bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmacytoid DC promote priming of autoimmune Th17 cells and EAE
Authors: Isaksson Magnus , Ardesjö Brita , Rönnblom Lars , Kämpe Olle , Lassmann Hans , Eloranta Maija‐Leena , Lobell Anna 
Published: July 2009

AbstractEAE, an animal model for MS, is a Th17 and Th1‐cell‐mediated autoimmune disease, but the mechanisms leading to priming of encephalitogenic T cells in autoimmune neuroinflammation are poorly understood. To investigate the role of plasmacytoid DC (pDC) in the initiation of autoimmune Th17‐ and Th1‐cell responses and EAE, we depleted pDC with anti‐pDC Ag‐1 (anti‐PDCA1) mAb prior to immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein (MOG). pDC‐depleted mice developed less severe clinical and histopathological signs of EAE than control mice, which demonstrates a promoting role for pDC in the initiation of EAE. The levels of type I IFN were much lower in the sera from anti‐PDCA1‐treated mice. However, neutralization of type I IFN ameliorated the early phase of EAE but did not alter the severity of disease. Thus, only a minor part of the EAE‐promoting effect of pDC appears to be mediated by IFN‐α/β secretion. The numbers of MOG‐specific Th17 cells, but not Th1 cells, were lower in spleen from anti‐PDCA1‐treated mice compared with controls. In contrast, pDC depletion a week after MOG immunization resulted in more severe clinical signs of EAE. In conclusion, we demonstrate that pDC promote initiation of MOG‐induced Th17‐cell responses and EAE.
IL‐18 skews the invariant NKT‐cell population via autoreactive activation in atopic eczema
Authors: Lind Sara M. , Kuylenstierna Carlotta , Moll Markus , D. Jordö Emilie , Winqvist Ola , Lundeberg Lena , Karlsson Maria A. , T. Linder Maria , Johansson Catharina , Scheynius Annika , Sandberg Johan K. , Karlsson Mikael C. I. 
Published: July 2009

AbstractAtopic eczema (AE) is a chronic relapsing inflammatory skin disease where the commensal yeast Malassezia can act as a microbial trigger factor. Malassezia activates human DC to produce IL‐18, an innate cytokine that is elevated in serum of AE patients; however, the precise role of IL‐18 in human AE etiology is unknown. Herein, we investigated the effect of IL‐18 on the human invariant NKT (iNKT) cell compartment in AE. We found that IL‐18 was a potent activator of human iNKT‐cells and promoted a pro‐inflammatory CD1d‐dependent response, even in the absence of exogenous ligands. Chronic activation via IL‐18 on the other hand was inhibitory and skewed the iNKT‐cell pool by selectively suppressing CD4+ iNKT‐cells. This was mimicked in AE patients where the proportion of CD4+ iNKT‐cells was reduced in peripheral blood and coincided with elevated plasma levels of IL‐18. Furthermore, a reduced CD4+ iNKT‐cell pool was associated with elevated IgE levels in plasma, and the plasma levels of IL‐18 correlated with both total IgE and disease severity in the AE patients. Based on these findings, we propose that IL‐18‐mediated activation and subsequent dysregulation of the CD1d‐restricted iNKT‐cells plays a role in the pathogenesis of human AE.
The duration of TCR/pMHC interactions regulates CTL effector function and tumor‐killing capacity
Authors: Riquelme Erick , Carreño Leandro J. , González Pablo A. , Kalergis Alexis M. 
Published: July 2009

AbstractEffector CTL contribute to tumoral immunity by killing tumor cells through secretion of cytotoxic granules and cytokines. Activation of CTL requires specific recognition of cognate peptide‐MHC‐I (pMHC) complexes on the tumor cell surface by the CTL TCR. It has been suggested that the half‐life (t1/2) of the TCR/pMHC interaction modulates the activation of naïve CD8+ T cells; however, it remains unknown whether CTL effector function can also be regulated by the TCR/pMHC t1/2. Here, we have studied CTL activity in response to tumor cells loaded with pMHC that bind the TCR with different t1/2. We observed that the TCR/pMHC t1/2 can differentially regulate CTL effector function during the interaction with tumor cells and defines the nature of anti‐tumoral CTL responses in vivo. Although prolonged TCR/pMHC t1/2 promoted only partial expression of cytotoxic molecules, short t1/2 induced partial polarization of lytic machinery toward target cells. In contrast, intermediate TCR/pMHC t1/2 induced strong expression of cytotoxic molecules, efficient polarization of lytic machinery and subsequent release of toxic granules by CTL that killed tumor cells. Consistently, efficient in vivo CTL‐mediated tumor clearance was only observed for tumors expressing intermediate t1/2 pMHC ligands. These data suggest that there is an optimal TCR/pMHC t1/2 for efficient CTL activity.
Homeostatic proliferation and survival of naïve and memory T cells
Authors: Boyman Onur , Létourneau Sven , Krieg Carsten , Sprent Jonathan 
Published: July 2009

