell deficiency to facilitate our understanding of iNKT biology. PMID:27256918

  13. C-Reactive Protein-Bound Enzymatically Modified Low-Density Lipoprotein Does Not Transform Macrophages into Foam Cells1

    OpenAIRE

    Singh, Sanjay K.; Suresh, Madathilparambil V.; Prayther, Deborah C; Moorman, Jonathan P.; Rusiñol, Antonio E.; Agrawal, Alok

    2008-01-01

    The formation of low-density lipoprotein (LDL) cholesterol-loaded macrophage foam cells contributes to the development of atherosclerosis. C-reactive protein (CRP) binds to atherogenic forms of LDL, but the role of CRP in foam cell formation is unclear. In this study, we first explored the binding site on CRP for enzymatically modified LDL (E-LDL), a model of atherogenic LDL to which CRP binds. As reported previously, phosphocholine (PCh) inhibited CRP-E-LDL interaction, indicating the involv...

  14. 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.

  15. 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.

  16. CD8+ CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells1

    OpenAIRE

    Yamazaki, Sayuri; Dudziak, Diana; Heidkamp, Gordon F; Fiorese, Christopher; Bonito, Anthony J.; Inaba, Kayo; Nussenzweig, Michel C.; Steinman, Ralph M.

    2008-01-01

    Foxp3+CD25+CD4+ regulatory T cells (T reg) mediate immunological self-tolerance and suppress immune responses. A subset of dendritic cells (DCs) in the intestine is specialized to induce T reg in a transforming growth factor (TGF)-β and retinoic acid (RA) dependent manner to allow for oral tolerance. Here we compare two major DC subsets from mouse spleen. We find that CD8+ DEC-205/CD205+ DCs, but not the major fraction of CD8− dendritic cell inhibitory receptor-2 (DCIR2)+ DCs, induce function...

  17. Mechanism regulating reactive oxygen species in tumor induced myeloid-derived suppressor cells1: MDSC and ROS in cancer

    OpenAIRE

    Corzo, Cesar A.; Cotter, Matthew J.; Cheng, Pingyan; Cheng, Fendong; Kusmartsev, Sergei; Sotomayor, Eduardo; Padhya, Tapan; McCaffrey, Thomas V.; McCaffrey, Judith C.; Gabrilovich, Dmitry I.

    2009-01-01

    Myeloid-derived suppressor cells (MDSC) are a major component of the immune suppressive network described in cancer and many other pathological conditions. Recent studies have demonstrated that one of the major mechanisms of MDSC-induced immune suppression is mediated by reactive oxygen species (ROS). However, the mechanism of this phenomenon remained unknown. In this study we observed a substantial up-regulation of ROS by MDSC in all of seven different tumor models and in patients with head ...

  18. The Novel Retinoid, 9cUAB30, Inhibits Telomerase and Induces Apoptosis in HL60 Cells1

    OpenAIRE

    LOVE, WILLIAM K.; DeAngelis, J. Tyson; Berletch, Joel B.; Phipps, Sharla MO; Andrews, Lucy G.; Brouillette, Wayne J.; Muccio, Donald D.; Tollefsbol, Trygve O.

    2008-01-01

    Telomerase, a ribonucleoprotein important to neoplastic immortality, is up-regulated in approximately 85% of cancers, including leukemias. In this study, 9cUAB30, a novel retinoic acid, resulted in differentiation of HL60 leukemia cells as indicated by morphologic changes characteristic of granulocytes. It also caused a down-regulation of hTERT gene expression and a decrease in telomerase activity. Telomerase inhibition was followed by loss of proliferative capacity, induction of apoptosis, a...

  19. 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...

  20. High-throughput Immunoblotting Identifies Biotin-dependent Signaling Proteins in HepG2 Hepatocarcinoma Cells1

    OpenAIRE

    Rodriguez-Melendez, Rocio; Griffin, Jacob B.; Sarath, Gautam; Zempleni, Janos

    2005-01-01

    Biotin affects the abundance of mRNA coding for approximately 10% of genes expressed in human-derived hepatocarcinoma (HepG2) cells. Here, we determined whether effects of biotin on gene expression are associated with changes in the abundance of distinct proteins in cell signaling and structure. HepG2 cells were cultured in media containing the following concentrations of biotin: 0.025 nmol/L (denoted “deficient”), 0.25 nmol/L (“physiological” = control), and 10 nmol/L (“pharmacological”) for...

  1. TOLERIZATION OF A TYPE I ALLERGIC IMMUNE RESPONSE THROUGH TRANSPLANTATION OF GENETICALLY MODIFIED HEMATOPOIETIC STEM CELLS1

    OpenAIRE

    Baranyi, Ulrike; Linhart, Birgit; Pilat, Nina; Bagley, Jessamyn; Muehlbacher, Ferdinand; Iacomini, John; Valenta, Rudolf; Wekerle, Thomas

    2008-01-01

    Allergy represents a hypersensitivity disease which affects more than 25% of the population in industrialized countries. The underlying type I allergic immune reaction occurs in predisposed atopic individuals in response to otherwise harmless antigens (i.e. allergens) and is characterized by the production of allergen-specific IgE, an allergen-specific T cell response and the release of biologically active mediators such as histamine from mast cells and basophils. Regimens permanently toleriz...

  2. 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...

  3. 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

  4. 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...

  5. INDOLEAMINE 2,3-DIOXYGENASE INDUCES EXPRESSION OF A NOVEL TRYPTOPHAN TRANSPORTER IN MOUSE AND HUMAN TUMOR CELLS1

    OpenAIRE

    Silk, Jonathan D.; Lakhal, Samira; Laynes, Robert; Vallius, Laura; Karydis, Ioannis; Marcea, Cornelius; Boyd, C. A. Richard; Cerundolo, Vincenzo

    2011-01-01

    Indoleamine 2,3 dioxygenase (IDO) is the rate-limiting enzyme in the kynurenine pathway, catabolizing tryptophan to kynurenine. Tryptophan depletion by IDO expressing tumors is a common mechanism of immune evasion inducing regulatory T cells and inhibiting effector T cells. As mammalian cells cannot synthesize tryptophan, it remains unclear how IDO positive tumor cells overcome the detrimental effects of local tryptophan depletion.

  6. 20 MV/m accelerating gradient with heat treatment of a six cell, 1.5 GHz cavity for TESLA

    International Nuclear Information System (INIS)

    In order to use superconducting RF accelerating structures in the construction of a high energy linear collider, the structures must be designed to meet specific goals. These include low peak surface electric fields, good higher order mode power extraction from the ends, maximum accelerating gradient and, above all, low cost per unit accelerating voltage. Such a structure has been designed, manufactured and tested. Preliminary results have been reported. The cavity was then mechanically braced with Niobium braces and then heat treated. The final test gave 20 MV/m accelerating field. Details of some difficulties encountered will also be presented at this time

  7. Advances in basic and clinical immunology in 2006.

    Science.gov (United States)

    Chinen, Javier; Shearer, William T

    2007-08-01

    This article reviews the progress in the field of basic and clinical immunology in 2006, focusing on the articles published in the Journal. The role of Toll-like receptors in the immune response was explored in detail in several articles. The knowledge gained in these investigations is being used to develop strategies that enhance the immunogenicity of vaccines to prevent infectious diseases and to have an immunomodulatory effect on allergic diseases. Other components of the innate immunity reported on were the recognition of allergens with lipid-derived motifs by CD1d-restricted T cells and the role of dendritic cells in the development of an allergic response. More than 120 primary immunodeficiencies were defined at a molecular level, and biological agents such as TNF-alpha antagonists and IFN-alpha were shown to have therapeutic use. New anti-HIV drugs that block cell entry were proven to be effective, thus offering alternative therapies to respond to the development of multidrug-resistant HIV strains. The modern understanding of immunologic concepts is helping to elucidate the mechanisms of defense against viruses, bacteria, and parasites; as a result, strategies to improve management and prevention continue to emerge. PMID:17590425

  8. Redox proteomic profiling of neuroketal-adducted proteins in human brain: Regional vulnerability at middle age increases in the elderly.

    Science.gov (United States)

    Domínguez, Mayelín; de Oliveira, Eliandre; Odena, María Antonia; Portero, Manuel; Pamplona, Reinald; Ferrer, Isidro

    2016-06-01

    Protein lipoxidation was assessed in the parietal cortex (PC), frontal cortex (FC), and cingulate gyrus (CG) in middle-aged and old-aged individuals with no clinical manifestations of cognitive impairment, in order to increase understanding of regional brain vulnerability to oxidative damage during aging. Twenty-five lipoxidized proteins were identified in all the three regions although with regional specificities, by using redox proteomics to detect target proteins of neuroketals (NKT) adduction. The number of cases with NKT-adducted proteins was higher in old-aged individuals but most oxidized proteins were already present in middle-aged individuals. Differences in vulnerability to oxidation were dependent on the sub-cellular localization, secondary structure, and external exposition of certain amino acids. Lipoxidized proteins included those involved in energy metabolism, cytoskeleton, proteostasis, neurotransmission and O2/CO2, and heme metabolism. Total NKT and soluble oligomer levels were estimated employing slot-blot, and these were compared between age groups. Oligomers increased with age in PC and FC; NKT significantly increased with age in FC, whereas total NKT and oligomer levels were not modified in CG, thus highlighting differences in brain regional vulnerability with age. Oligomers significantly correlated with NKT levels in the three cortical regions, suggesting that protein NKT adduction parallels soluble oligomer formation. PMID:26968793

  9. Testosterone increases susceptibility to amebic liver abscess in mice and mediates inhibition of IFNγ secretion in natural killer T cells.

    Science.gov (United States)

    Lotter, Hannelore; Helk, Elena; Bernin, Hannah; Jacobs, Thomas; Prehn, Cornelia; Adamski, Jerzy; González-Roldán, Nestor; Holst, Otto; Tannich, Egbert

    2013-01-01

    Amebic liver abscess (ALA), a parasitic disease due to infection with the protozoan Entamoeba histolytica, occurs age and gender dependent with strong preferences for adult males. Using a mouse model for ALA with a similar male bias for the disease, we have investigated the role of female and male sexual hormones and provide evidence for a strong contribution of testosterone. Removal of testosterone by orchiectomy significantly reduced sizes of abscesses in male mice, while substitution of testosterone increased development of ALA in female mice. Activation of natural killer T (NKT) cells, which are known to be important for the control of ALA, is influenced by testosterone. Specifically activated NKT cells isolated from female mice produce more IFNγ compared to NKT cells derived from male mice. This high level production of IFNγ in female derived NKT cells was inhibited by testosterone substitution, while the IFNγ production in male derived NKT cells was increased by orchiectomy. Gender dependent differences were not a result of differences in the total number of NKT cells, but a result of a higher activation potential for the CD4(-) NKT cell subpopulation in female mice. Taken together, we conclude that the hormone status of the host, in particular the testosterone level, determines susceptibility to ALA at least in a mouse model of the disease. PMID:23424637

  10. 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

  11. 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...

  12. 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...

  13. Natural Killer T Cells in Adipose Tissue Are Activated in Lean Mice

    OpenAIRE

    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 ...

  14. 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

  15. 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...

  16. 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...

  17. 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...

  18. Invariant Natural Killer T-Cell Control of Type 1 Diabetes: A Dendritic Cell Genetic Decision of a Silver Bullet or Russian Roulette

    OpenAIRE

    Driver, John P.; Scheuplein, Felix; Chen, Yi-Guang; Grier, Alexandra E.; Wilson, S. Brian; Serreze, David V.

    2009-01-01

    OBJECTIVE In part, activation of invariant natural killer T (iNKT)-cells with the superagonist α-galactosylceramide (α-GalCer) inhibits the development of T-cell–mediated autoimmune type 1 diabetes in NOD mice by inducing the downstream differentiation of antigen-presenting dendritic cells (DCs) to an immunotolerogenic state. However, in other systems iNKT-cell activation has an adjuvant-like effect that enhances rather than suppresses various immunological responses. Thus, we tested whether ...

  19. 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.

  20. 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.)

  1. 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

  2. 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.

  3. The impact of pre-existing memory on differentiation of newly recruited naïve CD8 T cells1

    OpenAIRE

    Martin, Matthew D.; Wirth, Thomas C; Lauer, Peter; Harty, John T.; Vladimir P. Badovinac

    2011-01-01

    One goal of immunization is to generate memory CD8 T cells of sufficient quality and quantity to confer protection against infection. It has been shown that memory CD8 T cell differentiation in vivo is controlled, at least in part, by the amount and duration of infection, antigen and inflammatory cytokines present early after the initiation of the response. Here, using models of anti-vectorial immunity we investigated the impact of pre-existing immunity on development and differentiation of v...

  4. Transition from Preinvasive Carcinoma In Situ to Seminoma Is Accompanied by a Reduction of Connexin 43 Expression in Sertoli Cells and Germ Cells1

    OpenAIRE

    Brehm, Ralph; Rüttinger, Christina; Fischer, Petra; Gashaw, Isabella; Winterhager, Elke; Kliesch, Sabine; Bohle, Rainer M.; Steger, Klaus; Bergmann, Martin ,

    2006-01-01

    Carcinoma in situ (CIS) represents the preinvasive stage of human germ cell tumors, but the mechanism leading to pubertal proliferation and invasive malignancy remains unknown. Among testicular gap junctional proteins, connexin 43 (Cx43) represents the predominant Cx, and, previously, an inverse correlation between synthesis of Cx43 protein and progression of tumor development was detected. In the present study, using cDNA microarray analysis, in situ hybridization, semiquantitative reverse t...

  5. Myeloid-Derived Suppressor Cells Down-Regulate L-Selectin Expression on CD4+ and CD8+ T Cells1

    OpenAIRE

    Hanson, Erica M.; Clements, Virginia K.; Sinha, Pratima; Ilkovitch, Dan; Ostrand-Rosenberg, Suzanne

    2009-01-01

    Effective cell-mediated antitumor immunity requires the activation of tumor-reactive T cells and the trafficking of activated T cells to tumor sites. These processes involve the extravasation of lymphocytes from the blood and lymphatics, and their homing to lymph nodes and tumors. L-selectin (CD62L) is an important molecule in these processes. It directs naive lymphocytes to peripheral lymph nodes where they become activated and it traffics naive lymphocytes to inflammatory environments, such...

  6. 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...

  7. Sodium-Dependent Multivitamin Transporter Gene Is Regulated at the Chromatin Level by Histone Biotinylation in Human Jurkat Lymphoblastoma Cells1–3

    OpenAIRE

    Zempleni, Janos; Gralla, Michael; Camporeale, Gabriela; Hassan, Yousef I.

    2009-01-01

    The sodium-dependent multivitamin transporter (SMVT) is essential for mediating and regulating biotin entry into mammalian cells. In cells, holocarboxylase synthetase (HCS) mediates covalent binding of biotin to histones; biotinylation of lysine-12 in histone H4 (K12BioH4) causes gene repression. Here we propose a novel role for HCS in sensing and regulating levels of biotin in eukaryotic cells. We hypothesize that nuclear translocation of HCS increases in response to biotin supplementation; ...

  8. Dendritic Cells Expressing Triggering Receptor Expressed on Myeloid Cells-1 Correlate with Plaque Stability in Symptomatic and Asymptomatic Patients with Carotid Stenosis

    Science.gov (United States)

    Shao, Zhifei; Agrawal, Devendra K.

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory cells, including T-lymphocytes, dendritic cells (DCs) and macrophages that are responsible for progression and destabilization of atherosclerotic plaques. Stressed cells undergoing necrosis release molecules that act as endogenous danger signals to alert and activate innate immune cells. In atherosclerotic tissue the number of DCs increases with the progression of the lesion and produce several inflammatory cytokines and growth factors. Triggering receptor expressed on myeloid cells (TREM)-1 plays a crucial role in inflammation. However, relationship of DCs and the role of TREM-1 with the stability of atherosclerotic plaques have not been examined. In this study, we investigated the heterogeneity of the plaque DCs, myeloid (mDC1 and mDC2) and plasmacytoid (pDCs), and examined the expression of TREM-1 and their co-localization with DCs in the plaques from symptomatic (S) and asymptomatic (AS) patients with carotid stenosis. We found increased expression of HLA-DR, fascin, and TREM-1 and decreased expression of TREM-2 and α-smooth muscle actin in S compared to AS atherosclerotic carotid plaques. Both TREM-1 and fascin were co-localized suggesting increased expression of TREM-1 in plaque DCs of S compared to AS patients. These data were supported by increased mRNA transcripts of TREM-1 and decreased mRNA transcripts of TREM-2 in carotid plaques of S compared to AS patients. There was higher density of both CD1c+ mDC1 and CD141+ mDC2 in the carotid plaques from AS compared to S patients, where as the density of CD303+ pDCs were higher in the carotid plaques of S compared to AS patients. These findings suggest a potential role of pDCs and TREM-1 in atherosclerotic plaque vulnerability. Thus, newer therapies could be developed to selectively block TREM-1 for stabilizing atherosclerotic plaques. PMID:27148736

  9. A dynamic dual role of IL-2 signaling in the two-step differentiation process of adaptive regulatory T cells1

    OpenAIRE

    Guo, Zhiyong; Khattar, Mithun; Schroder, Paul M.; Miyahara, Yoshihiro; Wang, Guohua; He, Xiaoshung; Chen, Wenhao; Stepkowski, Stanislaw M.

    2013-01-01

    The molecular mechanism of the extrathymic generation of adaptive CD4+Foxp3+ regulatory T (iTreg) cells remains incompletely defined. We show that exposure of splenic CD4+CD25+Foxp3− cells to IL-2, but not other γc cytokines, resulted in Stat5 phosphorylation and induced Foxp3 expression in ~10% of the cells. Thus, IL-2/Stat5 signaling may be critical for Foxp3 induction in peripheral CD4+CD25+Foxp3− iTreg cell precursors. Herein, to further define the role of IL-2 in the formation of iTreg c...

  10. 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

  11. 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

  12. T-Independent Activation-Induced Cytidine Deaminase Expression, Class-Switch Recombination, and Antibody Production by Immature/Transitional 1 B Cells1

    OpenAIRE

    Ueda, Yoshihiro; Liao, Dongmei; Yang, Kaiyong; Patel, Anjali; Kelsoe, Garnett

    2007-01-01

    Inflammation elicits a splenic lymphopoiesis of unknown physiologic significance but one that juxtaposes developing B cells and exogenous Ag. We show that immature and transitional 1 (immature/T1) B cells constitutively express activation-induced cytidine deaminase and B lymphocyte-induced maturation protein 1 in amounts that support accelerated plasmacytic differentiation and limited class-switch recombination. In vivo, activation of immature/T1 B cells by TLR ligands or bacterial vaccine ra...

  13. 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...

  14. Histamine Directly and Synergistically with Lipopolysaccharide Stimulates Cyclooxygenase-2 Expression and Prostaglandin I2 and E2 Production in Human Coronary Artery Endothelial Cells1

    OpenAIRE

    Tan, Xiaoyu; Essengue, Suzanne; Talreja, Jaya; Reese, Jeff; Stechschulte, Daniel J.; Dileepan, Kottarappat N.

    2007-01-01

    Although histamine plays an essential role in inflammation, its influence on cyclooxygenases (COX) and prostanoid homeostasis is not well understood. Here, we investigated the effects of histamine on the expression of COX-1 and COX-2 and determined their contribution to the production of prostaglandin-E2 (PGE2), prostacyclin (PGI2) and thromboxane A2 (TXA2) in human coronary artery endothelial cells (HCAEC). Incubation of HCAEC monolayers with histamine resulted in marked increases in the exp...

  15. An Optimal Frequency in Ca2+ Oscillations for Stomatal Closure Is an Emergent Property of Ion Transport in Guard Cells1[OPEN

    Science.gov (United States)

    Minguet-Parramona, Carla; Hills, Adrian; Vialet-Chabrand, Silvere; Griffiths, Howard; Lawson, Tracy; Lew, Virgilio L.; Blatt, Michael R.

