bluuebunny/crossref_metadata_2025_split huggingface dataset:
Killer Ig-Like Receptor (KIR) Genotype Predicts the Capacity of Human KIR-Positive CD56dim NK Cells to Respond to Pathogen-Associated Signals
Authors: Korbel Daniel S. , Norman Paul J. , Newman Kirsty C. , Horowitz Amir , Gendzekhadze Ketevan , Parham Peter , Riley Eleanor M. 
Published: May 2009

Abstract
IFN-γ emanating from NK cells is an important component of innate defense against infection. In this study, we demonstrate that, following in vitro stimulation of human peripheral blood NK cells with a variety of microbial ligands, CD56dim as well as CD56bright NK cells contribute to the overall NK cell IFN-γ response with, for most cell donors, IFN-γ+ CD56dim NK cells outnumbering IFN-γ+ CD56bright NK cells. We also observe that the magnitude of the human NK IFN-γ response to microbial ligands varies between individuals; that the antimicrobial response of CD56bright, but not CD56dim, NK cells is highly correlated with that of myeloid accessory cells; and that the ratio of IFN-γ+ CD56dim to IFN-γ+ CD56bright NK cells following microbial stimulation differs between individuals but remains constant for a given donor over time. Furthermore, ratios of IFN-γ+ CD56dim to IFN-γ+ CD56bright NK cells for different microbial stimuli are highly correlated and the relative response of CD56dim and CD56bright NK cells is highly significantly associated with killer Ig-like receptor (KIR) genotype. These data reveal an influence of KIR genotype, possibly mediated via NK cell education, on the ability of NK cells to respond to nonviral infections and have implications for genetic regulation of susceptibility to infection in humans.
Proinflammatory Adjuvants Enhance the Cognate Helper Activity of Aged CD4 T Cells
Authors: Maue Alexander C. , Eaton Sheri M. , Lanthier Paula A. , Sweet Kathryn B. , Blumerman Seth L. , Haynes Laura 
Published: May 2009

AbstractAge-related declines in humoral responses contribute to the reduced efficacy of vaccines in older populations. Using an adoptive transfer model, we have shown that age-related intrinsic declines in CD4 T cell function contribute significantly to the reduced humoral responses observed with aging, resulting in reduced B cell expansion and differentiation as well as reduced IgG production. In this current study, we show that the helper function of aged CD4 T cells can be enhanced using a TLR-binding adjuvant or an adjuvant containing proinflammatory (PI) cytokines. The helper function of aged CD4 T cells was also enhanced when PI cytokines were added during in vitro CD4 effector generation. Enhanced helper activity resulted in improved expansion and differentiation of B cells and affinity maturation of IgG. PI cytokines also induced significant production of effector cytokines, including IL-4, IFN-γ, IL-17, and IL-21, by both young and aged CD4 T cells. Importantly, we also show that proinflammatory adjuvants can significantly enhance the humoral response in intact aged animals. We propose that one of the mechanisms involved in the ability of adjuvants to enhance both young and aged T cell responses includes driving multifaceted T cell differentiation and production of multiple cytokines by responding CD4 T cells.
Protein Kinase D1 Is Essential for MyD88-Dependent TLR Signaling Pathway
Authors: Park Jeoung-Eun , Kim Young-In , Yi Ae-Kyung 
Published: May 2009

Abstract
Protein kinase D1 (PKD1) has been shown to be involved in certain MAPK activation and cytokine expression by several TLR ligands. However, the precise physiological role of PKD1 in individual signaling from TLRs has not been fully addressed. In this study, we provide evidence that PKD1 is being activated by TLR ligands, except the TLR3 ligand. PKD1 activation by TLR ligands is dependent on MyD88, IL-1R-associated kinase 4 and 1, but independent of TNF-α receptor-associated factor 6. PKD1-knockdown macrophages and bone marrow-derived dendritic cells revealed that PKD1 is indispensable for the MyD88-dependent ubiquitination of TNF-α receptor-associated factor 6; activation of TGF-β-activated kinase 1, MAPKs, and transcription factors; and expression of proinflammatory genes induced by TLR ligands, but is not involved in expression of type I IFNs induced by TLR ligands and TRIF-dependent genes induced by TLR3 and TLR4 ligands. These results demonstrate that PKD1 is essential for MyD88-dependent proinflammatory immune responses.
Sialoadhesin-Positive Macrophages Bind Regulatory T Cells, Negatively Controlling Their Expansion and Autoimmune Disease Progression
Authors: Wu Chuan , Rauch Uwe , Korpos Eva , Song Jian , Loser Karin , Crocker Paul R. , Sorokin Lydia M. 
Published: May 2009