AbstractThe immune system relies on homeostatic mechanisms in order to adapt to the changing requirements encountered during steady‐state existence and activation by antigen. For T cells, this involves maintenance of a diverse repertoire of naïve cells, rapid elimination of effector cells after pathogen clearance, and long‐term survival of memory cells. The reduction of T‐cell counts by either cytotoxic drugs, irradiation, or certain viruses is known to lead to lymphopenia‐induced proliferation and restoration of normal T‐cell levels. Such expansion is governed by the interaction of TCR with self‐peptide/MHC (p/MHC) molecules plus contact with cytokines, especially IL‐7. These same ligands, i.e. p/MHC molecules and IL‐7, maintain naïve T lymphocytes as resting cells under steady‐state T‐cell‐sufficient conditions. Unlike naïve cells, typical “central” memory T cells rely on a combination of IL‐7 and IL‐15 for their survival in interphase and for occasional cell division without requiring signals from p/MHC molecules. Other memory T‐cell subsets are less quiescent and include naturally occurring activated memory‐phenotype cells, memory cells generated during chronic viral infections, and effector memory cells. These subsets of activated memory cells differ from central memory T cells in their requirements for homeostatic proliferation and survival. Thus, the factors controlling T‐cell homeostasis can be seen to vary considerably from one subset to another as described in detail in this review.
Memory B cells: Effectors of long‐lived immune responses
Authors: Tangye Stuart G. , Tarlinton David M. 
Published: July 2009

AbstractImmunological memory is the phenomenon whereby B and T cells have the unique ability to respond with heightened kinetics and efficacy to subsequent encounter with Ag relative to the initial exposure. In this review, we examine recent developments in the phenotypic characterisation of memory B cells, with an emphasis on the definition and functional properties of memory B‐cell subsets in humans. Gene expression differences are also considered in light of the unique functional and survival properties of memory B cells, and mutations that alter memory formation and function are also examined. Finally, we consider recent advances in the understanding of germinal center B‐cell differentiation through analysis of transcription factor networks operating in these B cells.
Vaccination with an adenoviral vector encoding the tumor antigen directly linked to invariant chain induces potent CD4+ T‐cell‐independent CD8+ T‐cell‐mediated tumor control
Authors: Sorensen Maria R. , Holst Peter J. , Pircher Hanspeter , Christensen Jan P. , Thomsen Allan R. 
Published: July 2009

AbstractAntigen‐specific immunotherapy is an attractive strategy for cancer control. In the context of antiviral vaccines, adenoviral vectors have emerged as a favorable means for immunization. Therefore, we chose a strategy combining use of these vectors with another successful approach, namely linkage of the vaccine antigen to invariant chain (Ii). To evaluate this strategy we used a mouse model, in which an immunodominant epitope (GP33) of the LCMV glycoprotein (GP) represents the tumor‐associated neoantigen. Prophylactic vaccination of C57BL/6 mice with a replication‐deficient human adenovirus 5 vector encoding GP linked to Ii (Ad‐Ii‐GP) resulted in complete protection against GP33‐expressing B16.F10 tumors. Therapeutic vaccination with Ad‐Ii‐GP delayed tumor growth by more than 2 wk compared with sham vaccination. Notably, therapeutic vaccination with the linked vaccine was significantly better than vaccination with adenovirus expressing GP alone (Ad‐GP), or GP and Ii unlinked (Ad‐GP+Ii). Ad‐Ii‐GP‐ induced tumor control depended on an improved generation of the tumor‐associated neoantigen‐specific CD8+ T‐cell response and was independent of CD4+ T cells. IFN‐γ was shown to be a key player during the tumor degradation. Finally, Ad‐Ii‐GP but not Ad‐GP vaccination can break the immunological non‐reactivity in GP transgenic mice indicating that our vaccine strategy will prove efficient also against endogenous tumor antigens.
Generating memory with vaccination
Authors: Castellino Flora , Galli Grazia , Del Giudice Giuseppe , Rappuoli Rino 
Published: July 2009