    2016-01-01

    Oscillations in cytosolic-free Ca2+ concentration ([Ca2+]i) have been proposed to encode information that controls stomatal closure. [Ca2+]i oscillations with a period near 10 min were previously shown to be optimal for stomatal closure in Arabidopsis (Arabidopsis thaliana), but the studies offered no insight into their origins or mechanisms of encoding to validate a role in signaling. We have used a proven systems modeling platform to investigate these [Ca2+]i oscillations and analyze their origins in guard cell homeostasis and membrane transport. The model faithfully reproduced differences in stomatal closure as a function of oscillation frequency with an optimum period near 10 min under standard conditions. Analysis showed that this optimum was one of a range of frequencies that accelerated closure, each arising from a balance of transport and the prevailing ion gradients across the plasma membrane and tonoplast. These interactions emerge from the experimentally derived kinetics encoded in the model for each of the relevant transporters, without the need of any additional signaling component. The resulting frequencies are of sufficient duration to permit substantial changes in [Ca2+]i and, with the accompanying oscillations in voltage, drive the K+ and anion efflux for stomatal closure. Thus, the frequency optima arise from emergent interactions of transport across the membrane system of the guard cell. Rather than encoding information for ion flux, these oscillations are a by-product of the transport activities that determine stomatal aperture. PMID:26628748

  16. Geographical venom variations of the Southeast Asian monocled cobra (Naja kaouthia): venom-induced neuromuscular depression and antivenom neutralization.

    Science.gov (United States)

    Tan, Kae Yi; Tan, Choo Hock; Sim, Si Mui; Fung, Shin Yee; Tan, Nget Hong

    2016-01-01

    The Southeast Asian monocled cobras (Naja kaouthia) exhibit geographical variations in their venom proteomes, especially on the composition of neurotoxins. This study compared the neuromuscular depressant activity of the venoms of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V), and the neutralization of neurotoxicity by a monospecific antivenom. On chick biventer cervicis nerve-muscle preparation, all venoms abolished the indirect twitches, with NK-T venom being the most potent (shortest t90, time to 90% twitch inhibition), followed by NK-V and NK-M. Acetylcholine and carbachol failed to reverse the blockade, indicating irreversible/pseudo-irreversible post-synaptic neuromuscular blockade. KCl restored the twitches variably (NK-M preparation being the least responsive), consistent with different degree of muscle damage. The findings support that NK-T venom has the most abundant curarimimetic alpha-neurotoxins, while NK-M venom contains more tissue-damaging cytotoxins. Pre-incubation of tissue with N. kaouthia monovalent antivenom (NKMAV) prevented venom-induced twitch depression, with the NK-T preparation needing the largest antivenom dose. NKMAV added after the onset of neuromuscular depression could only halt the inhibitory progression but failed to restore full contraction. The findings highlight the urgency of early antivenom administration to sequester as much circulating neurotoxins as possible, thereby hastening toxin elimination from the circulation. In envenomed mice, NKMAV administered upon the first neurological sign neutralized the neurotoxic effect, with the slowest full recovery noticed in the NK-T group. This is consistent with the high abundance of neurotoxins in the NK-T venom, implying that a larger amount or repeated dosing of NKMAV may be required in NK-T envenomation. PMID:26972756

  17. 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

  18. 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.

  19. 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.

  20. IL32γ activates natural killer receptor-expressing innate immune cells to produce IFNγ via dendritic cell-derived IL12.

    Science.gov (United States)

    Lee, Sung Won; Park, Hyun Jung; Lee, Kwang Soo; Park, Se-Ho; Kim, Soohyun; Jeon, Sung Ho; Hong, Seokmann

    2015-05-22

    The inflammatory cytokine IL32γ acts on dendritic cells (DCs) to produce IL12 and IL6, which are involved in the differentiation of Th1 and Th17 cells. Natural killer (NK) and NKT cells play important roles in IL12-mediated adaptive immune responses, such as antitumor immunity. Herein we demonstrate the effect of IL32γ on the activation of NK and NKT cells. Upon IL32γ stimulation, splenic NK and NKT cells could be activated, and this activation was dependent on both IL12 and DCs, which was confirmed by using IL12p35 knockout and CD11c-diphtheria toxin receptor transgenic mouse models. Furthermore, IL32γ could induce the production of proinflammatory cytokines by NKDCs, a subset of DCs expressing NK cell markers, known to enhance NKT cell function. Unlike conventional DCs, NKDCs produced IFNγ and TNFα rather than IL12 upon stimulation with IL32γ. Taken together, IL32γ will be useful as an adjuvant to boost the cytotoxicities of NK and NKT cells that play critical roles in antitumor immunity. PMID:25858316

  1. 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.

  2. Natural killer T cells activated by a lipopeptidophosphoglycan from Entamoeba histolytica are critically important to control amebic liver abscess.

    Science.gov (United States)

    Lotter, Hannelore; González-Roldán, Nestor; Lindner, Buko; Winau, Florian; Isibasi, Armando; Moreno-Lafont, Martha; Ulmer, Artur J; Holst, Otto; Tannich, Egbert; Jacobs, Thomas

    2009-05-01

    The innate immune response is supposed to play an essential role in the control of amebic liver abscess (ALA), a severe form of invasive amoebiasis due to infection with the protozoan parasite Entamoeba histolytica. In a mouse model for the disease, we previously demonstrated that Jalpha18(-/-) mice, lacking invariant natural killer T (iNKT) cells, suffer from more severe abscess development. Here we show that the specific activation of iNKT cells using alpha-galactosylceramide (alpha-GalCer) induces a significant reduction in the sizes of ALA lesions, whereas CD1d(-/-) mice develop more severe abscesses. We identified a lipopeptidophosphoglycan from E. histolytica membranes (EhLPPG) as a possible natural NKT cell ligand and show that the purified phosphoinositol (PI) moiety of this molecule induces protective IFN-gamma but not IL-4 production in NKT cells. The main component of EhLPPG responsible for NKT cell activation is a diacylated PI, (1-O-[(28:0)-lyso-glycero-3-phosphatidyl-]2-O-(C16:0)-Ins). IFN-gamma production by NKT cells requires the presence of CD1d and simultaneously TLR receptor signalling through MyD88 and secretion of IL-12. Similar to alpha-GalCer application, EhLPPG treatment significantly reduces the severity of ALA in ameba-infected mice. Our results suggest that EhLPPG is an amebic molecule that is important for the limitation of ALA development and may explain why the majority of E. histolytica-infected individuals do not develop amebic liver abscess. PMID:19436711

  3. 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...

  4. A designated centre for people with disabilities operated by RehabCare, Donegal

    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.

  5. 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.

  6. 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.

  7. Invariant natural killer T cell–natural killer cell interactions dictate transplantation outcome after α-galactosylceramide administration

    OpenAIRE

    Kuns, Rachel D.; Morris, Edward S.; MacDonald, Kelli P.A.; Markey, Kate A.; Helen M. Morris; Raffelt, Neil C.; Banovic, Tatjana; Don, Alistair L. J.; Rowe, Vanessa; Burman, Angela C.; Clouston, Andrew D; Farah, Camile; Besra, Gurdyal S.; Illarionov, Petr A.; Smyth, Mark J

    2009-01-01

    Invariant natural killer T cells (iNKT cells) have pivotal roles in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects. iNKT cells are activated through their T-cell receptors by glycolipid moieties (typically the α-galactosylceramide [α-GalCer] derivative KRN7000) presented within CD1d. We investigated the ability of modified α-GalCer molecules to differentially modulate alloreactivity and GVL. KRN7000 and the N-acyl variant, C20:2, were administered in multiple well-es...

  8. 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...

  9. 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.

  10. 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...

  11. 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...

  12. 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

  13. 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...

  14. Krisen i den Britiske Union

    DEFF Research Database (Denmark)

    2010-01-01

    betale for skotsk, walisisk og nordirsk selvbestemmelse. De tre store britiske partier er først lige begyndt at forholde sig til den krise der er for den Britiske Union og hvad de har tænkt sig at gøre for at løse problemerne vil vi vende tilbage til her i Orientering i den kommende tid....

  15. 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...

  16. 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...

  17. 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.

  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. 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.

  20. Peripheral blood mononuclear cells of patients with breast cancer can be reprogrammed to enhance anti-HER-2/neu reactivity and overcome myeloid-derived suppressor cells

    Science.gov (United States)

    Payne, Kyle K; Zoon, Christine K; Wan, Wen; Marlar, Khin; Keim, Rebecca C; Kenari, Mehrab Nasiri; Kazim, A Latif; Bear, Harry D; Manjili, Masoud H

    2016-01-01

    Two major barriers in the immunotherapy of breast cancer include tumor-induced immune suppression and the establishment of long-lasting immune responses against the tumor. Recently, we demonstrated in an animal model of breast carcinoma that expanding and reprogramming tumor-sensitized lymphocytes, ex vivo, yielded T memory (Tm) cells as well as activated CD25+ NKT cells and NK cells. The presence of activated CD25+ NKT and NK cells rendered reprogrammed T cells resistant to MDSC-mediated suppression, and adoptive cellular therapy (ACT) of reprogrammed lymphocytes protected the host from tumor development and relapse. Here, we performed a pilot study to determine the clinical applicability of our protocol using peripheral blood mononuclear cells (PBMCs) of breast cancer patients, ex vivo. We show that bryostatin 1 and ionomycin (B/I) combined with IL-2, IL-7 and IL-15 can expand and reprogram tumor-sensitized PBMCs. Reprogrammed lymphocytes contained activated CD25+ NKT and NK cells as well as Tm cells and displayed enhanced reactivity against HER-2/neu in the presence of MDSCs. The presence of activated NKT cells was highly correlated with the rescue of anti-HER-2/neu immune responses from MDSC suppression. Ex vivo blockade experiments suggest that the NKG2D pathway may play an important role in overcoming MDSC suppression. Our results show the feasibility of reprogramming tumor-sensitized immune cells, ex vivo, and provide rationale for ACT of breast cancer patients. PMID:24197563

  1. Netbaserede uddannelser og blended learning

    DEFF Research Database (Denmark)

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

    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...

  2. 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...

  3. 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.

  4. Soziale Pflegeversicherung grundlegend reformieren! Kritische Anmerkungen zum Gesetzentwurf der Bundesregierung vom 17.10.2007

    OpenAIRE

    Fichte, Damian

    2007-01-01

    Mitte Oktober hat die Bundesregierung einen Gesetzentwurf zur 'Weiterentwicklung' der Sozialen Pflegeversicherung (SPV) vorgelegt, der sich lediglich auf einige Änderungen innerhalb des bestehenden Systems beschränkt. Nach Ansicht des Instituts verfehlt der Gesetzentwurf das Ziel, die SPV auf eine langfristig tragfähige Basis zu stellen.

  5. 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......-IR supercontinuum source in other areas including infrared countermeasures....

  6. 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.

  7. Dicty_cDB: AFJ461 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available AF (Link to library) AFJ461 (Link to dictyBase) - - - Contig-U16405-1 AFJ461P (Link to Original ... lll*ntxs c*kiyr*kilkkkm*lksqityv*nkt Frame C: iwws*fpy *fh*ck*tfcc*r*fl*sif*l**yycnistrirki*vvl**nwg*sctif ...

  8. 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...

  9. 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.

  10. 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.

  11. 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...

  12. 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...

  13. Inhibition of Yin Yang 1-Dependent Repressor Activity of DR5 Transcription and Expression by the Novel Proteasome Inhibitor NPI-0052 Contributes to its TRAIL-Enhanced Apoptosis in Cancer Cells1

    OpenAIRE

    Baritaki, Stavroula; Suzuki, Eriko; Umezawa, Kazuo; Spandidos, Demetrios A.; Berenson, James; DANIELS, TRACY R.; Penichet, Manuel L; Jazirehi, Ali R; Palladino, Michael; Bonavida, Benjamin

    2008-01-01

    TRAIL promotes apoptotic tumor cell death; however, TRAIL-resistant tumors need to be sensitized to reverse resistance. Proteasome inhibitors potentiate TRAIL apoptosis in vitro and in vivo and correlate with up-regulation of death receptor 5 (DR5) via an unknown mechanism. We hypothesized that the proteasome inhibitor NPI-0052 inhibits the transcription repressor Yin Yang 1 (YY1) which regulates TRAIL resistance and negatively regulates DR5 transcription. Treatment of PC-3 and Ramos cells wi...

  14. 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

  15. 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

  16. 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; Tvede, Michael; Petersen, Janne; Eugen-Olsen, Jesper; Larsen, Klaus

    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 diagnostic...

  17. IFN-α suppresses GATA3 transcription from a distal exon and promotes H3K27 tri-methylation of the CNS-1 enhancer in human Th2 cells1

    OpenAIRE

    Huber, Jonathan P.; Gonzales-van Horn, Sarah R.; Roybal, Kole T.; Gill, Michelle A.; Farrar, J. David

    2014-01-01

    CD4+ T helper type 2 (Th2) development is regulated by the zinc finger transcription factor GATA3. Once induced by acute priming signals, such as IL-4, GATA3 poises the Th2 cytokine locus for rapid activation and establishes a positive feedback loop that maintains elevated GATA3 expression. Type I interferon (IFN-α/β) inhibits Th2 cells by blocking the expression of GATA3 during Th2 development and in fully committed Th2 cells. In this study, we have uncovered a unique mechanism by which IFN-...

  18. 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

  19. Computer simulation of aerosol dynamics with a unified agglomeration kernel

    International Nuclear Information System (INIS)

    Aerosol dynamics have been simulated with the computer code CONTAIN using a modified agglomeration kernel. The time (t) evolution of the size distribution (nk(t)) and the suspended mass concentration of particles of size index k was calculated for both the new kernel and the standard superposition kernel. In addition, the fractal nature of the particle geometry has been accounted for and the implications on the distributions are discussed. (author)

  20. 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...

  1. 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.

  2. 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...

  3. 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...

  4. Bronchoalveolar Immunologic Profile of Acute Human Lung Transplant Allograft Rejection

    OpenAIRE

    Gregson, Aric L.; Hoji, Aki; Saggar, Rajan; Ross, David J; Kubak, Bernard M; Jamieson, Beth D.; Weigt, S. Samuel; Lynch, Joseph P.; Ardehali, Abbas; Belperio, John A.; Yang, Otto O

    2008-01-01

    Bronchoalveolar lavage fluid (BALF) offers a potential means to diagnose acute rejection and could provide insight into the immune mechanisms responsible for lung allograft rejection. Transbronchial biopsies from 29 bronchoscopic procedures were assessed for rejection. Concurrent BALF lymphocyte subsets were examined by flow cytometry, including CD4+ and CD8+ T cells and their activation status via CD38 expression, NK, NK-like T (NT), B, T regulatory (Treg) and invariant receptor NK-T cells (...

  5. 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 ...

  6. Qualitätsstandards für die Online-Beratung

    Directory of Open Access Journals (Sweden)

    Birgit Knatz

    2006-03-01

    Full Text Available Online-Beratung hat sich seit mehr als zehn Jahren bewährt. Nun ist es an der Zeit, dass für die verschiedenen Beratungsbereiche gemeinsame Mindeststandards zu entwickeln, die für Online-Beratung maßgebend sind. Wirksame Qualitätsstandards sollten dabei nicht nur auf einzelne Aspekte beschränkt sein, sondern die Online-Beratung insgesamt einschließlich der notwendigen Rahmenbedingungen in den Blick nehmen.

  7. Entwicklung einer Suchmaschine für wissenschaftliche Dokumente

    OpenAIRE

    Pakula, Peter

    2009-01-01

    Hohe Investitionen und lange Entwicklungszyklen in der Luft- und Raumfahrt erfordern eine gewisse Sensibilität beim Umgang mit digitalem Wissen aus den beteiligten Bereichen. Zwar ist es in der Luft- und Raumfahrtforschung genauso wie in anderen Forschungsgebieten unverzichtbar, Neuerungen regelmäßig zu veröffentlichen und in der Fachwelt zur Diskussion zu stellen, hohe internationale Konkurrenz verhindert jedoch, dass interne Dokumentationen unbeschränkt zur Verfügung gestellt werden können....

  8. 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...

  9. Zur Harmonisierung des Rechts der Unternehmensübernahmen in der EG

    OpenAIRE

    Baums, Theodor

    1995-01-01

    Die Kommission plant seit langem eine Harmonisierung des Rechts der Unternehmensübernahmen in der Gemeinschaft. Betroffen von diesen Plänen sind freilich vorerst nur Aktiengesellschaften, deren Papiere an einem regulierten Markt gehandelt werden. Und noch in einer anderen Richtung sind die Regulierungspläne beschränkt: Der von der Kommission vorgelegte Vorschlag für eine dreizehnte Richtlinie des Rates auf dem Gebiete des Gesellschaftsrechts betrifft vornehmlich die Übernahme von Aktien einer...

  10. Entwicklung, klinische Verläufe, Auswirkungen und Behandlung von Funktionseinschränkungen und Deformitäten der Extremitäten bei Patienten mit proximalen spinalen Muskelatrophien

    OpenAIRE

    Kopschina, Carsten

    2010-01-01

    Hintergrund und Ziele Diese Arbeit beschäftigt sich mit der umfangreichen Problematik der Entwicklung, der klinischen Verläufe, der Auswirkungen und Behandlung von Funktionseinschränkungen und Deformitäten der Extremitäten bei Patienten mit proximalen spinalen Muskelatrophien. Das Spektrum der Publikationen zu diesem Thema in der Literatur ist eingeschränkt. In dieser Studie sollen diese Informationen zusammengefasst und mit eigener Erfahrung und Beobachtung unserer Patienten verglichen und d...

  11. Multimedia-Anbieter im Saarland

    OpenAIRE

    Matthäi, Ingrid; Schmidt, Gertrud

    1998-01-01

    Die kleinräumige Multimedia-Szene im Saarland beschränkt sich im wesentlichen auf drei Segmente: Softwarebranche, Internetprovider und multimediale Inhaltsanbieter sowie Call-Center. Gemessen an den Arbeitsplatzeffekten sind die Softwarebranche und die neu angesiedelten Call-Center die wichtigsten Wertschöpfungsbereiche. Die originären Multimedia-Produzenten setzen sich aus schon bestehenden kleinen Unternehmen der Werbe- und Medienbranche oder Neugründungen zusammen, deren quantitatives Verh...

  12. Wissenschaftliches Publizieren in Online-Zeitschriften: über das schwierige Vertrautwerden mit einem neuen Medium

    OpenAIRE

    Mruck, Katja; Mey, Günter

    2001-01-01

    "Mit dem Internet und seinen Medien gehen (potentiell) grundlegende Umbrüche für die Produktion, Distribution und Konsumtion wissenschaftlichen Wissens einher, wobei der vorliegende Beitrag sich auf den Stand und auf mögliche Determinanten der (Nicht-) Nutzung von Online-Journals durch Sozialwissenschaftler(innen) beschränkt. In dem vorliegenden Artikel werden neben einer kurzen Skizze technischer und struktureller Potenzen und Probleme und einer Übersicht über die aktuelle qualitative Online...

  13. Innate immune function in placenta and cord blood of hepatitis C--seropositive mother-infant dyads.

    Directory of Open Access Journals (Sweden)

    Christine Waasdorp Hurtado

    Full Text Available Vertical transmission accounts for the majority of pediatric cases of hepatitis C viral (HCV infection. In contrast to the adult population who develop persistent viremia in approximately 80% of cases following exposure, the rate of mother-to-child transmission (2-6% is strikingly low. Protection from vertical transmission likely requires the coordination of multiple components of the immune system. Placenta and decidua provide a direct connection between mother and infant. We hypothesized that innate immune responses would differ across the three compartments (decidua, placenta and cord blood and that hepatitis C exposure would modify innate immunity in these tissues. The study was comprised of HCV-infected and healthy control mother and infant pairs from whom cord blood, placenta and decidua were collected with isolation of mononuclear cells. Multiparameter flow cytometry was performed to assess the phenotype, intracellular cytokine production and cytotoxicity of the cells. In keeping with a model where the maternal-fetal interface provides antiviral protection, we found a gradient in proportional frequencies of NKT and gammadelta-T cells being higher in placenta than cord blood. Cytotoxicity of NK and NKT cells was enhanced in placenta and placental NKT cytotoxicity was further increased by HCV infection. HCV exposure had multiple effects on innate cells including a decrease in activation markers (CD69, TRAIL and NKp44 on NK cells and a decrease in plasmacytoid dendritic cells in both placenta and cord blood of exposed infants. In summary, the placenta represents an active innate immunological organ that provides antiviral protection against HCV transmission in the majority of cases; the increased incidence in preterm labor previously described in HCV-seropositive mothers may be related to enhanced cytotoxicity of NKT cells.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. Die Rolle des Smartphones im Einkaufsalltag: Erkenntnisse aus einer qualitativen Nutzerstudie

    OpenAIRE

    Kaufmann, Katja

    2015-01-01

    "Der Beitrag befasst sich mit Mobile Shopping als alltäglicher Konsumpraktik und stellt Ergebnisse einer qualitativen Studie mit Smartphone-Nutzern vor, die ihr Gerät im Einkaufskontext verwenden. Anders als bei traditionellen Mobiltelefonen ist die Verwendung von Smartphones nicht auf soziale Interaktion beschränkt, weshalb sie als Mobile Media konzeptualisiert werden. Es zeigt sich, dass sich die identifizierten Praktiken im Umgang mit dem Smartphone im Einkaufskontext vier Funktionen zuord...