Abstract
An important regulatory suppressive function in autoimmune and other inflammatory processes has been ascribed to CD4+Foxp3+ regulatory T cells (Tregs), which requires direct cell-cell communication between Tregs, effector T cells, and APCs. However, the molecular basis for these interactions has not yet been clarified. We show here that sialoadhesin (Sn), the prototype of the siglec family of sialic acid-binding transmembrane proteins, expressed by resident and activated tissue-infiltrating macrophages, directly binds to Tregs, negatively regulating their expansion in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In this model, macrophages infiltrate the CNS exhibiting tissue-destructing and demyelinating activity, leading to MS-like symptoms. We show here that severity of EAE symptoms is reduced in Sn knockout (KO) mice compared with wild-type littermates due to an up-regulation of CD4+Foxp3+ Treg lymphocytes. Through the use of a Sn fusion protein, Tregs were shown to express substantial amounts of Sn ligand on their cell surface, and direct interaction of Sn+ macrophages with Tregs specifically inhibited Treg but not effector T lymphocyte proliferation. Conversely, blocking of Sn on macrophages by Sn-specific Abs resulted in elevated proliferation of Tregs. Data indicate that Sn+ macrophages regulate Treg homeostasis which subsequently influences EAE progression. We propose a new direct cell-cell interaction-based mechanism regulating the expansion of the Tregs during the immune response, representing a “dialogue” between Sn+ macrophages and Sn-accessible sialic acid residues on Treg lymphocytes.
Dynamic Imaging of T Cell-Parasite Interactions in the Brains of Mice Chronically Infected withToxoplasma gondii
Authors: Schaeffer Marie , Han Seong-Ji , Chtanova Tatyana , van Dooren Giel G. , Herzmark Paul , Chen Ying , Roysam Badrinath , Striepen Boris , Robey Ellen A. 
Published: May 2009

AbstractThe intracellular parasite Toxoplasma gondii can establish persistent infection in the brain of a mammalian host, a standoff that involves the active participation of host CD8 T cells to control infection. CD8 T cells generally protect against intracellular pathogens by local delivery of effector molecules upon recognition of specific pathogen Ags on invaded host cells. However, the interactions between CD8 T cells, T. gondii, and APCs in the brain have not yet been examined. In this study we have used a mouse infection model in conjunction with two-photon microscopy of living brain tissue and confocal microscopy of fixed brain sections to examine the interactions between CD8 T cells, parasites, and APCs from chronically infected mice. We found that Ag-specific CD8 T cells were recruited to the brains of infected mice and persisted there in the presence of ongoing Ag recognition. Cerebral CD8 T cells made transient contacts with granuloma-like structures containing parasites and with individual CD11b+ APCs, including some that did not contain parasites. In contrast, T cells ignored intact Ag-bearing cysts and did not contact astrocytes or neurons, including neurons containing parasites or cysts. Our data represent the first direct observation of the dynamics of T cell-parasite interactions within living tissue and provide a new perspective for understanding immune responses to persistent pathogens in the brain.
Lentivector Immunization Stimulates Potent CD8 T Cell Responses against Melanoma Self-Antigen Tyrosinase-Related Protein 1 and Generates Antitumor Immunity in Mice
Authors: Liu Yanjun , Peng Yibing , Mi Michael , Guevara-Patino Jose , Munn David H. , Fu Ning , He Yukai 
Published: May 2009

Abstract
Recombinant lentivector immunization has been demonstrated to induce potent CD8 T cell responses in vivo. In this study, we investigated whether lentivector delivering a self/tumor Ag, tyrosinase related protein 1 (TRP1), could stimulate effective antitumor T cell responses. We found that immunization with lentivector expressing mutated TRP1 Ag elicited potent CD8 T cell responses against multiple TRP1 epitopes. Importantly, the activated CD8 T cells effectively recognize wild-type TRP1 epitopes. At peak times, as many as 10% of CD8 T cells were effector cells against TRP1 Ag. These cells killed wild-type TRP1 peptide-pulsed target cells in vivo and produced IFN-γ after ex vivo stimulation. The CD8 T cell responses were long-lasting (3–4 wk). Immunized mice were protected from B16 tumor cell challenge. In a therapeutic setting, lentivector immunization induced potent CD8 T cell responses in tumor bearing mice. The number of infiltrating T cells and the ratio of CD8/CD4 were dramatically increased in the tumors of immunized mice. The tumor-infiltrating CD8 T cells were functional and produced IFN-γ. The potent CD8 T cell responses stimulated by lentivector immunization eliminated small 3-day s.c. B16 tumors and strongly inhibited the growth of more established 5-day tumors. These studies demonstrate that genetic immunization with lentivector expressing mutated self/tumor Ag can generate potent CD8 T cell immune responses and antitumor immunity that prevent and inhibit B16 tumor growth, suggesting that lentivector immunization has the potential for tumor immunotherapy and immune prevention.
c-Maf Regulates IL-10 Expression during Th17 Polarization
Authors: Xu Jiangnan , Yang Yu , Qiu Guixing , Lal Girdhari , Wu Zhihong , Levy David E. , Ochando Jordi C. , Bromberg Jonathan S. , Ding Yaozhong 
Published: May 2009