AbstractThe goal of vaccination is to induce long‐lasting protective immune memory. Although most vaccines induce good memory responses, the type of memory induced by different vaccines may be considerably different. In addition, memory responses to the same vaccine may be influenced by age, environmental and genetic factors. Results emerging from detailed and integrated profiling of immune‐responses to natural infection or vaccination suggest that the type and duration of immune memory are largely determined by the magnitude and complexity of innate immune signals that imprint the acquired immune primary responses. Here we summarize results obtained from analyzing human immune memory responses to different types of vaccines. We will also discuss how extending clinical investigation to events occurring early after vaccination can help identify early predictive markers of protective memory and thus contribute to faster development of better and safer vaccines.
Making and circumventing tolerance to cancer
Authors: Kammertoens Thomas , Blankenstein Thomas 
Published: July 2009

AbstractThe interactions between cancer and immune cells are complex. Even though the mutations that cause cancer can create new antigens that are potentially “visible” to T cells, in most experimental model systems the growth of tumors is accompanied by induction of T‐cell tolerance towards the tumor. How tolerance to tumors is induced and how tolerance can be broken by immunotherapy have been a main focus in cancer immunology. Here, we discuss experimental models used in cancer immunology. We argue that, while it is obviously easy for tumors to induce tolerance, it should be as easy to circumvent tolerance by the adoptive transfer of tumor‐antigen‐reactive T cells. Effective adoptive T‐cell therapy has become feasible by methods to identify TCR against tumor‐associated (self‐) antigens with high affinity and to graft a new antigen specificity to patients' T cells by TCR gene transfer.
TLR2 engagement on memory CD8+ T cells improves their cytokine‐mediated proliferation and IFN‐γ secretion in the absence of Ag
Authors: Cottalorda Anne , Mercier Blandine C. , Mbitikon‐Kobo Florentin M. , Arpin Christophe , Teoh Denise Y. L. , McMichael Andrew , Marvel Jacqueline , Bonnefoy‐Bérard Nathalie 
Published: July 2009

AbstractPersistence of memory CD8+ T cells is known to be largely controlled by common gamma chain cytokines, such as IL‐2, IL‐7 and IL‐15. However, other molecules may be involved in this phenomenon. We show here that TLR2−/− mice have a decreased frequency of memory phenotype CD8+ T cells when compared with WT mice. This prompted us to investigate the role of TLR2 in the homeostasis of memory CD8+ T cells. We describe here a new TLR2‐dependent mechanism which, in the absence of specific antigen, directly controls memory CD8+ T‐cell proliferation and IFN‐γ secretion. We demonstrate that TLR2 engagement on memory CD8+ T cells increases their proliferation and expansion induced by IL‐7 both in vitro and in vivo. We also show that TLR2 ligands act in synergy with IL‐2 to induce IFN‐γ secretion in vitro. Both conclusions are obtained with spontaneously arising memory phenotype and antigen‐specific memory CD8+ T cells. Altogether, our data support the idea that continuous TLR2 signaling in response to microbial stimuli or endogenous danger signals might directly contribute to the maintenance of the diversity memory CD8+ T cells in the organism.
Development and maturation of invariant NKT cells in the presence of lysosomal engulfment
Authors: Plati Tiziana , Visigalli Ilaria , Capotondo Alessia , Buono Mario , Naldini Luigi , Cosma Maria Pia , Biffi Alessandra 
Published: July 2009

AbstractA defect in invariant NKT (iNKT) cell selection was hypothesized in lysosomal storage disorders (LSD). Accumulation of glycosphingolipids (GSL) in LSD could influence lipid loading and/or presentation causing entrapment of endogenous ligand(s) within storage bodies or competition of the selecting ligand(s) by stored lipids for CD1d binding. However, when we analyzed the iNKT cell compartment in newly tested LSD animal models that accumulate GSL, glycoaminoglycans or both, we observed a defective iNKT cell selection only in animals affected by multiple sulfatase deficiency, in which a generalized aberrant T‐cell development, rather than a pure iNKT defect, was present. Mice with single lysosomal enzyme deficiencies had normal iNKT cell development. Thus, GSL/glycoaminoglycans storage and lysosomal engulfment are not sufficient for affecting iNKT cell development. Rather, lipid ligand(s) or storage compounds, which are affected in those LSD lacking mature iNKT cells, might indeed be relevant for iNKT cell selection.
Diverse regulatory roles for lysosomal proteases in the immune response
Authors: Colbert Jeff D. , Matthews Stephen P. , Miller Gail , Watts Colin 
Published: July 2009