  19. Hydropsdiagnostik mit Tieftonmodulation von Distorsionsprodukt-Otoemissionen

    OpenAIRE

    Goßow-Müller-Hohenstein, Elmen

    2005-01-01

    Ein tieffrequenter lauter Suppressorton verlagert das Corti-Organ periodisch in Richtung Scala vestibuli und Scala tympani. Simultan registrierte DPOAE (Distorsionsprodukte otoakustischer Emissionen) werden in beiden Richtungen unterschiedlich supprimiert. Bei Vorliegen eines endolymphatischen Hydrops (EH) ist die Beweglichkeit der Basilarmembran eingeschränkt, so daß keine oder eine nur geringe Modulation des DPOAE-Pegels entstehen kann. In dieser Arbeit wird die diagnostische Aussagekraft v...

  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. 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) ...

  2. 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 ...

  3. 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...

  4. 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...

  5. 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 ...

  6. Aktivierung kommunaler Nachhaltigkeitspotentiale in den Bereichen Ernährung und Energiewirtschaft

    OpenAIRE

    Schmagold, Philipp

    2012-01-01

    Im Zuge dieser Arbeit werden die Entstehungszusammenhänge vorhandener und teilweise auch de facto genutzter Nachhaltigkeitspotentiale ausgewählter Gemeinden Nordhessens beleuchtet. Die Gemeinde als bürgernahste staatliche Verwaltungseinheit, welche aktiv auf das Verhalten von Menschen und Unternehmen Einfluss nehmen kann, endet dabei nicht an der verwaltungsrechtlichen und politischen Gemeindegrenze. Aus Gründen der Handhabbarkeit des Promotionsvorhabens beschränkt sich der Autor auf die getr...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. Studiengangsmodellierung - Ein implementierter Diskussionsansatz

    OpenAIRE

    Brune, Henning; Carolla, Marco; Spitta, Thorsten

    2013-01-01

    Dieses Papier skizziert das konzeptionelle Datenmodell einer Studiengangsmodellierung für Campus-Management-Systeme. Nach den ersten Pilotprojekten scheint dies ein Schlüsselproblem für die Standardisierung solcher Systeme zu sein. Das Modell beschränkt sich auf die Grunddaten von Studiengängen, wodurch prosaische Studienordnungen nicht berücksichtigt werden müssen. Die Darstellung erfolgt als Objektsicht mit Attributen und einer Beziehungssicht als UML Klassendiagramm. Vorhandene Implementie...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  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. 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...

  19. Fernerkundungs- und GIS-Analyse der Impaktstrukturen Strangways (N.T.) und Shoemaker (W.A,), Australien

    OpenAIRE

    Zumsprekel, H. (Heiko)

    2003-01-01

    Die komplexen Impaktstrukturen Strangways und Shoemaker (Australien) wurden mithilfe von Fernerkundung und Geländearbeiten untersucht. Der Aufbau einer GIS-Datenbank zielte auf den Vergleich der Impaktsignaturen in komplementären Daten. In der Strangways-Struktur (ca. 646 Ma) treten shatter cones und PDFs im granitoiden Basement auf. Reste von Impaktbrekzien, z.T. mit Schmelzanteil, sind auf wenige Aufschlüsse im Kern beschränkt. In der Shoemaker-Struktur (1630 Ma ?)sind keine Impaktite...

  20. Mehrskalige Belastungsregelung in der variantenreichen Serienfertigung von KMU

    OpenAIRE

    Kroß, Philipp

    2013-01-01

    Das Umfeld produzierender Unternehmen wird als turbulent bezeichnet. Demgegenüber steht eine begrenzte Anpassungsfähigkeit der Produktionsstrukturen. Deren Auslastung ist stets in einem Arbeitsbereich zu halten, der durch die Fixkosten und die Maximalkapazität nach unten und oben beschränkt ist. Neben der permanenten Anpassung ist es daher erforderlich in einem kontinuierlichen Prozess auch die kapazitive Belastung der Produktionsstrukturen gezielt zu beeinflussen und vermeidbare Verluste akt...

  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. 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...

  3. PEDF und seine Auswirkungen auf die Proliferation und Differenzierung von neuronalen Stammzellen in der Subventrikulärzone und im Hippocampus im adulten Nagergehirn

    OpenAIRE

    Ertl, Gerhard Michael

    2009-01-01

    Bis zum Ende des letzten Jahrhunderts war man sich in der Wissenschaft einig, dass der Prozess der Neurogenese im ZNS auf das Stadium der Embryogenese beschränkt sei. Seit einiger Zeit weiß man allerdings, dass sich v.a. in zwei Regionen des Gehirns, der Subventrikulärzone und dem Gyrus dentatus im Hippocampus, zeitlebens neue Neurone bilden. Für die Steuerung der Wachstumsrate, Migration und Diifferenzierung spielen Wachstumsfaktoren eine entscheidende Rolle. In dieser Arbeit untersuchten wi...

  4. Studien zur enantioselektiven Synthese des marinen Makrolactons (–)-Dictyostatin

    OpenAIRE

    Röhm, Hartmut

    2010-01-01

    Heute handelt es sich bei mehr als der Hälfte aller zugelassenen Arzneimittel um Naturstoffe, Naturstoffderivate oder Naturstoffanaloga. Die Suche nach neuen Leitstrukturen beschränkt sich nicht mehr nur auf terrestrische Pflanzen und Mikroorganismen, sondern vermehrt auf marine Organismen. Dabei sind vor allem fest am Meeresboden verwachsene Schwämme und Korallen sehr interessant, da sie sich nur durch Anpassung ihres Metabolitprofiles, das heißt die Biosynthese geeigneter Toxine, vor Feinde...

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Sexual dimorphism in the control of amebic liver abscess in a mouse model of disease.

    Science.gov (United States)

    Lotter, Hannelore; Jacobs, Thomas; Gaworski, Iris; Tannich, Egbert

    2006-01-01

    Amebic liver abscess (ALA) is the most common extraintestinal manifestation of human infection by the enteric protozoan parasite Entamoeba histolytica. In contrast to intestinal infection, ALA greatly predominates in males but is rare in females. Since humans are the only relevant host for E. histolytica, experimental studies concerning this sexual dimorphism have been hampered by the lack of a suitable animal model. By serial liver passage of cultured E. histolytica trophozoites in gerbils and mice, we generated amebae which reproducibly induce ALA in C57BL/6 mice. Interestingly, all animals developed ALA, but the time courses of abscess formation differed significantly between the genders. Female mice were able to clear the infection within 3 days, whereas in male mice the parasite could be recovered for at least 14 days. Accordingly, male mice showed a prolonged time of recovery from ALA. Immunohistology of abscesses revealed that polymorphonuclear leukocytes and macrophages were the dominant infiltrates, but in addition, gamma,delta-T cells, NK cells, and natural killer T (NKT) cells were also present at early times during abscess development, whereas conventional alpha,beta-T cells appeared later, when female mice had already cleared the parasite. Interestingly, male and female mice differed in early cytokine production in response to ameba infection. Enzyme-linked immunospot assays performed with spleen cells of infected animals revealed significantly higher numbers of interleukin-4-producing cells in male mice but significantly higher numbers of gamma interferon (IFN-gamma)-producing cells in female mice. Early IFN-gamma production and the presence of functional NKT cells were found to be important for the control of hepatic amebiasis as application of an IFN-gamma-neutralizing monoclonal antibody or the use of NKT knockout mice (Valpha14iNKT, Jalpha 18(-/-)) dramatically increased the size of ALA in female mice. In addition, E. histolytica trophozoites

  12. 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

  13. Spleen-resident CD4+ and CD4- CD8α- dendritic cell subsets differ in their ability to prime invariant natural killer T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Emilie Bialecki

    Full Text Available One important function of conventional dendritic cells (cDC is their high capacity to capture, process and present Ag to T lymphocytes. Mouse splenic cDC subtypes, including CD8α(+ and CD8α(- cDC, are not identical in their Ag presenting and T cell priming functions. Surprisingly, few studies have reported functional differences between CD4(- and CD4(+ CD8α(- cDC subsets. We show that, when loaded in vitro with OVA peptide or whole protein, and in steady-state conditions, splenic CD4(- and CD4(+ cDC are equivalent in their capacity to prime and direct CD4(+ and CD8(+ T cell differentiation. In contrast, in response to α-galactosylceramide (α-GalCer, CD4(- and CD4(+ cDC differentially activate invariant Natural Killer T (iNKT cells, a population of lipid-reactive non-conventional T lymphocytes. Both cDC subsets equally take up α-GalCer in vitro and in vivo to stimulate the iNKT hybridoma DN32.D3, the activation of which depends solely on TCR triggering. On the other hand, and relative to their CD4(+ counterparts, CD4(- cDC more efficiently stimulate primary iNKT cells, a phenomenon likely due to differential production of co-factors (including IL-12 by cDC. Our data reveal a novel functional difference between splenic CD4(+ and CD4(- cDC subsets that may be important in immune responses.

  14. 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

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

    Science.gov (United States)

    Oliveira, Fabrício M S; Horta, Bernardo C; Prata, Luana O; Santiago, Andrezza F; Alves, Andréa C; Faria, Ana M C; Gomes, Maria A; Caliari, Marcelo V

    2012-04-27

    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, non-infected (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. PMID:24470941

  16. 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

  17. 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.

  18. 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.

  19. 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...

  20. 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...

  1. Tribologische Untersuchungen am Förderzahnriemen

    OpenAIRE

    Nendel, Klaus; Kaden, Hendrik

    2007-01-01

    Zahnriemenfördersysteme haben auf Grund ihrer wirtschaftlichen und technischen Vorteile beim Transport von Stückgütern ein breites Anwendungsfeld in den unterschiedlichen Bereichen der Industrie gefunden und gewinnen weiterhin an Bedeutung. Die Auslegung der Systeme beschränkt sich gegenwärtig im Wesentlichen auf die Zugstrang- und die Zahnfußfestigkeit des Zahnriemens. Grundlagen der Berechnungen sind oft recht vage Aussagen zur Höhe des Reibwertes zwischen dem Zahnriemen und dessen Stützsch...

  2. Rice Price Controls Policy of Vietnam and its competition with Thailand

    OpenAIRE

    Pham, Thi Huong Diu

    2015-01-01

    Vietnam und Thailand sind zwei der führenden Exporteure für Reis. Zurzeit hat die staatliche Preispolitik den stärksten und meisten Einfluss auf die vietnamesische Branche für Reis. Es beschränkt die Exportmenge, um die Menge für den nationalen Nahrungsmittelbedarf sicherzustellen. Diese Regulierung hält die vietnamesische Produktion unter ihrem vollständigen potenzial, im Vergleich zu der Reisproduktion in Thailand, zurück. Viele Experten unterstellen, dass Vietnam mehr Aufmerksamkeit der na...

  3. 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...

  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. Konzeption und Implementierung eines Frameworks für spezialisierte Suchmaschinen

    OpenAIRE

    Arnold, Steffen

    1999-01-01

    Spezialisierte Suchmaschinen sind Suchmaschinen für das World Wide Web, die auf ein Themengebiet beschränkt und zugeschnitten sind. Dadurch sind sie in der Lage, wesentlich genauere Ergebnisse auf Suchanfragen zu ermitteln, als dies universellen Suchmaschinen möglich ist. Das Konzept der Domänen-Experten ist ein an der Fakultät Informatik der Universität Stuttgart entwickeltes Konzept für spezialisierte Suchmaschinen. Wesentlich für die Praxistauglichkeit des Konzeptes ist ...

  6. Die Gründung einer Europäischen Aktiengesellschaft durch Verschmelzung und das nationale Recht

    OpenAIRE

    Fuchs, Mirjam

    2002-01-01

    Die Verordnung über das Statut der Europäischen (Aktien-)Gesellschaft (SE) beschränkt sich darauf, die Kernbereiche dieser europäischen Rechtsform zu regeln, und verweist im übrigen auf das nationale Recht. Die Arbeit widmet sich rechtlichen Fragen, die sich aus der Konzeption der Verordnung als Rahmenregelung ergeben. Anhand der Gründung einer SE durch Verschmelzung wird untersucht, wie sich SE-Verordnung und nationales Recht gegenseitig beeinflussen und ergänzen. Im Mittelpunkt steht die Fr...

  7. "Rückerwerb eigener Aktien und WpÜG"

    OpenAIRE

    Baums, Theodor; Stöcker, Mathias

    2002-01-01

    Das am 01.01.2002 in Kraft getretene Gesetz zur Regelung von öffentlichen Angeboten zum Erwerb von Wertpapieren und von Unternehmensübernahmen (WpÜG) beschränkt sich - anders als noch der Diskussionsentwurf des WpÜG - nicht auf die Regelung von öffentlichen Angeboten zum Erwerb von Wertpapieren, die auf den Erwerb der Kontrolle an einer Zielgesellschaft gerichtet sind oder eine bereits bestehende Kontrollmehrheit voraussetzen, sondern trifft darüber hinaus mit den §§ 10 - 28 WpÜG Bestimmungen...

  8. Pulvermetallurgische Funktionsbauteile aus NiTi- und NiTi-X Legierungspulvern

    OpenAIRE

    Bitzer, Martin

    2014-01-01

    Die Pulvermetallurgie (P/M) ist eine vielversprechende Verfahrenstechnik für die Herstellung von NiTi-Bauteilen, die aufgrund des Formgedächtniseffekts nur eingeschränkt spanend bearbeitet werden können. Eine industrielle Umsetzung pulvermetallurgischer Methoden ist jedoch nicht trivial, da das Phasenumwandlungsverhalten der Legierung während der Prozessführung durch O- und C-Aufnahme sowie Ausscheidung von Ni4Ti3 beeinflusst wird. In der vorliegenden Arbeit wird jeder Schritt der P/M-Prozess...

  9. 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...

  10. Callcenter: Mitarbeiterkontrollen auf dem datenschutzrechtlichen Prüfstand

    OpenAIRE

    Hoss, Dennis

    2010-01-01

    Callcenter spielen in der heutigen Zeit eine bedeutende Rolle in der Kundenkommunikation. Für die Betreiber der Callcenter ist dabei der Umgang mit Kundendaten selbstverständlich; dasselbe gilt oftmals in Bezug auf die Daten ihrer Mitarbeiter, die bei der Telekommunikation anfallen. Das Persönlichkeitsrecht der Arbeitnehmer schränkt den zulässigen Umgang mit solchen Daten jedoch stark ein. Der vorliegende Beitrag behandelt – insbesondere unter Berücksichtigung des seit 1. September 2009 gelte...

  11. 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...

  12. 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...

  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. 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...

  15. Lichtauskopplung aus LEDs mittels Metallnanoteilchen

    OpenAIRE

    Göhler, Tino

    2011-01-01

    Der externe Wirkungsquerschnitt von auf AlGaAs/InGaAlP basierenden Leuchtdioden (LEDs) ist auf Grund von Totalreflexion infolge des hohen Brechungsindex des Halbleitermaterials (n=3...4) beschränkt. Auf die Oberfläche der LED aufgebrachte metallische Nanoteilchen (MNT) können jedoch als Dipolstreuer genutzt werden, um so die Emission der LED zu vergrößern. In dieser Arbeit wurden zunächst einzelne Goldnanoteilchen verschiedener Größe auf einer solchen Leuchtdiode in zwei verschiedenen Der ext...

  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. Therapy for minimal residual tumour disease: beta-galactosylceramide inhibits growth of recurrent HPV16-associated neoplasms after surgery and chemotherapy

    Czech Academy of Sciences Publication Activity Database

    Šímová, Jana; Indrová, Marie; Bieblová, Jana; Mikyšková, Romana; Bubeník, Jan; Reiniš, Milan

    2010-01-01

    Roč. 126, č. 12 (2010), s. 2997-3004. ISSN 0020-7136 R&D Projects: GA ČR GA301/06/0774; GA AV ČR IAA500520807; GA ČR GA301/07/1410; GA ČR GA301/09/1024 EU Projects: European Commission(XE) 18933 - CLINIGENE Institutional research plan: CEZ:AV0Z50520514 Keywords : beta-galactosylceramide * tumour immunotherapy * NKT cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.926, year: 2010

  18. 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....

  19. 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...

  20. Zur Identitätspolitik Qualitativer Forschung. Ein diskursanalytischer Inter-Text

    OpenAIRE

    Nentwich, Julia C.; Dey, Pascal

    2006-01-01

    Unser Beitrag versteht sich als Inter-Text zwischen ausgewählten FQS-Artikeln – welche in der einen oder anderen Art die Identitätspolitik qualitativer Forschung zum Ausdruck bringt – und der breit angelegten Qualitätsdiskussion sozialwissenschaftlicher Forschung. Anhand einer Diskursanalyse wird untersucht, wie die Bedeutung "qualitativer Forschung" durch deren Verknüpfung mit dem positivistischen Verständnis von Forschung eingeschränkt wird. Das Ziel dabei ist, zwei besonders rigide binäre ...

  1. 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...

  2. 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

  3. 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.

  4. Bodenbelastung und Bodenbeanspruchung unterschiedlicher Fahrwerkskonfigurationen

    OpenAIRE

    Geischeder, Rupert

    2011-01-01

    Zunehmende Fahrzeugmassen erhöhen das Risiko der Bodenverdichtung. Widersprüchliche Aussagen zur Wirkung von Rad- und Raupenlaufwerken auf den Ackerboden können nicht uneingeschränkt zugestimmt werden. Ein systematischer Versuch sollte dies klären. Es wurde die Wirkung von Rad- und Raupenfahrwerke bei annähernd gleichem Kontaktflächendruck und etwa gleich hoher Gesamtlast untersucht. Das Raupenlaufwerk mit 113 kN Last erzeugte bei der dynamischen Druckmessung geringere Bodendrücke, die sich ü...

  5. 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...

  6. 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

  7. Einstellungen zum Rauchverbot in der Europäischen Union : eine komparative Analyse der 27 Mitgliedsländer der EU mit Umfragedaten des Eurobarometers

    OpenAIRE

    Haker, Kristin 

    2008-01-01

    "In diesem Artikel wird gefragt, wie die Bürger der EU gegenüber einem Rauchverbot eingestellt sind und welche Faktoren ihre Einstellung erklären können. In einem ersten Schritt wird die EU-Raucherpolitik rekonstruiert und gezeigt, welche Maßnahmen die Europäische Union in der Vergangenheit bereits ergriffen hat, um den Nichtraucherschutz in ihren Mitgliedsländern zu gewährleisten. Hier schränkt vor allem das geltende Subsidiaritätsprinzip die Handlungsmöglichkeiten der EU ein. Anschließend w...

  8. 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...

  9. 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...

  10. Strategien für die Melissezüchtung (Melissa officinalis

    Directory of Open Access Journals (Sweden)

    Kittler, Johannes

    2014-09-01

    Full Text Available Es wurden 120 Melisseherkünfte in Feldversuchen evaluiert. In diesem Material wurde die Variabilität für Winterhärte, Gehalt und Zsammensetzung des ätherischen Öls, Rosmarinsäuregehalt und eingeschränkt Blattertrag beschrieben. Die beschriebene Variabilität ermöglichte die Entwicklung homozygoter Linien mit hoher Eigenleistung für die genannten Zuchtziele bis zur I4-Inzuchtgeneration. Die Kreuzung definierter Linien ermöglichte die Schaffung eines neuen Genpools als Ausgansmaterial für die Entwicklung weiterer aussichtsreicher Linien.

  11. 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 ...

  12. Gefährliche Tiere in Menschenhand

    OpenAIRE

    Beckstein, Ruth

    2009-01-01

    Die private Hobbytierhaltung ist nicht auf Haushunde, Katzen und klassische Heimtiere wie Kleinnager, Ziervögel oder Zierfische beschränkt. Die Haltung von Wildtieren, insbesondere von exotischen Reptilien, in Privathand hat längst nennenswerte Bedeutung erreicht. Auch Wildtiere, von denen beträchtliche Gefahren für den Menschen ausgehen können, werden privat gehalten. Genaue Zahlen sind mangels Meldepflicht nicht verfügbar. Obgleich auch keine genauen Unfallzahlen bekannt sind, darf das mit ...