Abstract
IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. Gene array analysis on Stat6 and T-bet double-deficient Th17 cells identified the Th2 transcription factor c-Maf to be synergistically up-regulated by IL-6 plus TGFβ and associated with Th17 IL-10 production. Both c-Maf and IL-10 induction during Th17 polarization depended on Stat3, but not Stat6 or Stat1, and mechanistically differed from IL-10 regulation by Th2 or IL-27 signals. TGFβ was also synergistic with IL-27 to induce c-Maf, and it induced Stat1-independent IL-10 expression in contrast to IL-27 alone. Retroviral transduction of c-Maf was able to induce IL-10 expression in Stat6-deficient CD4 and CD8 T cells, and c-Maf directly transactivated IL-10 gene expression through binding to a MARE (Maf recognition element) motif in the IL-10 promoter. Taken together, these data reveal a novel role for c-Maf in regulating T effector development, and they suggest that TGFβ may antagonize Th17 immunity by IL-10 production through c-Maf induction.
The Mucosal Adjuvant Effect of α-Galactosylceramide for Induction of Protective Immunity to Sexually Transmitted Viral Infection
Authors: Lindqvist Madelene , Persson Josefine , Thörn Karolina , Harandi Ali M. 
Published: May 2009

Abstract
Development of mucosal adjuvants to generate immunity in the female genital tract may have important implications for the development of vaccines to counter sexually transmitted infections. α-Galactosylceramide (α-GalCer) is presented by CD1d molecule on APCs to invariant Vα14+ NKT (iNKT) cells, which upon activation rapidly produce large amounts of immunomodulatory cytokines, leading to activation of a variety of innate and adaptive immune cells. Here, we assessed whether α-GalCer could act as a mucosal adjuvant for induction of protective immunity against genital herpes. We found that intranasal immunization with HSV-2 glycoprotein D (gD) in combination with α-GalCer elicits strong systemic gD-specific IgG Ab response as well as lymphoproliferative response with a mixed Th1/Th2 cytokine profile in the spleen, mediastinal lymph nodes, and genital lymph nodes. Importantly, such an immunization scheme conferred complete protection against an otherwise lethal vaginal HSV-2 challenge. We could also show that intravaginal immunization with gD plus α-GalCer generates potent gD-specific lymphoproliferative and IFN-γ responses in the genital lymph nodes and spleen. Furthermore, the vaginally immunized mice developed a strong systemic and mucosal IgG Ab response and protection against vaginal HSV-2 challenge. The mucosal adjuvant effect of α-GalCer was found to be mediated via CD1d molecule and appeared to be independent of the usage of the adaptor molecule MyD88. To our knowledge, this is the first report on the mucosal adjuvant effect of α-GalCer for induction of protective immunity against a sexually transmitted pathogen.
Shiga Toxin Activates Complement and Binds Factor H: Evidence for an Active Role of Complement in Hemolytic Uremic Syndrome
Authors: Orth Dorothea , Khan Abdul Basit , Naim Asma , Grif Katharina , Brockmeyer Jens , Karch Helge , Joannidis Michael , Clark Simon J. , Day Anthony J. , Fidanzi Sonja , Stoiber Heribert , Dierich Manfred P. , Zimmerhackl Lothar B. , Würzner Reinhard 
Published: May 2009