AbstractThe innate and adaptive immune system utilise endocytic protease activity to promote functional immune responses. Cysteine and aspartic proteases (cathepsins) constitute a subset of endocytic proteases, the immune function of which has been described extensively. Although historically these studies have focused on their role in processes such as antigen presentation and zymogen processing within the endocytic compartment, recent discoveries have demonstrated a critical role for these proteases in other intracellular compartments, and within the extracellular milieu. It has also become clear that their pattern of expression and substrate specificities are more diverse than was first envisaged. Here, we discuss recent advances addressing the role of lysosomal proteases in various aspects of the immune response. We pay attention to reports demonstrating cathepsin activity outside of its canonical endosome/lysosome microenvironment.
Triphenylamine‐Based Pyridine N‐Oxide and Pyridinium Salts for Size‐Selective Recognition of Dicarboxylates
Authors: Ghosh Kumaresh , Masanta Goutam , Chattopadhyay Asoke P. 
Published: July 2009

AbstractTriphenylamine‐based receptors 1–3 have been designed and synthesized for the recognition of dicarboxylates. The correct dispositions of the binding groups in both 1 and 2 under 4,4′‐dicarbonyltriphenylamine spacer enable them to bind aliphatic dicarboxylates of different chain lengths with moderate binding constant values. In the binding event, triphenylamine‐based pyridinium salt 2 is found to be more effective than triphenylamine‐based pyridine N‐oxide 1 and shows selectivity for long‐chain pimelate. Binding takes place at charged sites with concomitant PET‐based (photo‐induced electron transfer) quenching of emission of triphenylamine motif. The binding was monitored in DMSO using 1H NMR, UV/Vis and fluorescence spectroscopic methods. Efficiency of pyridinium binding site over the others in the present study has been rationalised by invoking theoretical results. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Stereoselective Synthesis of New Ferrocene‐Derived Amino Acid Building Blocks
Authors: Hunold Andrea , Neundorf Ines , James Philippe , Neudörfl Jörg , Schmalz Hans‐Günther 
Published: July 2009

AbstractAs a contribution to bioorganometallic chemistry, a dia‐ and enantioselective synthesis of novel carbocyclic amino acid analogues with a 1,2‐ferroceno‐fused cyclopentene backbone has been developed. Using two related planar‐chiral intermediates, i.e. (1S,E)‐ethyl‐3‐[2‐(phenylsulfonylacetyl)ferrocen‐1‐yl]acrylate, (1S,E)‐ethyl‐3‐[2‐(methoxycarbonyl)ferrocen‐1‐yl]acrylate, stereoselective entries to different tBoc‐ or Fmoc‐protected ferroceno‐fused 1‐amino‐3‐carboxyalkyl‐2‐cyclopentenes were elaborated. These compounds were then used for the preparation of metal‐containing peptides by means of solid‐phase peptide synthesis (SPPS). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Bismalonates Constructed on a Hexaphenylbenzene Scaffold for the Synthesis of Equatorial Fullerene Bisadducts (Eur. J. Org. Chem. 23/2009)
Authors: Figueira‐Duarte Teresa M. , Gégout Aline , Olivier Jean , Cardinali François , Nierengarten Jean‐François 
Published: July 2009

AbstractThe cover picture shows a sun‐shaped hexaphenylbenzene unit shining over the equator of a fullerene spheroid. This macrocyclic fullerene bisadduct with an equatorial addition pattern was obtained with excellent regioselectivity from the reaction of C60 with a bismalonate constructed on a hexaphenylbenzene scaffold. Details are discussed in the article by J.‐F. Nierengarten et al. on p. 3879 ff.
Differentiation of green tea samples by chiral CD‐MEKC analysis of catechins content
Authors: Gotti Roberto , Furlanetto Sandra , Lanteri Silvia , Olmo Stefano , Ragaini Alessandro , Cavrini Vanni 
Published: July 2009