  13. 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...

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Die andere Geschichte. Quellen zur Geschlechtergeschichte aus drei Jahrtausenden

    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.

  19. 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

    2016-01-01

    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

  20. 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.

  1. Candida albicans up-regulates the Fas-L expression in liver Natural Killer and Natural Killer T cells.

    Science.gov (United States)

    Renna, María Sol; Figueredo, Carlos Mauricio; Rodríguez-Galán, María Cecilia; Icely, Paula Alejandra; Cejas, Hugo; Cano, Roxana; Correa, Silvia Graciela; Sotomayor, Claudia Elena

    2015-11-01

    After Candida albicans arrival to the liver, the local production of proinflammatory cytokines and the expanded intrahepatic lymphocytes (IHL) can be either beneficial or detrimental to the host. Herein we explored the balance between protective inflammatory reaction and liver damage, focusing our study on the contribution of TNF-α and Fas-Fas-L pathways in the hepatocellular apoptosis associated to C. albicans infection. A robust tissue reaction and a progressive increase of IL-1β, IL-6 and TNF-α were observed in infected animals. Blocking the biological activity of TNF-α did not modify the number of apoptotic cells observed in C. albicans infected animals. Fas-L molecule was up regulated on purified hepatic mononuclear cells and its expression progressed with the infection. In the IHL compartment, the absolute number of Fas-L+ NK and NKT cells increased on days 1 and 3 of the infection. C. albicans was also able to up regulate Fas-L expression in normal liver NK and NKT cells after in vitro contact. The innate receptor TLR2 was involved in this phenomenon. In the interplay between host factors and evasion strategies exploited by pathogens, the mechanism supported here could represent an additional way that allows this fungus to circumvent protective immune responses in the liver. PMID:26101139

  2. 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

  3. 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

  4. 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.

  5. 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

  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. 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.

  9. 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.

  10. Immunological changes in different patient populations with chronic hepatitis C virus infection

    Science.gov (United States)

    Szereday, Laszlo; Meggyes, Matyas; Halasz, Melinda; Szekeres-Bartho, Julia; Par, Alajos; Par, Gabriella

    2016-01-01

    AIM: To investigate killer inhibitory and activating receptor expression by natural killer (NK), natural killer T-like (NKT-like) and CD8+ T lymphocytes in patients with chronic hepatitis C virus (HCV) infection with elevated and with persistently normal alanine aminotransferase (PNALT). METHODS: The percentage of peripheral blood Treg cells, KIR2DL3, ILT-2, KIR3DL1, CD160, NKG2D, NKG2C expressing NK, T and NKT-like cells, cytokine production and NK cytotoxicity were determined by flow cytometry. Twenty-one patients with chronic HCV infection with elevated alanine aminotransferase, 11 HCV carriers with persistently normal alanine aminotransferase and 15 healthy volunteers were enrolled. RESULTS: No significant differences were observed in the percentage of total T, NK or NKT-like cells between study groups. Comparing the activating and inhibitory receptor expression by NK cells obtained from HCV carriers with PNALT and chronic HCV hepatitis patients with elevated alanine aminotransferase, NKG2D activating receptor expression was the only receptor showing a significant difference. NKG2D expression of NK cells was significantly lower in patients with elevated alanine aminotransferase. The expression of CD160, NKG2D and NKG2C activating receptor by CD8+ T cells were significantly lower in patients with chronic HCV hepatitis than in healthy controls and in HCV carriers with PNALT. Plasma TGF-β1 levels inversely correlated with NKG2D expression by NK cells. In vitroTGF-β1 treatment inhibited NK cells cytotoxic activity and downregulated NKG2D expression. CD8+ T cells from HCV carriers with PNALT showed significantly elevated expression of CD160, NKG2D and NKG2C activating receptors compared to chronic HCV patients with elevated alanine aminotransferase. Enhanced expression of inhibitory KIR2DL3 receptor, and decreased ILT-2 expression on NK cells were also found in chronic hepatitis C patients compared to healthy controls. CONCLUSION: Our study demonstrated a complex

  11. Lung CD8+ T cells in COPD have increased expression of bacterial TLRs

    Directory of Open Access Journals (Sweden)

    Freeman Christine M

    2013-02-01

    Full Text Available Abstract Background Toll-like receptors (TLRs on T cells can modulate their responses, however, the extent and significance of TLR expression by lung T cells, NK cells, or NKT cells in chronic obstructive pulmonary disease (COPD is unknown. Methods Lung tissue collected from clinically-indicated resections (n = 34 was used either: (a to compare the expression of TLR1, TLR2, TLR2/1, TLR3, TLR4, TLR5, TLR6 and TLR9 on lung CD8+ T cells, CD4+ T cells, NK cells and NKT cells from smokers with or without COPD; or (b to isolate CD8+ T cells for culture with anti-CD3ε without or with various TLR ligands. We measured protein expression of IFN-γ, TNF-α, IL-13, perforin, granzyme A, granzyme B, soluble FasL, CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL9 in supernatants. Results All the lung subsets analyzed demonstrated low levels of specific TLR expression, but the percentage of CD8+ T cells expressing TLR1, TLR2, TLR4, TLR6 and TLR2/1 was significantly increased in COPD subjects relative to those without COPD. In contrast, from the same subjects, only TLR2/1 and TLR2 on lung CD4+ T cells and CD8+ NKT cells, respectively, showed a significant increase in COPD and there was no difference in TLR expression on lung CD56+ NK cells. Production of the Tc1 cytokines IFN-γ and TNF-α by lung CD8+ T cells were significantly increased via co-stimulation by Pam3CSK4, a specific TLR2/1 ligand, but not by other agonists. Furthermore, this increase in cytokine production was specific to lung CD8+ T cells from patients with COPD as compared to lung CD8+ T cells from smokers without COPD. Conclusions These data suggest that as lung function worsens in COPD, the auto-aggressive behavior of lung CD8+ T cells could increase in response to microbial TLR ligands, specifically ligands against TLR2/1.

  12. 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...

  13. Energioptimering för Recip Strängnäs AB

    OpenAIRE

    Lindholm, Tobias

    2008-01-01

    Recip Strängnäs AB är ett miljöcertifierat företag som framställer och förpackar penicillin produkter. Företaget måste göra vissa reparationer på ett av ventilationssystemen. De tar tillfället i akt att gå igenom energiomsättningen i helhet då åtgärder redan måste göras. På grund av det ökade oljepriset och mer fokus på miljön är det intressant att byta ut denna energikälla som används idag, vilket är ånga som produceras genom eldning av olja. Den energikälla som är tänkt att ersätta ångan är...

  14. Rezension zu: Gabriele Winker, Nina Degele: Intersektionalität. Zur Analyse sozialer Ungleichheiten. Bielefeld: transcript Verlag 2009.

    Directory of Open Access Journals (Sweden)

    Heike Kahlert

    2010-02-01

    Full Text Available Gabriele Winker und Nina Degele legen mit ihrer kompakten Monographie erstmals für den deutschsprachigen Raum eine in Theorie, Methodologie und Empirie stringente eigenständige Abhandlung zur intersektionalen Analyse von sozialen Ungleichheiten vor. Das in jeder Hinsicht übersichtlich gestaltete Buch besticht durch eine begründete Argumentation, insbesondere in Bezug auf die theoretischen Vorentscheidungen, durch eine klare Gliederung und vor allem durch die Schritt für Schritt nachvollziehbare Umsetzung des vorgeschlagenen theoretischen und methodologischen Rahmens in die empirische Sozialforschung. Es ist daher uneingeschränkt empfehlenswert, auch für den Einsatz in der Hochschullehre, und es ist von hohem Anregungspotential für die wissenschaftliche Weiterentwicklung intersektionaler Analysen von sozialen Ungleichheiten.

  15. En resa bland planeterna med Lova, Melker och Pixi. : Ett undervisningsmaterial inom astronomi för årskurs ett till tre.

    OpenAIRE

    Krause, Marta; Larsson, Amanda

    2013-01-01

    Vi har under vår verksamhetsförlagda utbildning, utifrån egna erfarenheter och genom att läsa forskning fått en förståelse för att barns föreställningar om naturvetenskapliga fenomen inte stämmer överens med verkligheten. Det har också gett oss en uppfattning om att det saknas läromedel inom astronomi för barn i de yngre åldrarna. Grundat utifrån detta valde vi att utveckla ett läromedel inom astronomi. Läromedlet är tänkt att vara lättillgängligt och lättanvänt för lärare, samt att läromedle...

  16. 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.

  17. I Am Cait och Keeping Up with the Kardashians; manifestation av en kvinnlig identitet.

    OpenAIRE

    Granvik, Hanna

    2016-01-01

    Den olympiska medaljören och reality-TV kändisen Bruce Jenner valde att öppet inför världen år 2015 tala om sin könsidentitet där han identifierar sig själv mer som en kvinna än en man och att han tänkt leva resten av sitt liv som kvinna. Bruce Jenners transformation till Caitlyn Jenner har hyllats världen över och i realityserien I Am Cait får vi följa början på hennes liv som ”nybliven” kvinna och transperson. Tidigare, som Bruce Jenner, figurerade han i realityserien Keeping Up with the Ka...

  18. Cytodiagnosis of extranodal natural killer/T-cell lymphoma, nasal type: Report of two cases

    Directory of Open Access Journals (Sweden)

    Kavita Mardi

    2014-01-01

    Full Text Available Extranodal natural killer (NK/T-cell lymphoma, nasal type (NK/T is relatively rare, associated with aggressive behavior and poor prognosis. Histopathological findings, immunohistochemical study, and Epstein-Barr virus-encoded ribonucleic acid in situ hybridization are essential for the diagnosis. There are a few case reports in the literature describing the cytological findings of these uncommon lymphomas. We herein describe cytological findings in two cases of extranodal NK/T-cell lymphoma, nasal type presenting as lacrimal gland and/or nasal masses. Fine-needle aspiration smears revealed small to medium-sized lymphoid cells showing irregular nuclear outline, moderate amounts of light basophilic cytoplasm containing fine azurophilic granules in most of the cells. Some of these atypical lymphoid cells showed tongue-like projections of cytoplasm from one or both sides of the cells. Histopathological examination revealed typical angoicentric, angiodestructive growth pattern of these lymphomas.

  19. 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 ...

  20. 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...

  1. ”Lämna tistlarna kvar!?” : Om att ta lärande till hjälp för att lyckas gå från ord till praktisk handling i organisationens interna kommunikation.

    OpenAIRE

    Wiklander, Marianne

    2013-01-01

    Utgångspunkten i uppsatsen är, att om en kommunikation av ett budskap inom en organisation skall ha förutsättningar att lyckas, måste budskapet: 1. först och främst bli mottaget, d v s uppfattas av en tänkt mottagare. 2. därefter tolkas korrekt, d v s avsändarens och mottagarens förståelse måste stämma överens. 3. sist, men inte minst, väcka engagemang, d v s vilja att ta till sig budskapet, samt skapa självförtroende, d v s tro att kunna omsätta budskapet i praktiken. Tre metoder analyseras ...

  2. Hur väl lämpad är Moraån som livsmiljö för havsöring?

    OpenAIRE

    Widström, Karin

    2013-01-01

    En meandrande å är en miljötyp som bidrar till hög biologisk mångfald. I många fall har dessapåverkats av människan genom uträtning och uppdämning av det flödande vattnet, vilket harsänkt de biologiska värdena. Sedan 1980-talet har det funnits planer på att göra en del av denmeandrande Moraån i Södertälje till ett naturreservat. Då samlad, detaljerad dokumentationom området saknades och ån är utpekad som ett särskilt känsligt område med hänsyn tillhavsöring och dess reproduktion i Stockholms ...

  3. 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.

  4. 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...

  5. 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...

  6. Ressourceneinsatzplanung In der Energie- und Verfahrenstechnik

    Science.gov (United States)

    Engell, Sebastian; Handschin, Edmund; Rehtanz, Christian; Schultz, Rüdiger

    Der ökologisch nachhaltige, wirtschaftlich effiziente und politisch faire Umgang mit den Ressourcen der Erde ist eine der größten Herausforderungen an die Menschheit im 21. Jahrhundert und impliziert Paradigmenwechsel in allen Bereichen des gesellschaftlichen Lebens. Energie- und Verfahrenstechnik sind traditionell Bereiche, in denen der optimale Umgang mit kostbaren und beschränkt verfügbaren Ressourcen von erstrangiger Bedeutung ist. Zur Lösung der damit verbundenen komplexen Entscheidungsprobleme sind mathematische Methoden schon seit längerem im Einsatz. Hierbei können aber noch längst nicht alle bislang aufgetretenen Probleme fundiert angegangen werden. Der wachsende wirtschaftliche und ökologische Druck auf die Effizienz der Produktions-und Versorgungssysteme sowie stärkere Schwankungen von Angebot und Nachfrage führen zu neuen Herausforderungen, für die neue mathematische Methoden und Algorithmen entwickelt werden müssen.

  7. 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)

  8. 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

  9. 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...

  10. 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...

  11. 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.

  12. 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...

  13. Cernunnos deficiency reduces thymocyte life span and alters the T cell repertoire in mice and humans.

    Science.gov (United States)

    Vera, Gabriella; Rivera-Munoz, Paola; Abramowski, Vincent; Malivert, Laurent; Lim, Annick; Bole-Feysot, Christine; Martin, Christelle; Florkin, Benoit; Latour, Sylvain; Revy, Patrick; de Villartay, Jean-Pierre

    2013-02-01

    Cernunnos is a DNA repair factor of the nonhomologous end-joining machinery. Its deficiency in humans causes radiosensitive severe combined immune deficiency (SCID) with microcephaly, characterized in part by a profound lymphopenia. In contrast to the human condition, the immune system of Cernunnos knockout (KO) mice is not overwhelmingly affected. In particular, Cernunnos is dispensable during V(D)J recombination in lymphoid cells. Nevertheless, the viability of thymocytes is reduced in Cernunnos KO mice, owing to the chronic activation of a P53-dependent DNA damage response. This translates into a qualitative alteration of the T cell repertoire to one in which the most distal Vα and Jα segments are missing. This results in the contraction of discrete T cell populations, such as invariant natural killer T (iNKT) and mucosa-associated invariant T (MAIT) cells, in both humans and mice. PMID:23207905

  14. 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.

  15. 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.

  16. Modulare LDAP-Server-, -Protokoll und - Funktionserweiterungen am Beispiel von OpenLDAP

    Science.gov (United States)

    Pluta, Daniel

    In diesem Artikel wird ein Standardisierungsvorschlag für eine LDAP-Protokollerweiterung und deren Referenzimplementierung in Form einer modularen Erweiterung für die LDAP-Software-Suite des OpenLDAPProjektes vorgestellt. Nach einer Einführung in und einem Überblick über die wichtigsten OpenLDAP-Komponenten stellen wir unseren Lösungsansatz vor und gehen auf seine technischen Details ein. Ziel dieses Overlays ist die Implementierung einer neuen Funktionalität, die vom LDAP-Protokoll bisher nicht vorgesehen ist: Der Umfang der Suchergebnismenge soll serverseitig, dezentral und in der Granularität ganzer Objekte in Abhängigkeit von der aktuellen Serverzeit (konfigurierbar) eingeschränkt werden.

  17. Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens.

    Science.gov (United States)

    Holtzman, Michael J

    2012-08-01

    Research on the pathogenesis of asthma has traditionally concentrated on environmental stimuli, genetic susceptibilities, adaptive immune responses, and end-organ alterations (particularly in airway mucous cells and smooth muscle) as critical steps leading to disease. The focus of this cascade has been the response to allergic stimuli. An alternative scheme suggests that respiratory viruses and the consequent response of the innate immune system also drives the development of asthma as well as related inflammatory diseases. This conceptual shift raises the possibility that sentinel cells such as airway epithelial cells, DCs, NKT cells, innate lymphoid cells, and macrophages also represent critical components of asthma pathogenesis as well as new targets for therapeutic discovery. A particular challenge will be to understand and balance the innate as well as the adaptive immune responses to defend the host against acute infection as well as chronic inflammatory disease. PMID:22850884

  18. Determination of the main commercial components of the apatite ores in Khibiny using nuclear well logging

    International Nuclear Information System (INIS)

    Determination is carried out using a combination of well logging measurements including NAK-N16, NAK-Al28, GGK-P, NK-T and NK-N. Calibration procedures, stability control and the measurement regimes of the KazVIRG gamma-spectrometric equipment have been described. The reproduction of average values of NAK-N16 makes up 2-6%, NAK-Al28 -(2O5 determination is equal to that of the NAK-N16 readings; the reproduction error of Al2O3 and density determination is less than that of the NAK-Al28 and GGK-P reproduction. The paper presents interpretation methods along with the results of correlation of well logging data and core sampling for P2O5 and Al2O3. Examples of interpretation for different deposits have been given

  19. 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.

  20. The role of lipopeptidophosphoglycan in the immune response to Entamoeba histolytica.

    Science.gov (United States)

    Wong-Baeza, Isabel; Alcántara-Hernández, Marcela; Mancilla-Herrera, Ismael; Ramírez-Saldívar, Itzmel; Arriaga-Pizano, Lourdes; Ferat-Osorio, Eduardo; López-Macías, Constantino; Isibasi, Armando

    2010-01-01

    The sensing of Pathogen Associated Molecular Patterns (PAMPs) by innate immune receptors, such as Toll-like receptors (TLRs), is the first step in the inflammatory response to pathogens. Entamoeba histolytica, the etiological agent of amebiasis, has a surface molecule with the characteristics of a PAMP. This molecule, which was termed lipopeptidophosphoglycan (LPPG), is recognized through TLR2 and TLR4 and leads to the release of cytokines from human monocytes, macrophages, and dendritic cells; LPPG-activated dendritic cells have increased expression of costimulatory molecules. LPPG activates NKT cells in a CD1d-dependent manner, and this interaction limits amebic liver abscess development. LPPG also induces antibody production, and anti-LPPG antibodies prevent disease development in animal models of amebiasis. Because LPPG is recognized by both the innate and the adaptive immune system (it is a "Pamptigen"), it may be a good candidate to develop a vaccine against E. histolytica infection and an effective adjuvant. PMID:20145703

  1. Geobasisdaten für die Planung?

    Science.gov (United States)

    Zölitz-Möller, Reinhard

    2002-09-01

    Die Nutzer von Geobasisdaten der Vermessungs- und Katasterverwaltungen finden heute vor allem in ATKIS (Amtliches Topographisch-Kartographisches Informationssystem) und in der ALK (automatisiert geführte Liegenschaftskarte; hier noch eingeschränkt) flächendeckende und für eine Fachdatenintegration geeignete Geodatenbestände vor. Gleichwohl wird von Nutzerseite häufig ein differenziertes und in Teilen kritisches Bild gezeichnet. Die Kritik richtet sich v.a. auf die Probleme, die ATKIS-Anwender mit dem Nutzerkomfort, dem komplexen Datenmodell, unrichtigen Flächennutzungsangaben, inkompatiblen Objektdefinitionen, den Preisen sowie mangelnder Aktualität und Vollständigkeit haben. Dennoch gibt es für viele Zwecke auch in der Planung langfristig keine echte Alternative zu den Geobasisdaten.

  2. Fördomar mot arbetssökandens kön och namn vid intresseanmälan för en utannonserad tjänst.

    OpenAIRE

    Petersson, Maria

    2003-01-01

    Syftet med denna studie var att undersöka om arbetsgivare diskriminerar kvinnor och invandrare eller personer med utländsk bakgrund. Studien genomfördes med hjälp av ett frågeformulär som skapades för denna studie. Till frågeformuläret hörde brevet från en tänkt arbetssökande. Det fanns fyra alternativa namn: ett svenskt och ett utländskt mansnamn samt ett svenskt och ett utländskt kvinnonamn. Innehållet i brevet var för övrigt identiskt. Frågeformuläret innehöll dessutom två frågor som hade ...

  3. 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. Det...... amerikanske militær har været fødselshjælper for den nye teknologi. Herfra har serious games bredt sig til andre sektorer og og i-lande, inkl. Danmark. Bogen skildrer, hvordan det nye forretningsområde er i færd med at blive udkrystalliseret af en række beslægtede industrigrene, og hvordan udviklingen er...