Abstract
Infections with enterohemorrhagic Escherichia coli (EHEC) are a major cause of hemolytic uremic syndrome (HUS). Shiga toxins (Stxs), especially Stx2, are believed to represent major virulence factors of EHEC, contributing to HUS pathogenesis. Beside EHEC-associated HUS, there are hereditary atypical forms of HUS, which are mostly caused by mutations of complement regulators. The aim of the present study was to investigate whether or not complement is also involved in the pathogenesis of EHEC-induced typical HUS, by being activated either directly or indirectly by involvement of its inhibitors. Purified Stx2 markedly activated complement via the alternative pathway and was found to bind to factor H (FH), however, only when it was active. No apparent cleavage or destruction of FH was visible, and cofactor activity in fluid phase was unaffected, but clearly delayed for surface-attached FH, where it is essential for host cell protection. Binding studies using FH constructs revealed that Stx2 binds to short consensus repeats (SCRs) 6–8 and SCRs18–20, but not to SCRs16–17, i.e., to regions involved in the surface recognition function of FH. In conclusion, complement, and in particular FH, not only plays an important role in atypical HUS, but most probably also in EHEC-induced HUS.
Adenovirus Vector-Induced Immune Responses in Nonhuman Primates: Responses to Prime Boost Regimens
Authors: Tatsis Nia , Lasaro Marcio O. , Lin Shih-Wen , Xiang Zhi Q. , Zhou Dongming , DiMenna Lauren , Li Hua , Bian Ang , Abdulla Sarah , Li Yan , Giles-Davis Wynetta , Engram Jessica , Ratcliffe Sarah J. , Silvestri Guido , Ertl Hildegund C. , Betts Michael R. 
Published: May 2009

Abstract
In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with preexisting neutralizing Abs against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine’s efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here, we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee-derived Ad vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the chimpanzee-derived Ad vectors induced higher T and B cell responses than did repeated immunizations with the AdHu5 vector, especially in AdHu5-preexposed macaques.
Cutting Edge: IL-23 Receptor GFP Reporter Mice Reveal Distinct Populations of IL-17-Producing Cells
Authors: Awasthi Amit , Riol-Blanco Lorena , Jäger Anneli , Korn Thomas , Pot Caroline , Galileos George , Bettelli Estelle , Kuchroo Vijay K. , Oukka Mohamed 
Published: May 2009

Abstract
IL-23, an IL-12 family member, has been implicated in the development of Th17 cells and the progression of autoimmune diseases. However, due to the lack of availability of sensitive Ab reagents specific for the IL-23 receptor (IL-23R), it has been difficult to characterize the cell types that express the IL-23R and are responsive to IL-23 in vivo. To address the role of IL-23 in vivo, we have generated a novel “knock-in” mouse in which we have replaced the intracellular domain of the IL-23R with the GFP. We show that in addition to Th17 cells, a subset of myeloid cells express IL-23R and respond to IL-23 by producing IL-17 and IL-22. Our studies further demonstrate that IL-23R expression is crucial for generation of encephalitogenic Th17 cells, but its expression on the innate immune system is dispensible in the development of experimental autoimmune encephalomyelitis.
Synthesis of the New 7S‐Aminolentiginosine and Derivatives
Authors: Cordero Franca M. , Bonanno Paola , Neudeck Sven , Vurchio Carolina , Brandi Alberto 
Published: April 2009

Abstractmagnified imageThe new 7S‐aminolentiginosine has been synthesized by a diastereoselective 1,3‐dipolar cycloaddition strategy starting from 3,4‐dihydroxylated pyrroline N‐oxides derived from L‐tartaric acid in thirteen steps. The intermediate 7S‐azidolentiginosine undergoes efficiently copper(I)‐catalysed Huisgen cycloadditions to alkynes.
Reaction of Bis(alkynyl)silanes with Tris(pentafluorophenyl)borane: Synthesis of Bulky Silole Derivatives by Means of 1,1‐Carboboration under Mild Reaction Conditions
Authors: Dierker Gereon , Ugolotti Juri , Kehr Gerald , Fröhlich Roland , Erker Gerhard 
Published: April 2009

Abstractmagnified imageThe strong Lewis acid tris(pentafluorophenyl)borane [B(C6F5)3] reacts rapidly with dimethylbis(phenylethynyl)silane (1c) at room temperature in toluene by shift of a pentafluorophenyl (C6F5) group and formation of a new carbon‐bis(pentafluorophenyl)boron linkage [CB(C6F5)2] in a sequence of 1,1‐carboboration reactions to yield the 4‐bis(pentafluorophenyl)boryl/3‐pentafluorophenyl‐substituted 1,1‐dimethyl‐2,5‐diphenylsilole derivative 7c. The analogous reaction of bis(trimethylsilylethynyl)diphenylsilane (1d) with tris(pentafluorophenyl)borane gave the corresponding boryl‐substituted silole derivative (7d) featuring six bulky substituents attached at the central heterocyclic framework. Both the starting materials (1c, 1d) and the products (7c, 7d) were characterized by X‐ray crystal structure analyses.
A Xenon‐129 Biosensor for Monitoring MHC–Peptide Interactions
Authors: Schlundt Andreas , Kilian Wolfgang , Beyermann Michael , Sticht Jana , Günther Sebastian , Höpner Sabine , Falk Kirsten , Roetzschke Olaf , Mitschang Lorenz , Freund Christian 
Published: April 2009