AbstractA chiral CD‐MEKC method, enantioselective for catechin and gallocatechin, was developed, validated and applied to the analysis of tea samples. The method was addressed to the fast and simultaneous quantitation of the most represented and biologically important green tea catechins and methylxanthines. The CD‐MEKC was based on SDS as surfactant (90 mM) and hydroxypropyl‐β‐CD (25 mM) as chiral selector, under acidic conditions (25 mM borate–phosphate buffer, pH 2.5). The method was first applied to study the thermal epimerisation of epi‐structured catechins, (−)‐epicatechin and (−)‐epigallocatechin, to non‐epi‐structured (−)‐catechin and (−)‐gallocatechin. The latter compounds, being non‐native molecules, were for the first time regarded as useful phytomarkers of tea samples subjected to thermal treatment. The proposed method was applied to the analysis of more than twenty tea samples of different geographical origins (China, Japan, Ceylon), having undergone different storage conditions and manufacturing processes. Finally, factor analysis was used to visualise the useful information contained in the data set, showing that it was possible to distinguish tea samples on the basis of their different contents of native and non‐native catechins.
Enantioseparation by MEKC using a ligand exchange‐based chiral pseudostationary phase
Authors: Zaher Mustapha , Ravelet Corinne , Vanhaverbeke Cecile , Baussanne Isabelle , Perrier Sandrine , Fize Jennifer , Décout Jean‐Luc , Peyrin Eric 
Published: July 2009

AbstractIn this paper, a new ligand‐exchange ‐MEKC mode, based on the design of a unique lipohilic species (4′‐octadecylneamine derivative), which served both as micelle‐forming surfactant (by its hydrophobic part) and central ion‐complexing ligand (by its hydrophilic part) is described. The CMC of the used lipophilic neamine derivative was first determined by surface tension measurements. Subsequent NMR experiments were performed in order to investigate the Cu(II) binding properties of the neamine micellar phase. The enantioseparation properties of both the octadecylneamine derivative‐Cu(II) MEKC and the native neamine‐Cu(II) CE systems were evaluated and compared using the tryptophan racemate as a probe analyte. The effects of several different electrophoretic conditions on the enantiomer migration behavior in the ligand‐exchange‐MEKC mode were examined. The developed methodology was also applied to the enantioseparation of other analytes such as 1‐methyl‐tryptophan, 3,5‐diiodo‐tyrosine and 1‐naphtyl‐alanine.
Transient ζ‐potential measurements in hydrophobic, TOPAS microfluidic substrates
Authors: Tandon Vishal , Bhagavatula Sharath K. , Kirby Brian J. 
Published: July 2009

AbstractWe utilize time‐resolved electrokinetic measurements in order to study the electrokinetic properties of silica and TOPAS microfluidic channels as a function of the time history of the fluid–solid interface. In pressure‐driven flow through TOPAS microchannels, the ζ‐potential as inferred from streaming potential measurements decays exponentially by a factor of 1.5 with a characteristic decay time of 3 h after the initial formation of the fluid–solid interface. A similar exponential decay is observed immediately after water is exchanged for ethanol as the solvent in the system. In electroosmotically driven flow through TOPAS microchannels, the ζ‐potential as inferred through current monitoring experiments was constant in time. No electrokinetic transients were observed in silica microchannels under these flow conditions.
Determination of cyanobacterial cyclic peptide hepatotoxins in drinking water using CE
Authors: Birungi Grace , Yau Li Sam Fong 
Published: July 2009

AbstractFour cyanobacteria hepatotoxins microcystin LR, microcystin RR, microcystin YR, and nodularin were simultaneously determined in drinking water using CZE and MEKC coupled with UV detection. The toxins were satisfactorily separated in both CZE and MEKC modes. Detection limits were in the range of 0.82–4.81 μg/mL, with R2 values of 0.994–0.999. The linearity range tested for the standards was 5–100 μg/mL and RSD percentages were in the range of 1.0–2.5% for retention time and 3.0–10.2% for peak area. When a known amount of standard was spiked into a known volume of water and extracted, recoveries were 90.3% (RR), 101.5% (nodularin), 90.6% (YR), and 88.2% (LR). The use of SPE enabled cleanup and pre‐concentration of a real sample to achieve a 100‐fold concentration factor. Detection limits after SPE of the real sample spiked with microcystins were 0.090 μg/L (RR), 0.076 μg/L (YR), and 0.110 μg/L (LR), with RSD percentage values of 9.9–11.7% for peak area and 2.2–3.3% for retention time. The technique developed provides an alternative method for determining microcystins at levels of concentration that will be able to meet WHO drinking water guidelines for microcystins.