  4. Ekström Catering internetmarknadsföring - Förnyande av hemsidan till ett effektivare marknadsföringsverktyg

    OpenAIRE

    Rönn, Julia

    2013-01-01

    Syftet med detta examensarbete är att visa hur effektiv en uppdaterad och genomtänkt hemsida kan vara som ett marknadsföringsverktyg för Ekström Catering. I detta examensarbete motiveras också införandet av en blogg för att ytterligare ta till vara på de möjligheter som finns inom internetmarknadsföring som kan gynna företaget. Examensarbetet är grundat på teori angående internetmarknadsföring, företagshemsidor och företagsbloggar. Även intervjuer med uppdragsgivare och artiklar om föret...

  5. Indholdsform

    DEFF Research Database (Denmark)

    Widell, Peter

    Artiklen er en kritik af den danske lingvist Louis Hjelmslevs begreb om indholdsform, sådan som det bl.a. er blevet overtaget af  den funktionelle lingvistik i Danmark (Peter Harder, Lars Heltoft m.fl.). Hjelmslevs begreb om indholdsform er tænkt som led i en sofistikeret udvidelse af Saussures...... oprindelige tegnbegreb, forstået som en solidarisk forbindelse mellem et udtryk og et meningsindhold. Med baggrund i en formalsemantisk forståelse af meningsbegrebet vises det i artiklen, hvordan Hjelmslevs begreb om indholdsform i virkeligheden kollapser og bringer Hjelmslevs tegnbegreb i nærheden af Saussures...

  6. 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.

  7. 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

  8. Faktorer relaterade till genomförande av uppföljningsintervjuer med ASI – klientprofil och organisation

    OpenAIRE

    Eriksson, Jakob; Mara, Adelin

    2014-01-01

    Addiction Severity Index (ASI) är tänkt att användas både för klientarbete på individnivå och för forskning på gruppnivå. Denna studie undersöker i vilken omfattning ASI-Uppföljning genomförs samt vilka individ- och organisationsfaktorer som påverkar användningen. Studien är kvantitativ dvs presenterar statistiska analyser. Data samlades in på två sätt. Tillgång till ASI-data gjordes möjlig genom en avidentifierad fil från databasen ASI-Net och omfattade data från elva kommuner i Jönköpings l...

  9. 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 ...

  10. Ipendo Web Portal : Utveckling av en flexibel koncernportal i Microsoft Office SharePoint Server 2007

    OpenAIRE

    Wallén, Anton

    2009-01-01

    Rapporten behandlar utvecklingen av en portal som är tänkt att användas av alla olika delar av en företagskoncern, både som intranät, extranät och extern webbplats. Denna rapport undersöker vad som är viktigt att uppfylla för att skapa en portal av detta slag där kraven på flexibilitet är stora, samtidigt som de olika företagen i koncernen ska ha utrymme att agera både som enskilda företag och som medlemmar i en koncern. Rapporten undersöker även om tekniken SharePoint kan vara lämplig att an...

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. alpha-Galactosylceramide can act as a nasal vaccine adjuvant inducing protective immune responses against viral infection and tumor.

    Science.gov (United States)

    Ko, Sung-Youl; Ko, Hyun-Jeong; Chang, Woo-Sung; Park, Se-Ho; Kweon, Mi-Na; Kang, Chang-Yuil

    2005-09-01

    alpha-Galactosylceramide (alpha-GalCer) is a ligand of invariant Valpha14+ NKT cells and is presented by CD1d molecule on APC. NKT cells produce a large amount of Th1 and Th2 cytokines in response to alpha-GalCer-presented APC. In this study, we assessed whether alpha-GalCer could act as an effective nasal vaccine adjuvant for mucosal vaccine that would be capable of inducing systemic as well as mucosal immune responses. When alpha-GalCer was administered with OVA via the intranasal route to C57BL/6 and BALB/c mice, significant OVA-specific mucosal secretory IgA, systemic IgG, and CTL responses were induced with mixed Th1 and Th2 cytokine profiles seen in both strains of mice. Interestingly, as BALB/c mice were intranasally immunized with PR8 hemagglutinin Ag isolated from influenza virus A/PR/8/34 together with alpha-GalCer, significant protection was afforded against influenza viral infection. When alpha-GalCer was coimmunized with a replication-deficient live adenovirus to BALB/c mice, it significantly induced both humoral and cellular immune responses. In addition, intranasal administration of OVA with alpha-GalCer showed complete protection against EG7 tumor challenge in C57BL/6. The adjuvant effects induced by intranasal coadministration with alpha-GalCer were blocked in CD1d-/- mice, indicating that the immune responses were exclusively mediated by CD1d molecule on APC. Most interestingly, intranasally coadministered alpha-GalCer activated naive T cells and triggered them to differentiate into functional effector T cells when CFSE-labeled OT-1 cells were adoptively transferred into syngeneic mice. Overall, our results are the first to show that alpha-GalCer can act as a nasal vaccine adjuvant inducing protective immune responses against viral infections and tumors. PMID:16116223

  16. Reevaluation of atomic bomb dose in Hiroshima and Nagasaki

    International Nuclear Information System (INIS)

    The Final Report Vol. 1 of the US-Japan Joint Reassessment of Atomic Bomb Radiation Dosimetry in Hiroshima and Nagasaki, which was carried out under the Radiation Effects Research Foundation, was released on July 8, 1987. Major contents of the Report are outlined here. The bombs dropped in Hiroshima and Nagasaki are respectively estimated to be equivalent to 22 kt and 12.5 kt of TNT. The number of leakage neutrons from the bombs was 1.07 x 1023 n/kt in Hiroshima and 1.65 x 1023 n/kt in Nagasaki while the number of leakage photons was 3.04 x 1021 γ/kt in Hiroshima and 3.79 x 1022 γ/kt in Nagasaki. The effects of the scattering at the ground surface and atmospheric humidity on the kerma in tissue in Hiroshima are shown. Investigation of the contributions of prompt and delayed neutrons and gamma rays to the kerma in tissue reveals that the dose of delayed gamma rays is increasingly greater than that of prompt gamma rays at points closer to the blast center. The soft tissue kerma values estimated from TL measurements made by various research institutes are compared to calculations. Measurements of neutron-induced radioactivity are also compared to calculations. Some model houses to be used for evaluation of the shielding performance of houses are proposed. Some applications of the Dosimetry System 1986 (DS86), a procedure for calculating the exposure dose of victims of the bombs developed in 1986 are also described. (Nogami, K.)

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Revisión crítico-comparada de las principales teorías científico sociales sobre la delincuencia femenina (Vergleichend kritische Überarbeitung der wichtigsten wissenschaftlichen und sozialen Theorien über die Fraunkriminalität

    Directory of Open Access Journals (Sweden)

    Gudrun Stenglein

    2013-03-01

    Full Text Available Wenn man von Verbrechen spricht, scheint man mit einem reinen männlichen Phänomen konfrontiert zu sein. Die wissenschaftlichen Arbeiten über Kriminalität beschäftigen sich normalerweise mit dem Verhalten männlicher Krimineller. Die Frauen werden nur als passive Subjekte, meist als Opfer dargestellt. Die Frauenkriminalitätsproblematik wird aber immer gewichtiger, die Anzahl der Delikte, die durch Frauen begangen werden, und der Frauen als Strafgefangene wächst. Aber in der akademischen Welt wird diese Problematik nach wie vor als nicht wichtig dargestellt, sie spielt eine wesentlich kleinere Rolle. Das Phänomen der Frauenkriminalität wird bis zum heutigen Tage mit dem biologischen Unterschied, mit der Form des Seins der Frau erklärt. Die Vorstellungswelt der Frau beschäftigt sich nur mit der Suche nach einem adäquaten Parter und mit der Rolle als Mutter und Ehefrau, die sich um ihre Familie kümmert. Jahrhundertelang war dieses Thema auf die Verhaltensweisen in Verbindung mit der sozialen Reputation beschränkt. Mit diesem Artikel wird eine Einleitung in die verschiedenen biologischen und sozialen Erklärungsansätze dieses Phänomens unter dem besonderen funktionalistischen Blickwinkel der Rollentheorie und der Theorie der sozialen Kontrolle gegeben. Ein anderer Ansatzpunkt ist die Etikettierungsthorie, Labeling Approach. Einige Erklärungsansätze, wie die Sozialisierung der Frau, haben nach wie vor Gültigkeit, vor allem, weil es sich bei dem Problem der Frauenkriminalität um ein multidisziplinäres Thema handelt. Die individuellen und sozialen Faktoren müssen miteinander verbunden werden. Die Gesellschaft macht aus den Personen, was sie sind, zumindest potenziert sie die individuellen Bedingungen. Einige Erklärungen wurden mit der Zeit relativiert. Manche können mitlerweile für veraltet gehalten werden, andere sind in ihren Ansichtsweisen teilweise zu beschränkt, so dass sie heutzutage als befremdlich oder

  4. A committed hemopoietic precursor to innate lymphoid cells

    Science.gov (United States)

    Constantinides, Michael G.; McDonald, Benjamin D.; Verhoef, Philip A.; Bendelac, Albert

    2014-01-01

    Innate lymphoid cells (ILC) specialize in the rapid secretion of polarized sets of cytokines and chemokines to combat infection and promote tissue repair at mucosal barriers.1–9 Their diversity and similarities with previously characterized NK cells and lymphoid tissue inducers (LTi) have prompted a provisional classification of all innate lymphocytes into groups 1, 2 and 3 based solely on cytokine properties,10 but their developmental pathways and lineage relationships remain elusive. Using lineage tracing and transfer studies, we identified and characterized a novel subset of lymphoid precursors in fetal liver and adult bone marrow that transiently expressed high amounts of PLZF, a transcription factor previously associated with NKT cell development.11,12 PLZFhigh cells were committed ILC progenitors with multiple ILC1, ILC2 and ILC3 potential at the clonal level. They excluded classical LTi and NK cells, but included a peculiar subset of NK1.1+DX5− ‘NK-like’ cells residing in the liver. Deletion of PLZF markedly altered the development of several ILC subsets, but not LTi or NK cells. PLZFhigh precursors also expressed high amounts of Id2 and GATA3, as well as TOX, a known regulator of PLZF-independent NK and LTi lineages.13 These findings establish novel lineage relationships between ILC, NK and LTi cells, and identify the common precursor to ILC, termed ILCP. They also reveal the broad, defining role of PLZF in the differentiation of innate lymphocytes. PMID:24509713

  5. 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.

  6. 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.

  7. Gabriele Winker, Nina Degele: Intersektionalität. Zur Analyse sozialer Ungleichheiten. Bielefeld: transcript Verlag 2009.

    Directory of Open Access Journals (Sweden)

    Heike Kahlert

    2010-03-01

    Full Text Available Gabriele Winker und Nina Degele legen mit ihrer kompakten Monographie erstmals für den deutschsprachigen Raum eine in Theorie, Methodologie und Empirie stringente eigenständige Abhandlung zur intersektionalen Analyse von sozialen Ungleichheiten vor. Das in jeder Hinsicht übersichtlich gestaltete Buch besticht durch eine begründete Argumentation, insbesondere in Bezug auf die theoretischen Vorentscheidungen, durch eine klare Gliederung und vor allem durch die Schritt für Schritt nachvollziehbare Umsetzung des vorgeschlagenen theoretischen und methodologischen Rahmens in die empirische Sozialforschung. Es ist daher uneingeschränkt empfehlenswert, auch für den Einsatz in der Hochschullehre, und es ist von hohem Anregungspotential für die wissenschaftliche Weiterentwicklung intersektionaler Analysen von sozialen Ungleichheiten.This compact monograph by Gabriele Winker and Nina Degele, intended for a German-speaking readership, provides a theoretically, methodologically, and empirically stringent as well as independent critique of intersectional analysis of social inequalities. The book, which is in every sense clearly organized, is striking because of its well-founded argumentation (especially in terms of the authors’ theoretical decisions, its clear structure, and most notably its step-by-step and comprehensible application of the suggested theoretical and methodological framework for empirical social research. The book is thus recommended without reserve, also for use in higher education, and it has the potential to inspire further scientific development of intersectional analysis of social inequities.

  8. 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.

  9. Lou-Salomé Heer: „Das wahre Geschlecht“. Der populärwissenschaftliche Geschlechterdiskurs im SPIEGEL (1947–2010. Zürich: Chronos Verlag 2012.

    Directory of Open Access Journals (Sweden)

    Heike Kahlert

    2013-05-01

    Full Text Available Die vorliegende Diskursanalyse des populärwissenschaftlichen Geschlechterwissens war zweifelsohne überfällig. Lou-Salomé Heer zeigt in ihrer empirischen Studie, die auf einer Lizenziatsarbeit an der Universität Zürich beruht, am Beispiel von Titelgeschichten und Titelbildern des SPIEGEL, dass der mediale Geschlechterdiskurs seit den 1990er Jahren durch die Soziobiologie geprägt wird. Die anregende explorative Untersuchung lenkt die Aufmerksamkeit auf die ambivalente Bedeutung der Medien bei der Produktion und Reproduktion (populärwissenschaftlichen Geschlechterwissens und gibt Anstöße für vertiefende Studien. In methodischer Hinsicht bleibt die vorliegende Analyse jedoch leider unbefriedigend, was den Erkenntnisgewinn einschränkt.The present discourse analytical study of popular scientific gender knowledge was without doubt overdue. In her empirical study, which is based on a Master’s thesis at the University of Zurich, Lou-Salomé Heer illustrates, using cover stories and photos of the SPIEGEL, that the medial gender discourse has been characterized by sociobiology since the 1990s. The stimulating, explorative analysis draws the attention to the ambivalent significance of media in the production and reproduction of (popular scientific gender knowledge and provides impulses for further studies. The present analysis does, however, remain unsatisfactory methodologically, which limits the possible gain in knowledge.

  10. Anomalous Kinetics of Hard Charged Particles Dynamical Renormalization Group Resummation

    CERN Document Server

    Boyanovsky, D

    1999-01-01

    We study the kinetics of the distribution function for charged particles of hard momentum in scalar QED. The goal is to understand the effects of infrared divergences associated with the exchange of quasistatic magnetic photons in the relaxation of the distribution function. We begin by obtaining a kinetic transport equation for the distribution function for hard charged scalars in a perturbative expansion that includes hard thermal loop resummation. Solving this transport equation, the infrared divergences arising from absorption and emission of soft quasi-static magnetic photons are manifest in logarithmic secular terms. We then implement the dynamical renormalization group resummation of these secular terms in the relaxation time approximation. The distribution function (in the linearized regime) is found to approach equilibrium as $\\delta n_k(t) =\\delta n_k(t_o) e^{-2\\alpha T (t-t_o) and $\\alpha =e^2/4\\pi$. This anomalous relaxation is recognized to be the square of the relaxation of the single particle p...

  11. 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....... Denne artikel gennemgår metoden og fortæller om både positive resultater og udfordringer i tre danske organisationer: Et softwarehus, en bank, og et universitet. De tre cases illustrer meget forskellige anvendelsessituationer af Scrum set i forhold til projekternes størrelse, karakter og den...... 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...

  12. 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....... Denne artikel gennemgår metoden og fortæller om både positive resultater og udfordringer i tre danske organisationer: Et softwarehus, en bank, og et universitet. De tre cases illustrer meget forskellige anvendelsessituationer af Scrum set i forhold til projekternes størrelse, karakter og den...... 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...

  13. Probiotics and immunosenescence: cheese as a carrier.

    Science.gov (United States)

    Ibrahim, Fandi; Ruvio, Suvi; Granlund, Linda; Salminen, Seppo; Viitanen, Matti; Ouwehand, Arthur C

    2010-06-01

    Oral intake of specific probiotics has been reported to enhance the immunity of the elderly. Earlier studies have used milk or yoghurt as a probiotic carrier. We chose a commercial probiotic cheese to evaluate its potential as a probiotic food. Thirty-one healthy elderly volunteers (21 female, 10 male) aged from 72 to 103 (median 86) consumed a commercial probiotic cheese containing approximately 10(9) CFU day(-1) of Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM. The 4-week probiotic intervention was preceded by a 2-week consumption of probiotic-free cheese (run-in) and followed by a 4-week wash-out period with the same control cheese. The cytotoxicity of peripheral blood mononuclear cells (PBMCs), the relative numbers of natural killer (NK) and NKT cells in the total PBMCs, and phagocytic activity were assessed. Consumption of the probiotic cheese significantly increased the cytotoxicity of NK cells. A significant increase in phagocytosis was observed for both the control and the probiotic cheese. Cheese was found to be an effective carrier for the study of probiotics, and daily consumption of the probiotic enhanced parameters of innate immunity in elderly volunteers. It remains to be determined whether this enhancement correlates with a beneficial effect on the health of the elderly population. PMID:20236323

  14. 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

  15. 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...

  16. 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.

  17. The Epstein-Barr Virus (EBV) in T Cell and NK Cell Lymphomas: Time for a Reassessment

    Science.gov (United States)

    Gru, A. A.; Haverkos, B. H.; Freud, A. G.; Hastings, J.; Nowacki, N. B.; Barrionuevo, C.; Vigil, C. E.; Rochford, R.; Natkunam, Y.; Baiocchi, R. A.

    2015-01-01

    While Epstein-Barr virus (EBV) was initially discovered and characterized as an oncogenic virus in B cell neoplasms, it also plays a complex and multifaceted role in T/NK cell lymphomas. In B cell lymphomas, EBV-encoded proteins have been shown to directly promote immortalization and proliferation through stimulation of the NF-κB pathway and increased expression of anti-apoptotic genes. In the context of mature T/NK lymphomas (MTNKL), with the possible exception on extranodal NK/T cell lymphoma (ENKTL), the virus likely plays a more diverse and nuanced role. EBV has been shown to shape the tumor microenvironment by promoting Th2-skewed T cell responses and by increasing the expression of the immune checkpoint ligand PD-L1. The type of cell infected, the amount of plasma EBV DNA, and the degree of viral lytic replication have all been proposed to have prognostic value in T/NK cell lymphomas. Latency patterns of EBV infection have been defined using EBV-infected B cell models and have not been definitively established in T/NK cell lymphomas. Identifying the expression profile of EBV lytic proteins could allow for individualized therapy with the use of antiviral medications. More work needs to be done to determine whether EBV-associated MTNKL have distinct biological and clinical features, which can be leveraged for risk stratification, disease monitoring, and therapeutic purposes. PMID:26449716

  18. 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.

  19. APPLICATION OF SIX-COLOR FLOW CYTOMETRIC ANALYSIS FOR IMMUNE PROFILE MONITORING

    Directory of Open Access Journals (Sweden)

    I. V. Kudryavtsev

    2015-03-01

    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+. 

  20. 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.

  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. 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.

  3. Thermo-Mechanical Test of Seal System in Flexible Pipe End Fittings

    DEFF Research Database (Denmark)

    Banke, Lars

    1999-01-01

    The purpose of the end fitting seal system is to provide a leak tight termination in a flexible pipe. The seal system in a NKT flexible pipe end fitting consists of a number of ring gaskets mounted on the polymeric internal pressure sheath of the pipe. When the seal is energised the gaskets...... of the seal system geometry and its tolerances necessary to maintain a tight seal. The test is carried out in a purpose built autoclave, in which the seal system can be tested while undergoing variations in pressure and temperature.The paper will present a study on the importance of the geometry of the gasket...... and the inner liner. The inner and outer diameter of the gasket are varied to see the effectiveness of the seal mechanism. The effect of varying the width of the gasket as well as the surface roughness of the components in the seal system is analysed. Finally, it is investigated how the seal system is affected...

  4. Test of Seal System for Flexible Pipe End Fitting

    DEFF Research Database (Denmark)

    Banke, Lars; Jensen, Thomas Gregers

    1999-01-01

    The purpose of the end fitting seal system is to ensure leak proof termination of flexible pipes. The seal system of an NKT end fitting normally consists of a number of ring joint gaskets mounted in a steel sleeve on the outside of the polymeric inner liner of the pipe. The seal system is activated...... by compression of the gaskets, thus using the geometry to establish a seal towards the inner liner of the pipe and the steel sleeve of the end fitting. This paper describes how the seal system of an end fitting can be tested using an autoclave. By regulating temperature and pressure, the seal system can...... be tested up to 130oC and 51.7 MPa. Pressure, temperature and the mechanical behaviours of the pipe are measured for use in further research. The set-up is used to test the efficiency of the seal system as function of parameters such as cross sectional shapes of the gaskets, tolerances between gaskets...

  5. Imaging features of nasal-type natural killer/T-cell lymphomas: frequent involvement of skin and subcutaneous tissue

    International Nuclear Information System (INIS)

    We wanted to evaluate the radiologic characteristics of nasal-type NK/T cell lymphomas. We reviewed twenty-one cases of pathologically proven nasal-type NK/T-cell lymphomas. CT scans were obtained for 21 patients, MR image were obtained for 3 patients, and both CT and MR scans were obtained for 3 patients. The imaging features regarding patterns of the masses, extension to adjacent tissue, bony changes and the degree of contrast enhancement were evaluated. All of the 21 patients had diffuse mucosal thickening and 12 patients (12/21, 57%) also had polypoid masses. Nasal cavity lesions showed extension to the adjacent tissue in 20 cases (20/21, 95%). Adjacent bone erosion or destruction was noted in 14 cases (14/21, 67%) and the bone destruction was mild. Nasal-type NK/T-cell lymphomas revealed a tendency to involve the superficial soft tissue and to extend into the adjacent structures. The typical imaging features of nasal-type NK/T-cell lymphoma were diffuse infiltrative lesion with or without polypoid masses in the nasal cavity and frequently extension to adjacent soft tissue, and especially the subcutaneous tissue

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  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. A spectrum of clinical manifestations caused by host immune responses against Epstein-Barr virus infections.

    Directory of Open Access Journals (Sweden)

    Iwatsuki K

    2004-08-01

    Full Text Available Epstein-Barr virus (EBV, or human herpesvirus 4 (HHV-4, infects the vast majority of adults worldwide, and establishes both nonproductive (latent and productive (lytic infections. Host immune responses directed against both the lytic and latent cycle-associated EBV antigens induce a diversity of clinical symptoms in patients with chronic active EBV infections who usually contain an oligoclonal pool of EBV-infected lymphocyte subsets in their blood. Episomal EBV genes in the latent infection utilize an array of evasion strategies from host immune responses: the minimized expression of EBV antigens targeted by host cytotoxic T lymphocytes (CTLs, the down-regulation of cell adhesion molecule expression, and the release of virokines to inhibit the host CTLs. The oncogenic role of latent EBV infection is not yet fully understood, but latent membrane proteins (LMPs expressed during the latency cycle have essential biological properties leading to cellular gene expression and immortalization, and EBV-encoded gene products such as viral interleukin-10 (vIL-10 and bcl-2 homologue function to survive the EBV-infected cells. The subsequent oncogenic DNA damage may lead to the development of neoplasms. EBV-associated NK/T cell lymphoproliferative disorders are prevalent in Asia, but quite rare in Western countries. The genetic immunological background, therefore, is closely linked to the development of EBV-associated neoplasms.

  16. 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.

  17. Herschel und die Zukunft der Fern-Infrarot-Astronomie

    Science.gov (United States)

    Linz, Hendrik

    2015-06-01

    Schon lange ist die beobachtende Astronomie den engen Grenzen des optisch Sichbaren entwachsen und hat fast alle Bereiche des elektromagnetischen Spektrums für sich dienstbar gemacht. Im sogenannten nahen und mittleren Infrarot (Wellenlängen zwischen 1-30 μm) sowie im Millimeter- und Radio-Regime (Wellenlängen zwischen 1 mm und 10 m) ist die Erdatmosphäre relativ gut durchlässig für elektromagnetische Signale oder hat zumindest eine Vielzahl von spektral begrenzten Transmissionsfenstern, die astronomische Beobachtungen zumindest von höheren Bergen aus möglich machen. Allerdings ist das sogenannte Ferne Infrarot (FIR, 30-300 μm Wellenlänge) von der Erde aus fast völlig unzugänglich für astronomische Beobachtungen. Selbst für die besten Beobachtungsplätze der Erde bleibt die atmosphärische Transmission durch die immense Wasserdampf- Absorption auf ein absolutes Minimum beschränkt. Jedoch erlaubt uns das FIR Zugang zu Informationen, die sehr nützlich sind für die astrophysikalische Forschung und komplementär zu anderen Wellenlängen-Bereichen.

  18. Medizinische Textilien

    Science.gov (United States)

    Houis, Stéphanie; Deichmann, Thorsten; Veit, Dieter; Gries, Thomas

    Textilien werden in Form von Naht- und Verbandmaterial schon seit sehr langer Zeit eingesetzt. Bereits die Ägypter und die amerikanischen Ureinwohner verwendeten medizinische Textilen für die Wundbehandlung [1]. Verschiedene Nahtmaterialien wie Leinen (Ägypter) oder Golddraht (Griechen) wurden schon im Altertum eingesetzt [2]. Die mittelalterliche Chirurgie verwandte Scharpie als Verbandstoff. Scharpie ist ein Produkt, das durch Zupfen und Schaben eines Leinwandgewebes entsteht und eine erhöhte Saugfähigkeit besitzt. Zur Reinigung wurde Scharpie in Rotwein getränkt, die Wunde damit ausgefüllt und mit Leinenbinden fixiert. Seit den 1950er Jahren nimmt die Anzahl der Anwendungen von textilen Strukturen im intrakorporalen Bereich, z. B. als Gefäß- oder Bandersatz, stetig zu. Die textilen Strukturen können dabei an die gewünschten Eigenschaften des Produkts angepasst werden [3], sie sind in hohem Maße drapierbar und besitzen eine hohe spezifische Oberfläche, die je nach Anforderung modifiziert und funktionalisiert werden kann [4].

  19. On the Summation of Non-leading Logarithms in QCD

    Science.gov (United States)

    Dorn, H.; Otto, H.-J.; Wieczorek, E.

    Exploiting the relations between the expansion coefficients of Green's functions and those of and functions in massless QFT, the summation up to the n-th non-leading logarithms is reduced to the solution of a system of linear differential equations, which in general differ from renormalization group equations. Applying this procedure to the gluon propagator the leading log approximation is modified near the mass shell by a constant factor only. Furthermore for the gluon propagator exponentiation in terms of the running coupling constant is argued to be restricted to leading logarithms.Translated AbstractÜber die Summation nicht-dominanter Logarithmen in der QCDUnter Ausnutzung der Relation zwischen den Entwicklungskoeffizienten der Greenschen Funktionen und denen der und -Funktionen masseloser Quantenfeldtheorien wird die Summation einschließlich der n-ten nicht-dominanten Logarithmen auf die Lösung eines Systems linearer Differentialgleichungen reduziert. Diese Gleichungen sind im allgemeinen von den Renormierungsgruppengleichungen verschieden. Das Verfahren wird auf den Gluon-Propagator angewandt und es wird gezeigt, daß in der Nähe der Massenschale das Verhalten der dominanten Approximation nur durch einen konstanten Faktor modifiziert wird. Schließlich wird nachgewiesen, daß eine Exponentiation mit einer effektiven Kopplungskonstanten auf die dominanten Logarithmen beschränkt bleibt.

  20. 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

  1. 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.

  2. 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

  3. Primary NK/T-cell lymphoma of the larynx: Report of 2 cases and review of the English-, Japanese-, and Chinese-language literature.

    Science.gov (United States)

    Zhu, Su-Yu; Yuan, Yuan; Liu, Ke; Zeng, Liang; Zhou, Ju-Mei; Lu, Qiong-Hui; Huang, Zai-Jie

    2016-01-01

    Natural killer/T (NK/T) -cell lymphoma in the larynx is extremely rare, as only 29 cases have been previously reported in the English-language, Japanese-language, and Chinese-language literature. Its characteristics have never been systematically illustrated. We report 2 new cases of laryngeal NK/T-cell lymphoma, and we discuss the process of the diagnosis of this disease, the choice of treatment, and treatment outcomes. We also summarize all 31 cases reported thus far. Symptoms of laryngeal NK/T-cell lymphoma are difficult to differentiate from those of other laryngeal diseases. The most common laryngeal subsite in the reported cases was the supraglottis, and roughly one-third of these cases involved the cervical lymph nodes. Because of our limited experience with this disease and the difficulties encountered in interpreting the pathologic findings, most patients required multiple biopsies over a few months before their diagnosis was confirmed. The outcome of treatment was generally poor. Radiotherapy, alone or combined with chemotherapy, was superior to chemotherapy alone in treating this disease in its early stages. In view of the frequency of local lymph node metastasis, irradiation fields should cover the entire cervical area. We believe that prompt diagnosis and treatment with radiotherapy are both critical to improving survival for patients with laryngeal NK/T-cell lymphoma. PMID:27140022

  4. 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.

  5. 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.

  6. LYMPHOCYTE PHENOTYPE IN PATIENTS WITH SKIN MELANOMA AFTER IMMUNOTHERAPY OF ACTIVATED LYMPHOCYTES

    Directory of Open Access Journals (Sweden)

    E. V. Abakushina

    2015-01-01

    Full Text Available The major medical problem in the treatment of skin melanoma is improvement methods of treatment, increasing their effectiveness and safety. In this study, adoptive immunotherapy, using lymphocytes activated in vitro, was performed in 15 patients with metastatic melanoma. Evaluated the phenotype of peripheral blood lymphocytes and activation markers (HLA-DR, CD25, CD314, CD38, CD69 before and 3-4 weeks after immunotherapy. It is shown that for these patients is characterized by increasing the number of CD25+ and Treg lymphocytes in the bloodstream, which has not changed after immunotherapy. Adoptive immunotherapy in combination with chemotherapy resulted in a decrease of absolute number of lymphocyte, B- and T-lymphocytes, T helper cells, NKT-cells, CD314+ lymphocytes, CD38+ lymphocytes and immature T-lymphocytes (CD3+CD38+ (р < 0,05. However, there was a positive dynamic to increase the percentage of NK-cells to 32% and CD69+NK-cells to 21% and significant increase in expression of HLA-DR on all lymphocytes (p < 0.05. Adoptive immunotherapy characterized by the absence of side effects and can be recommended as accompanying to basic radiation and chemotherapy.

  7. The Role of Lipopeptidophosphoglycan in the Immune Response to Entamoeba histolytica

    Directory of Open Access Journals (Sweden)

    Isabel Wong-Baeza

    2010-01-01

    Full Text Available The sensing of Pathogen Associated Molecular Patterns (PAMPs by innate immune receptors, such as Toll-like receptors (TLRs, is the first step in the inflammatory response to pathogens. Entamoeba histolytica, the etiological agent of amebiasis, has a surface molecule with the characteristics of a PAMP. This molecule, which was termed lipopeptidophosphoglycan (LPPG, is recognized through TLR2 and TLR4 and leads to the release of cytokines from human monocytes, macrophages, and dendritic cells; LPPG-activated dendritic cells have increased expression of costimulatory molecules. LPPG activates NKT cells in a CD1d-dependent manner, and this interaction limits amebic liver abscess development. LPPG also induces antibody production, and anti-LPPG antibodies prevent disease development in animal models of amebiasis. Because LPPG is recognized by both the innate and the adaptive immune system (it is a “Pamptigen”, it may be a good candidate to develop a vaccine against E. histolytica infection and an effective adjuvant.

  8. Test Results For a 25-m Prototype Fault Current Limiting HTS Cable for Project Hydra

    Energy Technology Data Exchange (ETDEWEB)

    Rey, Christopher M [ORNL; Duckworth, Robert C [ORNL; Demko, Jonathan A [ORNL; Ellis, Alvin R [ORNL; Gouge, Michael J [ORNL; James, David Randy [ORNL; Tuncer, Enis [ORNL

    2010-01-01

    The Oak Ridge National Laboratory (ORNL) has tested a 25-m long prototype High Temperature Superconducting (HTS) cable with inherent Fault-Current Limiting (FCL) capability at its recently upgraded HTS cable test facility in Oak Ridge, TN. The HTS-FCL cable and terminations were designed and fabricated by Ultera, which is a joint venture of Southwire and nkt cables with FCL features and HTS wire provided by American Superconductor Corporation. The overall project is sponsored by the U.S. Department of Homeland Security. The ultimate goal of the 25-m HTS-FCL cable test program was to verify the design and ensure the operational integrity for the eventual installation of a ~ 200-m fully functional HTS-FCL cable in the Consolidated Edison electric grid located in downtown New York City. The 25-m HTS-FCL cable consisted of a three-phase (3- ) Triax design with a cold dielectric between the phases. The HTS-FCL cable had an operational voltage of 13.8 kV phase-to-phase and an operating current of 4000 Arms per phase, which is the highest operating current to date of any HTS cable. The 25-m HTS-FCL cable was subjected to a series of cryogenic and electrical tests. Test results from the 25-m HTS-FCL cable are presented and discussed.

  9. 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

  10. Innate immune recognition of cancer.

    Science.gov (United States)

    Woo, Seng-Ryong; Corrales, Leticia; Gajewski, Thomas F

    2015-01-01

    The observation that a subset of cancer patients show evidence for spontaneous CD8+ T cell priming against tumor-associated antigens has generated renewed interest in the innate immune pathways that might serve as a bridge to an adaptive immune response to tumors. Manipulation of this endogenous T cell response with therapeutic intent-for example, using blocking antibodies inhibiting PD-1/PD-L1 (programmed death-1/programmed death ligand 1) interactions-is showing impressive clinical results. As such, understanding the innate immune mechanisms that enable this T cell response has important clinical relevance. Defined innate immune interactions in the cancer context include recognition by innate cell populations (NK cells, NKT cells, and γδ T cells) and also by dendritic cells and macrophages in response to damage-associated molecular patterns (DAMPs). Recent evidence has indicated that the major DAMP driving host antitumor immune responses is tumor-derived DNA, sensed by the stimulator of interferon gene (STING) pathway and driving type I IFN production. A deeper knowledge of the clinically relevant innate immune pathways involved in the recognition of tumors is leading toward new therapeutic strategies for cancer treatment. PMID:25622193

  11. 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.

  12. 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.

  13. Test Results for a 25 Meter Prototype Fault Current Limiting Hts Cable for Project Hydra

    Science.gov (United States)

    Rey, C. M.; Duckworth, R. C.; Demko, J. A.; Ellis, A.; James, D. R.; Gouge, M. J.; Tuncer, E.

    2010-04-01

    The Oak Ridge National Laboratory (ORNL) has tested a 25-m long prototype High Temperature Superconducting (HTS) cable with inherent Fault-Current Limiting (FCL) capability at its HTS cable test facility. The HTS-FCL cable and terminations were designed and fabricated by Ultera, which is a joint venture between Southwire and nkt cables. System integration and HTS wire were provided by American Superconductor Corporation who was the overall team leader of the project. The ultimate goal of the 25-m HTS-FCL cable test program was to verify the design and ensure the operational integrity for the eventual installation of a ˜200-m fully functional HTS-FCL cable in the Consolidated Edison electric grid located in downtown New York City. The 25-m HTS-FCL cable consisted of a three-phase (3-Φ) HTS Triax™ design with a cold dielectric between the phases. The HTS-FCL cable had an operational voltage of 13.8 kV phase-to-phase (7967 V phase-to-ground) and an operating current of 4000 Arms per phase, which is the highest operating current to date of any HTS cable. The 25-m HTS-FCL cable was subjected to a series of cryogenic and electrical tests. Test results from the 25-m HTS-FCL cable are presented and discussed.

  14. 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.

  15. 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.

  16. Yeast culture has anti-inflammatory effects and specifically activates NK cells.

    Science.gov (United States)

    Jensen, G S; Patterson, K M; Yoon, I

    2008-11-01

    Yeast culture is widely used in animal feed and has been linked to beneficial effects on animal health and production. This study examined the anti-oxidant and immunomodulating effects of a consumable yeast culture, XP, in vitro. An aqueous extract of XP contained anti-oxidants able to enter living cells and quench free radicals. The XP extract induced an increased expression of CD69 and CD25 on NK and NKT cells, and an increased cytotoxic response to K562 tumor cells. The XP extract amplified ProteinA-induced B cell activation in vitro, as measured by induction of the CD86 antigen on B lymphoblasts in 7-day cultures. The data show an anti-inflammatory effect of the XP extract in conjunction with activation of NK cells and B lymphocytes in vitro. Further in vivo studies are needed to examine the impact of XP in animals with bacterial and viral infections, as well as around the time of vaccination. PMID:17915321

  17. 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.

  18. „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.”

  19. 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.)

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. The novel mitochondria-targeted antioxidant SkQ1 modulates angiogenesis and inflammatory micromilieu in a murine orthotopic model of pancreatic cancer.

    Science.gov (United States)

    Bazhin, Alexandr V; Yang, Yuhui; D'Haese, Jan G; Werner, Jens; Philippov, Pavel P; Karakhanova, Svetlana

    2016-07-01

    Our understanding in the last few years about reactive oxygen species (ROS) has changed from being harmful substances to crucial intra- and extracellular messengers as well as important regulators controlling a wide spectrum of signaling pathways, including those in cancer immunology. Therefore, these multiple essential roles of ROS and especially of mitochondria-derived ROS in malignant transformation and cancer progression make them a promising target for anticancer therapy. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the world. A link between ROS, antioxidants and the PDAC development and progression has been recently established. Therefore, usage of specific highly efficient antioxidants could bring an option for treatment and/or prevention of PDAC. 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) is a new antioxidant with the highest mitochondrion membrane penetrating ability and potent antioxidant capability. In this work, we investigated an impact of SkQ1 on tumor angiogenesis, immune micromilieu, and oncological parameters in the orthotopic Panc02 murine model of PDAC. We showed that in this model SkQ1 treatment leads to the elevation of pro-angiogenic factors and to building of mainly an anti-inflammatory cytokine milieu. On the cellular level we showed an increase in a percentage of memory T cells and a decrease in frequency on natural killer T (NKT) cells. At the same time, SkQ1 was ineffective in the improvement of oncological parameters of PDAC-bearing mice. New studies are needed to clarify the absence of therapeutic and/or prophylactic benefits of the antioxidant. PMID:26914404

  6. 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.

  7. 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

  8. 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.

  9. Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.

    Directory of Open Access Journals (Sweden)

    Sine K Kratholm

    Full Text Available Interleukin (IL -21 is produced by Natural Killer T (NKT cells and CD4(+ T cells and is produced in response to virus infections, where IL-21 has been shown to be essential in adaptive immune responses. Cells from the innate immune system such as Natural Killer (NK cells and macrophages are also important in immune protection against virus. These cells express the IL-21 receptor (IL-21R and respond to IL-21 with increased cytotoxicity and cytokine production. Currently, however it is not known whether IL-21 plays a significant role in innate immune responses to virus infections. The purpose of this study was to investigate the role of IL-21 and IL-21R in the innate immune response to a virus infection. We used C57BL/6 wild type (WT and IL-21R knock out (KO mice in a murine vaginal Herpes Simplex Virus type 2 (HSV-2 infection model to show that IL-21 - IL-21R signalling is indeed important in innate immune responses against HSV-2. We found that the IL-21R was expressed in the vaginal epithelium in uninfected (u.i WT mice, and expression increased early after HSV-2 infection. IL-21R KO mice exhibited increased vaginal viral titers on day 2 and 3 post infection (p.i. and subsequently developed significantly higher disease scores and a lower survival rate compared to WT mice. In addition, WT mice infected with HSV-2 receiving intra-vaginal pre-treatment with murine recombinant IL-21 (mIL-21 had decreased vaginal viral titers on day 2 p.i., significantly lower disease scores, and a higher survival rate compared to infected untreated WT controls. Collectively our data demonstrate the novel finding that the IL-21R plays a critical role in regulating innate immune responses against HSV-2 infection.

  10. Flow Cytometric Analysis of T, B, and NK Cells Antigens in Patients with Mycosis Fungoides

    Directory of Open Access Journals (Sweden)

    Serkan Yazıcı

    2015-01-01

    Full Text Available 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.

  11. 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

  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. The multifaceted effects of polysaccharides isolated from Dendrobium huoshanense on immune functions with the induction of interleukin-1 receptor antagonist (IL-1ra in monocytes.

    Directory of Open Access Journals (Sweden)

    Juway Lin

    Full Text Available Dendrobium huoshanense is a valuable and versatile Chinese herbal medicine with the anecdotal claims of cancer prevention and anti-inflammation. However, its immunological activities are limited to in vitro studies on a few cytokines and immune cell functions. First, we investigated the effects of polysaccharides isolated from DH (DH-PS on inducing a panel of cytokines/chemokines in mice in vivo and human in vitro. We found that DH polysaccharides (DH-PS induced TH1, TH2, inflammatory cytokines and chemokines in mouse in vivo and human cells in vitro. Secondly, we demonstrated that DH-PS expanded mouse splenocytes in vivo including CD4(+ T cells, CD8(+ T cells, B cells, NK cells, NKT cells, monocytes/macrophages, granulocytes and regulatory T cells. Notably, DH-PS induced an anti-inflammatory molecule, IL-1ra, in mouse and human immune cells, especially monocytes. The serum level of IL-1ra elicited by the injection of DH-PS was over 10 folds of IL-1β, suggesting that DH-PS-induced anti-inflammatory activities might over-ride the inflammatory ones mediated by IL-1β. The signaling pathways of DH-PS-induced IL-1ra production was shown to involve ERK/ELK, p38 MAPK, PI3K and NFκB. Finally, we observed that IL-1ra level induced by DH-PS was significantly higher than that by F3, a polysaccharide extract isolated from another popular Chinese herbal medicine, Ganoderma lucidum. These results indicated that DH-PS might have potential applications for ameliorating IL-1-induced pathogenic conditions.

  14. Human tumor-derived exosomes down-modulate NKG2D expression.

    Science.gov (United States)

    Clayton, Aled; Mitchell, J Paul; Court, Jacquelyn; Linnane, Seamus; Mason, Malcolm D; Tabi, Zsuzsanna

    2008-06-01

    NKG2D is an activating receptor for NK, NKT, CD8(+), and gammadelta(+) T cells, whose aberrant loss in cancer is a key mechanism of immune evasion. Soluble NKG2D ligands and growth factors, such as TGFbeta1 emanating from tumors, are mechanisms for down-regulating NKG2D expression. Cancers thereby impair the capacity of lymphocytes to recognize and destroy them. In this study, we show that exosomes derived from cancer cells express ligands for NKG2D and express TGFbeta1, and we investigate the impact of such exosomes on CD8(+) T and NK cell NKG2D expression and on NKG2D-dependent functions. Exosomes produced by various cancer cell lines in vitro, or isolated from pleural effusions of mesothelioma patients triggered down-regulation of surface NKG2D expression by NK cells and CD8(+) T cells. This decrease was rapid, sustained, and resulted from direct interactions between exosomes and NK cells or CD8(+) T cells. Other markers (CD4, CD8, CD56, CD16, CD94, or CD69) remained unchanged, indicating the selectivity and nonactivatory nature of the response. Exosomal NKG2D ligands were partially responsible for this effect, as down-modulation of NKG2D was slightly attenuated in the presence of MICA-specific Ab. In contrast, TGFbeta1-neutralizing Ab strongly abrogated NKG2D down-modulation, suggesting exosomally expressed TGFbeta as the principal mechanism. Lymphocyte effector function was impaired by pretreatment with tumor exosomes, as these cells exhibited poor NKG2D-dependent production of IFN-gamma and poor NKG2D-dependent killing function. This hyporesponsiveness was evident even in the presence of IL-15, a strong inducer of NKG2D. Our data show that NKG2D is a likely physiological target for exosome-mediated immune evasion in cancer. PMID:18490724

  15. ESWL aus der Sicht des Osteologen

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.)

  17. Measurement of Thermal Dependencies of PBG Fiber Properties

    Energy Technology Data Exchange (ETDEWEB)

    Laouar, Rachik

    2011-07-06

    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 ({gamma}{sub SiO{sub 2}} = 1.19 x 10{sup -6} 1/K, {gamma}{sub air} = -9 x 10{sup -7} 1/K with {gamma} = 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 (k{sub z}) 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 (TE{sub 00}), and the experimental demonstration of TM-like mode propagation in the HC-633

  18. The role of intrahepatic CD3 +/CD4 −/CD8 − double negative T (DN T) cells in enhanced acetaminophen toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Getachew, Yonas, E-mail: yonas.getachew@utsouthwestern.edu [Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9151 (United States); Cusimano, Frank A. [Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9151 (United States); James, Laura P. [Department of Pediatrics, University of Arkansas, Little Rock, AR (United States); Thiele, Dwain L. [Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9151 (United States)

    2014-10-15

    The role of the immune system, specifically NK, NKT and CD3 cells, in acetaminophen (APAP) induced liver injury remains inconsistently defined. In the present study, wild type (C57BL/6J) mice and granzyme B deficient (GrB −/−) mice were treated with acetaminophen to assess the role of the immune system in acute liver injury. Doses of acetaminophen that induced sub lethal liver injury in wild type mice unexpectedly produced fatal hepatotoxicity in granzyme B deficient (GrB −/−) mice. Analysis revealed that GrB −/− mice had an increased population of intrahepatic CD3 (+), CD4 (−), and CD8 (−) lymphocytes expressing the CD69 activation marker and Fas ligand. Depletion of these cells in the GrB −/− and wild type mice made them less susceptible to APAP injury, while depletion of NK1.1 (+) cells or both CD4 (+) and CD8 (+) T cells failed to provide the same hepatoprotection. Transfer of the GrB −/− IHLs further exacerbated liver injury and increased mortality in wild type mice but not in LRP/LPR mice, lacking fas expression. Conclusions: Acetaminophen toxicity is enhanced by the presence of activated, FasL expressing intrahepatic CD3 (+), CD4 (−), CD8 (−), NK1.1 (−) T cells. Depletion of these cells from GrB −/− mice and wild type mice greatly reduces mortality and improves the course of liver injury recovery. - Highlights: • Intrahepatic lymphocytes (IHLs) from GrB −/− mice harbor activated DNT cells. • IHLs from GrB −/− mice exhibit enhanced Fas ligand expression. • Acetaminophen toxicity is enhanced by activated, FasL expressing DNT cells.

  19. Co-Expansion of Cytokine-Induced Killer Cells and Vγ9Vδ2 T Cells for CAR T-Cell Therapy.

    Science.gov (United States)

    Du, Shou-Hui; Li, Zhendong; Chen, Can; Tan, Wee-Kiat; Chi, Zhixia; Kwang, Timothy Weixin; Xu, Xue-Hu; Wang, Shu

    2016-01-01

    Gamma delta (γδ) T cells and cytokine-induced killer (CIK) cells, which are a heterogeneous population of T lymphocytes and natural killer T (NKT) cells, have been separately expanded ex vivo and shown to be capable of targeting and mediating cytotoxicity against various tumor cells in a major histocompatibility complex-unrestricted manner. However, the co-expansion and co-administration of these immune cells have not been explored. In this study we describe an efficient method to expand simultaneously both CIK and Vγ9Vδ2 T cells, termed as CIKZ cells, from human peripheral blood mononuclear cells (PBMCs) using Zometa, interferon-gamma (IFN-γ), interleukin 2 (IL-2), anti-CD3 antibody and engineered K562 feeder cells expressing CD64, CD137L and CD86. A 21-day culture of PBMCs with this method yielded nearly 20,000-fold expansion of CIKZ cells with γδ T cells making up over 20% of the expanded population. The expanded CIKZ cells exhibited antitumor cytotoxicity and could be modified to express anti-CD19 chimeric antigen receptor (CAR), anti-CEA CAR, and anti-HER2 CAR to enhance their specificity and cytotoxicity against CD19-, CEA-, or HER2-positive tumor cells. The tumor inhibitory activity of anti-CD19 CAR-modified CIKZ cells was further demonstrated in vivo in a Raji tumor mouse model. The findings herein substantiate the feasibility of co-expanding CIK and γδ cells for adoptive cellular immunotherapy applications such as CAR T-cell therapy against cancer. PMID:27598655

  20. IL-21 and chronic hepatitis B virus infection%IL-21与慢性乙型病毒性肝炎的关系研究

    Institute of Scientific and Technical Information of China (English)

    胡春蓉; 石统东

    2011-01-01

    白细胞介素21是一类具有潜在的免疫调节作用、含有4个α螺旋结构的Ⅰ型细胞因子,要由CD4+T和NKT细胞分泌产生.其受体分布极其广泛,过与IL-21R结合后,L-21参与子机体的多重免疫调节.如:促进Tfh、Th17等淋巴细胞增殖,强CD8+T和NK细胞的细胞毒性,导B分化为浆细胞;同时又可抑制DC细胞的效应,进B细胞和NK细胞调亡,及负性调节Teg细胞的免疫抑制作用.免疫耐受是HBV病毒持续感染的根本原因,IL-21在慢性乙肝病毒感染的清除及病毒抗原的血清学转换中可能发挥一定的调控作用.%Interleukin-21(IL-21), a potent immunomodulatory four-alpha-helical-bundle type I cytokine, is produced by NKT and CD4+ T cells. The receptor of IL-21 is comprehensive. The interaction of IL-21 with its receptor plays an important role in both innate and adaptive immune responses. These actions include positive effects such as enhanced proliferation of lymphoid cells, increased cytotoxicity of CD8+T cells and natural killer (NK) cells, and differentiation of B cells into plasma cells. Therefore, it is important to study the function of IL-21 in eliminating HBV and HBeAg/HBeAb seroconversion for patients with chronic hepatitis B.

  1. Cooperation between Monocyte-Derived Cells and Lymphoid Cells in the Acute Response to a Bacterial Lung Pathogen.

    Directory of Open Access Journals (Sweden)

    Andrew S Brown

    2016-06-01

    Full Text Available Legionella pneumophila is the causative agent of Legionnaires' disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication of L. pneumophila, however the contributions of other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods to characterise the major inflammatory cells in lung after acute respiratory infection of mice with L. pneumophila. We observed that the numbers of alveolar macrophages rapidly decreased after infection coincident with a rapid infiltration of the lung by monocyte-derived cells (MC, which, together with neutrophils, became the dominant inflammatory cells associated with the bacteria. Using mice in which the ability of MC to infiltrate tissues is impaired it was found that MC were required for bacterial clearance and were the major source of IL12. IL12 was needed to induce IFNγ production by lymphoid cells including NK cells, memory T cells, NKT cells and γδ T cells. Memory T cells that produced IFNγ appeared to be circulating effector/memory T cells that infiltrated the lung after infection. IFNγ production by memory T cells was stimulated in an antigen-independent fashion and could effectively clear bacteria from the lung indicating that memory T cells are an important contributor to innate bacterial defence. We also determined that a major function of IFNγ was to stimulate bactericidal activity of MC. On the other hand, neutrophils did not require IFNγ to kill bacteria and alveolar macrophages remained poorly bactericidal even in the presence of IFNγ. This work has revealed a cooperative innate immune circuit between lymphoid cells and MC that combats acute L. pneumophila infection and defines a specific role for IFNγ in anti-bacterial immunity.

  2. Endoplasmic reticulum aminopeptidase-1 functions regulate key aspects of the innate immune response.

    Directory of Open Access Journals (Sweden)

    Yasser A Aldhamen

    Full Text Available Endoplasmic reticulum aminopeptidase-1 (ERAP1 is a multifunctional, ubiquitously expressed enzyme whose peptide-trimming role during antigen processing for presentation by MHC I molecules is well established, however, a role for ERAP1 in modulating global innate immune responses has not been described to date. Here we demonstrate that, relative to wild type mice, mice lacking ERAP1 exhibit exaggerated innate immune responses early during pathogen recognition, as characterized by increased activation of splenic and hepatic NK and NKT cells and enhanced production of pro-inflammatory cytokines such as IL12 and MCP1. Our data also revealed that ERAP1 is playing a critical role in NK cell development and function. We observed higher frequencies of terminally matured NK cells, as well as higher frequencies of licensed NK cells (expressing the Ly49C and Ly49I receptors in ERAP1-KO mice, results that positively correlated with an enhanced NK activation and IFNγ production by ERAP1-KO mice challenged with pro-inflammatory stimuli. Furthermore, during pathogen recognition, ERAP1 regulates IL12 production by CD11c(+ DCs specifically, with increases in IL12 production positively correlated with an increased phagocytic activity of splenic DCs and macrophages. Collectively, our results demonstrate a previously unrecognized, more central role for the ERAP1 protein in modulating several aspects of both the development of the innate immune system, and its responses during the initial stages of pathogen recognition. Such a role may explain why ERAP1 has been implicated by GWAS in the pathogenesis of autoimmune diseases that may be precipitated by aberrant responses to pathogen encounters.

  3. Endoplasmic reticulum aminopeptidase-1 functions regulate key aspects of the innate immune response.

    Science.gov (United States)

    Aldhamen, Yasser A; Seregin, Sergey S; Rastall, David P W; Aylsworth, Charles F; Pepelyayeva, Yuliya; Busuito, Christopher J; Godbehere-Roosa, Sarah; Kim, Sungjin; Amalfitano, Andrea

    2013-01-01

    Endoplasmic reticulum aminopeptidase-1 (ERAP1) is a multifunctional, ubiquitously expressed enzyme whose peptide-trimming role during antigen processing for presentation by MHC I molecules is well established, however, a role for ERAP1 in modulating global innate immune responses has not been described to date. Here we demonstrate that, relative to wild type mice, mice lacking ERAP1 exhibit exaggerated innate immune responses early during pathogen recognition, as characterized by increased activation of splenic and hepatic NK and NKT cells and enhanced production of pro-inflammatory cytokines such as IL12 and MCP1. Our data also revealed that ERAP1 is playing a critical role in NK cell development and function. We observed higher frequencies of terminally matured NK cells, as well as higher frequencies of licensed NK cells (expressing the Ly49C and Ly49I receptors) in ERAP1-KO mice, results that positively correlated with an enhanced NK activation and IFNγ production by ERAP1-KO mice challenged with pro-inflammatory stimuli. Furthermore, during pathogen recognition, ERAP1 regulates IL12 production by CD11c(+) DCs specifically, with increases in IL12 production positively correlated with an increased phagocytic activity of splenic DCs and macrophages. Collectively, our results demonstrate a previously unrecognized, more central role for the ERAP1 protein in modulating several aspects of both the development of the innate immune system, and its responses during the initial stages of pathogen recognition. Such a role may explain why ERAP1 has been implicated by GWAS in the pathogenesis of autoimmune diseases that may be precipitated by aberrant responses to pathogen encounters. PMID:23894499

  4. Report of AIDS-related lymphoma in South Korea

    International Nuclear Information System (INIS)

    The prevalence of acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL) is increasing in South Korea. The aim of this study is to identify the clinical features of ARL in South Korea. From 1998 through 2006, we retrospectively analysed a total of 23 cases of ARL from seven institutions. The patients consisted of 20 males and 3 females at a median age of 40 (range, 20-72) on diagnosis of AIDS. ARL developed at their median age of 41 (range, 24-72). The histological diagnosis was aggressive B cell lymphoma in the majority, but rare T cell and NK/T cell lymphoma were also included. Ten of 23 (43.5%) was receiving highly active anti-retroviral therapy (HAART) before the diagnosis of ARL. Fifteen of twenty-three patients were given combination chemotherapy with/without radiation, four were given radiation alone, and four did not receive any treatment against medical advice. Of 20 patients followed-up, nine were alive in remission, two alive in disease, one died of treatment related complication, four died of progressive lymphoma, four died of AIDS related causes. The response to treatment included complete response (CR) in eight (44.4%), partial response (PR) in four (22.2%) and progressive disease (PD) in three (16.7%). The response to HARRT was evaluable in 13 patients based on CD4+ cell count and human immnodeficiency virus (HIV) viral load, among which nine (69.2%) responded. Estimated median survival time was 43.9 months. Although the population of patients is small, this is the first clinical data analyses of Korean ARL patients. As a substantial portion of the patients remains alive disease free, the impact of HAART on the clinical course of ARL needs further follow-up and evaluation. (author)

  5. A subset of AID-dependent B-1a cells initiates hypersensitivity and pneumococcal pneumonia resistance.

    Science.gov (United States)

    Askenase, Phillip W; Bryniarski, Krzysztof; Paliwal, Vipin; Redegeld, Frank; Groot Kormelink, Thomas; Kerfoot, Steven; Hutchinson, Andrew T; van Loveren, Henk; Campos, Regis; Itakura, Atsuko; Majewska-Szczepanik, Monika; Yamamoto, Natsuo; Nazimek, Katarzyn; Szczepanik, Marian; Ptak, Wold

    2015-12-01

    We propose that there is a special B-1a B cell subset ("sB-1a" cells) that mediates linked processes very early after immunization to initiate cutaneous contact sensitivity (CS), delayed-type hypersensitivity (DTH), and immune resistance to pneumococcal pneumonia. Our published data indicate that in CS and DTH, these initiating processes are required for elicitation of the delayed onset and late-occurring classical T cell-mediated responses. sB-1a cells resemble memory B2 cells, as they are stimulated within 1 h of immunization and depend on T helper cytokines-uniquely IL-4 from hepatic iNKT cells--for activation and rapid migration from the peritoneal cavity to the spleen to secrete IgM antibody (Ab) and Ab-derived free light chains (FLCs) by only 1 day after immunization. Unlike conventional B-1a (cB-1a) cell-produced IgM natural Ab, IgM Ab produced by sB-1a cells has high Ag affinity owing to immunoglobulin V-region mutations induced by activation-induced cytidine deaminase (AID). The dominant cB-1a cells are increased in immunized AID-deficient mice but do not mediate initiation, CS, or pneumonia resistance because natural Ab has relatively low Ag affinity because of unmutated germ-line V regions. In CS and DTH, sB-1a IgM Ag affinity is sufficiently high to mediate complement activation for generation of C5a that, together with vasoactive mediators such as TNF-α released by FLC-sensitized mast cells, activate local endothelium for extravascular recruitment of effector T cells. We conclude by discussing the possibility of functional sB-1 cells in humans. PMID:26662721

  6. Sporadische Ataxieerkrankungen des Erwachsenen

    Directory of Open Access Journals (Sweden)

    Bürk K

    2015-01-01

    Full Text Available Krankheitsprozesse in Kleinhirn und/oder Rückenmark können zu einer chronisch progredienten Ataxie führen, die damit von vaskulären und raumfordernden Prozessen abzugrenzen ist. Neben den selteneren hereditären Formen finden sich sporadische Ataxieerkrankungen. Die sorgfältige Anamnese erlaubt häufig bereits die Diagnose einer physikalisch oder toxisch bedingten Ataxie. Weiterführende Labordiagnostik dient der Feststellung eines Vitaminmangels (Vitamin B1, B12 und E. Die Untersuchung des Liquors sollte immer erfolgen und dient dem Ausschluss eines entzündlichen Geschehens. Bei raschem Verlauf muss an die Möglichkeit einer paraneoplastischen Genese gedacht und eine ausführliche Tumorsuche angeschlossen werden. Zudem können verschiedene Infektionskrankheiten eine Ataxie auslösen (HIV, Neuroborreliose, Lues, neurotrope Viren. Nach Ausschluss einer hereditären und symptomatischen Ätiologie wird das Krankheitsbild bislang mangels weiterführender diagnostischer Optionen als idiopathische zerebelläre Ataxie („idiopathic late-onset cerebellar ataxia“ [ILOCA] bezeichnet. Die ILOCA kann im Verlauf in eine Multisystematrophie vom zerebellären Typ (MSA-C übergehen, die sich durch eine wesentlich günstigere Prognose als ihre striatonigrale Verlaufsform (MSA-P auszeichnet. Nur für einige wenige Ataxieerkrankungen existieren ursächliche oder symptomatische Therapieansätze; die Behandlung beschränkt sich daher in den meisten Fällen auf logopädische, physio- und ergotherapeutische Maßnahmen.

  7. Clinical values of multiple Epstein-Barr virus (EBV serological biomarkers detected by xMAP technology

    Directory of Open Access Journals (Sweden)

    Chen Li-Zhen

    2009-08-01

    Full Text Available Abstract Background Serological examination of Epstein-Barr virus (EBV antibodies has been performed for screening nasopharyngeal carcinoma (NPC and other EBV-associated diseases. Methods By using xMAP technology, we examined immunoglobulin (Ig A antibodies against Epstein-Barr virus (EBV VCA-gp125, p18 and IgA/IgG against EA-D, EBNA1 and gp78 in populations with distinct diseases, or with different genetic or geographic background. Sera from Cantonese NPC patients (n = 547 and healthy controls (n = 542, 90 members of high-risk NPC families and 52 non-endemic healthy individuals were tested. Thirty-five of NPC patients were recruited to observe the kinetics of EBV antibody levels during and after treatment. Patients with other EBV-associated diseases were collected, including 16 with infectious mononucleosis, 28 with nasal NK/T cell lymphoma and 14 with Hodgkin's disease. Results Both the sensitivity and specificity of each marker for NPC diagnosis ranged 61–84%, but if combined, they could reach to 84.5% and 92.4%, respectively. Almost half of NPC patients displayed decreased EBV immunoactivities shortly after therapy and tumor recurrence was accompanied with high EBV antibody reactivates. Neither the unaffected members from high-risk NPC families nor non-endemic healthy population showed statistically different EBV antibody levels compared with endemic controls. Moreover, elevated levels of specific antibodies were observed in other EBV-associated diseases, but all were lower than those in NPC. Conclusion Combined EBV serological biomarkers could improve the diagnostic values for NPC. Diverse EBV serological spectrums presented in populations with different EBV-associated diseases, but NPC patients have the highest EBV activity.

  8. Normal mouse kidneys contain activated and CD3+CD4−CD8− double-negative T lymphocytes with a distinct TCR repertoire

    Science.gov (United States)

    Ascon, Dolores B.; Ascon, Miguel; Satpute, Shailesh; Lopez-Briones, Sergio; Racusen, Lorraine; Colvin, Robert B.; Soloski, Mark J.; Rabb, Hamid

    2008-01-01

    Healthy liver, intestine, lung, and skin harbor resident lymphocytes with conventional and unconventional phenotypes. Lymphocytes also have been detected in healthy mice kidneys; however, these cells have not been well studied and have been largely overlooked. To better characterize the intra-renal lymphocytes, we extensively perfused C57BL/6J mice with PBS and then isolated mononuclear cells for flow cytometry analysis. We observed T cells, B cells, and NK cells in normal mice kidneys after extensive perfusion. Approximately 50% of kidney T lymphocytes expressed intermediate levels of CD3 (CD3int T cells). Similar to liver and lung, a high percentage of unconventional CD3+CD4−CD8− double-negative T cells was observed in normal mice kidneys, from which 11% expressed B220 antigen. Unlike the spleen and blood, the classic CD4+ and CD8+ T lymphocytes in the kidney had a high proportion of activated CD69+ and effector/memory CD44CD62L ligand phenotypes. Also, a small percentage of CD4+CD25+forkhead box p3+ and NKT cells was observed in perfused and exanguinated kidneys. In addition, a distinct TCR repertoire was found on intra-renal conventional and unconventional T cells compared with those from the spleen. Finally, after 24 h of renal ischemia reperfusion injury (IRI), increased production of cytokines IFN-γ and TNF-α by CD4+ and CD8+ T cells, isolated from perfused kidneys, was observed. These data suggest that some of these cells harbored in the kidney could be implicated in the immune response of the IRI pathogenic process. PMID:18765477

  9. Cytotoxic mediators in paradoxical HIV-tuberculosis immune reconstitution inflammatory syndrome.

    Science.gov (United States)

    Wilkinson, Katalin A; Walker, Naomi F; Meintjes, Graeme; Deffur, Armin; Nicol, Mark P; Skolimowska, Keira H; Matthews, Kerryn; Tadokera, Rebecca; Seldon, Ronnett; Maartens, Gary; Rangaka, Molebogeng X; Besra, Gurdyal S; Wilkinson, Robert J

    2015-02-15

    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) frequently complicates combined antiretroviral therapy and antituberculosis therapy in HIV-1-coinfected tuberculosis patients. The immunopathological mechanisms underlying TB-IRIS are incompletely defined, and improved understanding is required to derive new treatments and to reduce associated morbidity and mortality. We performed longitudinal and cross-sectional analyses of human PBMCs from paradoxical TB-IRIS patients and non-IRIS controls (HIV-TB-coinfected patients commencing antiretroviral therapy who did not develop TB-IRIS). Freshly isolated PBMC stimulated with heat-killed Mycobacterium tuberculosis H37Rv (hkH37Rv) were used for IFN-γ ELISPOT and RNA extraction. Stored RNA was used for microarray and RT-PCR, whereas corresponding stored culture supernatants were used for ELISA. Stored PBMC were used for perforin and granzyme B ELISPOT and flow cytometry. There were significantly increased IFN-γ responses to hkH37Rv in TB-IRIS, compared with non-IRIS PBMC (p = 0.035). Microarray analysis of hkH37Rv-stimulated PBMC indicated that perforin 1 was the most significantly upregulated gene, with granzyme B among the top five (log2 fold difference 3.587 and 2.828, respectively), in TB-IRIS. Downstream experiments using RT-PCR, ELISA, and ELISPOT confirmed the increased expression and secretion of perforin and granzyme B. Moreover, granzyme B secretion reduced in PBMC from TB-IRIS patients during corticosteroid treatment. Invariant NKT cell (CD3(+)Vα24(+)) proportions were higher in TB-IRIS patients (p = 0.004) and were a source of perforin. Our data implicate the granule exocytosis pathway in TB-IRIS pathophysiology. Further understanding of the immunopathogenesis of this condition will facilitate development of specific diagnostic and improved therapeutic options. PMID:25589068

  10. Measurement of feline cytokines interleukin-12 and interferon- g produced by heat inducible gene therapy adenoviral vector using real time PCR

    International Nuclear Information System (INIS)

    Biologic tumor therapy using Interleukin-12 (IL-12) has shown promise as an adjuvant to radiation therapy. The goals for cancer gene immunotherapy include effective eradication of established tumors and generation of a lasting systemic immune response. Among the cytokines, IL-12 has been found to be most effective gene in eradicating experimental tumors, preventing the development of metastases, and eliciting long-term antitumor immunity. Depending on the tumor model, IL-12 can exert antitumor activities via T cells, NK cells or NKT cells. It induces the production of IFN-g and IFN-inducible protein-10. It is also postulated to have antiangiogenic effects, thus inhibiting tumor formation and metastases. However, its use in clinical trials has been restricted largely owing to its systemic hematologic and hepatotoxicity. We tested the efficacy of adenovirus mediated expression of feline IL-12 gene placed under the control of an inducible promoter, the heat shock proteins (hsp70B). This places gene expression under the control of an external physical agent (hyperthermia), thus offering an 'on-off' switch and potentially reducing systemic toxicity by restricting its expression locally to the tumor. Crandell Feline Kidney (CrFK) cells were infected using the construct and the supernatant was then used to stimulate production of interferon g (IFN-g) in feline peripheral blood mononuclear cells (PBMC). As there is no commercially available ELISA kit currently available to detect or measure feline cytokines, we used real time-PCR to measure cytokine mRNA. These results will be used to initiate a clinical trial in cats with soft tissue sarcomas examining hyperthermia Induced gene therapy in conjunction with radiation therapy. The real time- PCR techniques developed here will be used to quantitatively measure cytokine mRNA levels in the punch biopsy samples obtained from the cats during the clinical trial. Support for this study was in part by NCI grant CA72745

  11. Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection

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    Vidlak Debbie

    2012-06-01

    Full Text Available Abstract Although IL-17A (commonly referred to as IL-17 has been implicated in the pathogenesis of central nervous system (CNS autoimmune disease, its role during CNS bacterial infections remains unclear. To evaluate the broader impact of IL-17 family members in the context of CNS infection, we utilized IL-17 receptor (IL-17R knockout (KO mice that lack the ability to respond to IL-17, IL-17F and IL-17E (IL-25. In this article, we demonstrate that IL-17R signaling regulates bacterial clearance as well as natural killer T (NKT cell and gamma-delta (γδ T cell infiltrates during Staphylococcus aureus-induced brain abscess formation. Specifically, when compared with wild-type (WT animals, IL-17R KO mice exhibited elevated bacterial burdens at days 7 and 14 following S. aureus infection. Additionally, IL-17R KO animals displayed elevated neutrophil chemokine production, revealing the ability to compensate for the lack of IL-17R activity. Despite these differences, innate immune cell recruitment into brain abscesses was similar in IL-17R KO and WT mice, whereas IL-17R signaling exerted a greater influence on adaptive immune cell recruitment. In particular, γδ T cell influx was increased in IL-17R KO mice at day 7 post-infection. In addition, NK1.1high infiltrates were absent in brain abscesses of IL-17R KO animals and, surprisingly, were rarely detected in the livers of uninfected IL-17R KO mice. Although IL-17 is a key regulator of neutrophils in other infection models, our data implicate an important role for IL-17R signaling in regulating adaptive immunity during CNS bacterial infection.

  12. Immune Reconstitution Kinetics following Intentionally Induced Mixed Chimerism by Nonmyeloablative Transplantation.

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    Nayoun Kim

    Full Text Available Establishing mixed chimerism is a promising approach for inducing donor-specific transplant tolerance. The establishment and maintenance of mixed chimerism may enable long-term engraftment of organ transplants while minimizing the use of immunosuppressants. Several protocols for inducing mixed chimerism have been reported; however, the exact mechanism underlying the development of immune tolerance remains to be elucidated. Therefore, understanding the kinetics of engraftment during early post-transplant period may provide insight into establishing long-term mixed chimerism and permanent transplant tolerance. In this study, we intentionally induced allogeneic mixed chimerism using a nonmyeloablative regimen by host natural killer (NK cell depletion and T cell-depleted bone marrow (BM grafts in a major histocompatibility complex (MHC-mismatched murine model and analyzed the kinetics of donor (C57BL/6 and recipient (BALB/c engraftment in the weeks following transplantation. Donor BM cells were well engrafted and stabilized without graft-versus-host disease (GVHD as early as one week post-bone marrow transplantation (BMT. Donor-derived thymic T cells were reconstituted four weeks after BMT; however, the emergence of newly developed T cells was more obvious at the periphery as early as two weeks after BMT. Also, the emergence and changes in ratio of recipient- and donor-derived NKT cells and antigen presenting cells (APCs including dendritic cells (DCs and B cells were noted after BMT. Here, we report a longitudinal analysis of the development of donor- and recipient-originated hematopoietic cells in various lymphatic tissues of intentionally induced mixed chimerism mouse model during early post-transplant period. Through the understanding of immune reconstitution at early time points after nonmyeloablative BMT, we suggest guidelines on intentionally inducing durable mixed chimerism.

  13. Systemic Toll-like receptor stimulation suppresses experimental allergic asthma and autoimmune diabetes in NOD mice.

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    Aude Aumeunier

    Full Text Available BACKGROUND: Infections may be associated with exacerbation of allergic and autoimmune diseases. Paradoxically, epidemiological and experimental data have shown that some microorganisms can also prevent these pathologies. This observation is at the origin of the hygiene hypothesis according to which the decline of infections in western countries is at the origin of the increased incidence of both Th1-mediated autoimmune diseases and Th2-mediated allergic diseases over the last decades. We have tested whether Toll-like receptor (TLR stimulation can recapitulate the protective effect of infectious agents on allergy and autoimmunity. METHODS AND FINDINGS: Here, we performed a systematic study of the disease-modifying effects of a set of natural or synthetic TLR agonists using two experimental models, ovalbumin (OVA-induced asthma and spontaneous autoimmune diabetes, presenting the same genetic background of the non obese diabetic mouse (NOD that is highly susceptible to both pathologies. In the same models, we also investigated the effect of probiotics. Additionally, we examined the effect of the genetic invalidation of MyD88 on the development of allergic asthma and spontaneous diabetes. We demonstrate that multiple TLR agonists prevent from both allergy and autoimmunity when administered parenterally. Probiotics which stimulate TLRs also protect from these two diseases. The physiological relevance of these findings is further suggested by the major acceleration of OVA-induced asthma in MyD88 invalidated mice. Our results strongly indicate that the TLR-mediated effects involve immunoregulatory cytokines such as interleukin (IL-10 and transforming growth factor (TGF-beta and different subsets of regulatory T cells, notably CD4+CD25+FoxP3+ T cells for TLR4 agonists and NKT cells for TLR3 agonists. CONCLUSIONS/SIGNIFICANCE: These observations demonstrate that systemic administration of TLR ligands can suppress both allergic and autoimmune responses

  14. Das gastral differenzierte Adenom (pyloric gland adenoma. Fact or Fiction?

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    Vieth M

    2005-01-01

    Full Text Available Das gastral differenzierte Adenom des Magens wird in der englischen Literatur als "pyloric gland adenoma" bezeichnet. Der erste Bericht zu dieser Entität erschien 1976 als Buchbeitrag, allerdings wurde die Läsion damals als eine Adenom-artige Hyperplasie mukoider Drüsen beschrieben. Erst ab 1990 wurden Pylorusdrüsen-Adenome korrekt als gastral differenzierte Adenome identifiziert und diagnostische Kriterien entwickelt. Die Bezeichnung Pylorusdrüsen-Adenom spiegelt die Entstehung aus den tiefen gastralen Drüsenverbänden wieder. Sicher sind die Pylorusdrüsen-Adenome bereits im Routine-HE-Präparat zu diagnostizieren und durch die Immunhistochemie zu bestätigen. Typischerweise exprimieren die Pylorusdrüsen-Adenome Mucin 6, das sonst nur im tiefen Drüsenkörper gefunden werden kann, über die gesamte Breite der Läsion, oft bis zur Oberfläche. Das oberflächliche Mucin 5AC ist oft nur auf eine schmale oberflächliche Zone beschränkt; die Expression kann jedoch stark variieren. Eine Kombination mit Anteilen gewöhnlicher tubulärer Adenome (intestinale Differenzierung kann beobachtet werden. Überproportional häufig ist die Magen-Corpusschleimhaut älterer Patientinnen mit Autoimmungastritis betroffen. Die Häufigkeit von Pylorusdrüsen-Adenomen wird mit 2,7 % aller Magenpolypen angegeben und ist damit nicht so selten wie vermutet. Die wenigen vorhandenen Publikationen zu diesem Thema deuten darauf hin, daß diese Entität meist fehlinterpretiert wird. Pylorusdrüsen-Adenome können im gesamten Gastrointestinaltrakt entstehen. Die klinische Bedeutung liegt in der hohen Rate (30 % der malignen Entartung. Allerdings handelt es sich hierbei vorwiegend um hochdifferenzierte Frühkarzinome mit entsprechend guter Prognose nach endoskopischer Abtragung.

  15. 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.

  16. Age and CD161 expression contribute to inter-individual variation in interleukin-23 response in CD8+ memory human T cells.

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    Hui Shen

    Full Text Available 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 (Pearson's correlation coefficient, r = -0.37, p = 0.001 source of variability observed in CD8+CD45RO+ memory T cells, with IL-23 responsiveness gradually decreasing with increasing age. Relative to cells from individuals demonstrating low responsiveness to IL-23 stimulation, CD8+CD45RO+ memory T cells from individuals demonstrating high responsiveness to IL-23 stimulation showed increased gene expression for IL-23 receptor (IL-23R, RORC (RORγt and CD161 (KLRB1, whereas RORA (RORα and STAT3 expression were equivalent. Similar to CD4+ memory T cells, IL-23 responsiveness is confined to the CD161+ subset in CD8+CD45RO+ memory T cells, suggesting a similar CD161+ precursor as has been reported for CD4+ Th17 cells. We observed a very strong positive correlation between IL-23 responsiveness and the fraction of CD161+, CD8+CD45RO+ memory T cells (r = 0.80, p<0.001. Moreover, the fraction of CD161+, CD8+CD45RO+ memory T cells gradually decreases with aging (r = -0.34, p = 0.05. Our data define the inter-individual differences in IL-23 responsiveness in peripheral blood lymphocytes from the general population. Variable expression of CD161, IL-23R and RORC affects IL-23 responsiveness and contributes to the inter-individual susceptibility to IL-23-mediated defenses and inflammatory processes.

  17. Mechanisms of enhanced osteoclastogenesis in girls and young women with Turner's Syndrome.

    Science.gov (United States)

    Faienza, Maria Felicia; Brunetti, Giacomina; Ventura, Annamaria; Piacente, Laura; Messina, Maria Francesca; De Luca, Filippo; Ciccarelli, Maria; Oranger, Angela; Mori, Giorgio; Natale, Maria Pia; Gigante, Margherita; Ranieri, Elena; Gesualdo, Loreto; Colucci, Silvia; Cavallo, Luciano; Grano, Maria

    2015-12-01

    Subjects with hypergonadotropic hypogonadism due to Turner's syndrome show low cortical mineral density, osteoporosis and risk of fractures. It is not clear if this bone fragility derives from chromosomal abnormalities or is the result of inadequate bone formation due to estrogen deficiency. The aim of this study was to investigate the cellular mechanisms underlying bone fragility in subjects with Turner's syndrome before induction of puberty and after hormonal replacement therapy (HRT). For this purpose, we have evaluated the osteoclastogenic potential of non-fractioned and T-cell depleted cultures of peripheral blood mononuclear cells (PBMCs) belonging to girls with Turner's syndrome who had not been treated with HRT yet, girls and young women who were on HRT and age-matched controls. Untreated subjects showed high FSH serum levels, whereas the other subjects displayed normal FSH serum levels. T-cell immunophenotype was analyzed through flow cytometry. Biochemical and DXA analyses were performed. Spontaneous osteoclastogenesis in non-fractioned and T-cell depleted cultures of PBMC belonging to girls with high FSH levels was more evident than in cultures of subjects with normal FSH levels. In the former, osteoclastogenesis was sustained by monocytes expressing high levels of c-fms, TNF-α and RANK, and T-cells producing high RANKL and TNF-α; in the latter it was supported by T-cells expressing high RANKL levels. CD4(+)CD25(high) T-cells were reduced in all subjects, whereas CD3(+)/CD16(+)/CD56(+) NKT-cells were increased in those with high FSH levels. High RANKL and CTX levels were detected in the sera. Bone impairment was already detectable by DXA in subjects aged under 10, although it became more evident with aging. In conclusion, our results demonstrated that bone fragility in subjects with Turner's syndrome is associated to enhanced osteoclastogenesis. This process seems to be due to high FSH serum levels before HRT, whereas it is caused by high RANKL during

  18. Geotechnical Parameters of Alluvial Soils from in-situ Tests

    Science.gov (United States)

    Młynarek, Zbigniew; Stefaniak, Katarzyna; Wierzbicki, Jedrzej

    2012-10-01

    The article concentrates on the identification of geotechnical parameters of alluvial soil represented by silts found near Poznan and Elblag. Strength and deformation parameters of the subsoil tested were identified by the CPTU (static penetration) and SDMT (dilatometric) methods, as well as by the vane test (VT). Geotechnical parameters of the subsoil were analysed with a view to using the soil as an earth construction material and as a foundation for buildings constructed on the grounds tested. The article includes an analysis of the overconsolidation process of the soil tested and a formula for the identification of the overconsolidation ratio OCR. Equation 9 reflects the relation between the undrained shear strength and plasticity of the silts analyzed and the OCR value. The analysis resulted in the determination of the Nkt coefficient, which might be used to identify the undrained shear strength of both sediments tested. On the basis of a detailed analysis of changes in terms of the constrained oedometric modulus M0, the relations between the said modulus, the liquidity index and the OCR value were identified. Mayne's formula (1995) was used to determine the M0 modulus from the CPTU test. The usefullness of the sediments found near Poznan as an earth construction material was analysed after their structure had been destroyed and compacted with a Proctor apparatus. In cases of samples characterised by different water content and soil particle density, the analysis of changes in terms of cohesion and the internal friction angle proved that these parameters are influenced by the soil phase composition (Fig. 18 and 19). On the basis of the tests, it was concluded that the most desirable shear strength parameters are achieved when the silt is compacted below the optimum water content.

  19. Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein.

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    Devender Kumar

    2015-12-01

    Full Text Available Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d-/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint-proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin-binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration.

  20. The majority of lymphocytes in the bone marrow. Thymus and extrathymic T cells in the liver are generated in situ from their own preexisting precursors

    International Nuclear Information System (INIS)

    Parabiotic pairs of B6.Ly5.1 and B6.Ly5.2 mice were used to investigate how lymphocytes in various organs and various lymphocyte subsets mixed with partner cells. The origin of partner cells was determined by using anti-Ly5.1 mAb in conjunction with immunofluorescence tests. Parabiosis was also produced after the irradiation of B6.Ly5.2 mice at various doses to prepare an immunosuppressive partner. Irrespective of irradiation, lymphocytes and other hematopoietic cells in the bone marrow and lymphocytes in the thymus showed a low mixture of partner cells in comparison with those of all other organs tested. On the other hand, lymphocytes in the blood, spleen, and lymph nodes became a half-and-half mixture of their own cells and partner cell by 14 days after parabiosis. Among lymphocyte subsets, intermediate CD3 cells (i.e., CD3int cells) and NKT cells (i.e., NK1.1+ subset of CD3int cells) in the liver also showed a low mixture of partner cells. The present results raise the possibility that lymphocytes in the bone marrow and thymus, and extrathymic T cells in the liver might be in situ generated from their own preexisting precursor cells. Another observation was that, after irradiation, partner cells showed accelerated mixture even if they showed a low mixture under non-irradiated conditions. However, only lymphocyte subsets with the same phenotype as those of preexisting cells entered the corresponding sites. (author)