AbstractDie Komplexbildung zwischen einem Peptidliganden und einem MHC‐Klasse‐II‐Protein wird mithilfe eines 129Xe‐Biosensors nachgewiesen. Cryptophanmoleküle, die Xe‐Atome einfangen, werden mit einem Hämagglutinin(HA)‐Peptid modifiziert, das an das MHC‐Protein bindet. Die Wechselwirkung kann anhand einer Veränderung der chemischen Verschiebung von Käfig‐HA‐gebundenem 129Xe verfolgt werden.magnified image
Development of a Fluorescent Pb2+ Sensor
Authors: Marbella Lauren , Serli‐Mitasev Barbara , Basu Partha 
Published: April 2009

AbstractHochgefahren wird die Emissionsintensität des Heterocyclus 1 beim Binden an Pb2+. Damit fungiert 1 als niedermolekularer „Anschalt“‐Fluoreszenzsensor für Blei. Der Sensor ist hochselektiv und funktioniert über einen großen pH‐Bereich.magnified image
Linear π‐Acceptor‐Templated Dynamic Clipping to Macrobicycles and [2]Rotaxanes
Authors: Klivansky Liana M. , Koshkakaryan Gayane , Cao Dennis , Liu Yi 
Published: April 2009

AbstractSperr mich ein! Ein lineares, hantelförmiges Bipyridiniummolekül kann als Templat für die Bildung eines Käfigs um sich selbst herum mithilfe von sechs Iminbindungen wirken. Dabei entsteht als einziges Produkt ein verzahntes [2]Rotaxan (siehe Bild). Diese hocheffiziente [2+3]‐Klammerung tritt trotz der fehlenden Symmetrieähnlichkeit von Templat und gebildetem Makrobicyclus auf.magnified image
Titelbild: Ein substituentenfreier Galliumligand durch Hydrogenolyse von koordiniertem GaCp*: Synthese und Struktur des hoch fluktionalen [Ru2(Ga)(GaCp*)7(H)3] (Angew. Chem. 21/2009)
Authors: Cadenbach Thomas , Gemel Christian , Schmid Rochus , Halbherr Markus , Yusenko Kirill , Cokoja Mirza , Fischer Roland A. 
Published: May 2009

AbstractWeiche Schale, harter Kern ist das Grundprinzip für die Bildung einer Nanolegierung aus molekularen Vorstufen. Die gemeinsame Hydrogenolyse von Rutheniumkomplexen in Gegenwart von GaCp* führt zum isolierbaren Schlüsselintermediat [Ru2(Ga)(GaCp*)7 (H)3] mit einem substituentenfreien Gallium‐Brückenatom. Aus dieser “embryonalen” Spezies bilden sich unter vollständiger Abspaltung der Cp*‐Schutzhülle (im Bild als Eierschale dargestellt) Ru‐Ga‐Phasen, wie R. A. Fischer et al. in ihrer Zuschrift auf S. 3930 ff. beschreiben.magnified image
Innentitelbild: Giant Pores in a Chromium 2,6‐Naphthalenedicarboxylate Open‐Framework Structure with MIL‐101 Topology (Angew. Chem. 21/2009)
Authors: Sonnauer Andreas , Hoffmann Frank , Fröba Michael , Kienle Lorenz , Duppel Viola , Thommes Matthias , Serre Christian , Férey Gérard , Stock Norbert 
Published: May 2009

AbstractHoch poröse und stabile kristalline Gerüstverbindungen wurden unter Zuhilfenahme von Hochdurchsatzmethoden hergestellt, wie N. Stock et al. in ihrer Zuschrift auf S. 3849 ff. berichten. Eine zu MIL‐101 isoretikuläre Verbindung mit Zeolith‐analoger MTN‐Topologie und Käfigen mit 39 und 46 Å Durchmesser wurde durch Verwendung von 2,6‐Naphthalindicarbonsäure erhalten und konnte anhand von Struktursimulationen sowie elektronenmikroskopischen Daten und Sorptionsmessungen charakterisiert werden.magnified image
Linear π‐Acceptor‐Templated Dynamic Clipping to Macrobicycles and [2]Rotaxanes
Authors: Klivansky Liana M. , Koshkakaryan Gayane , Cao Dennis , Liu Yi 
Published: April 2009

AbstractCage me! A linear dumbbell‐shaped bipyridinium molecule can template cage formation around itself through sixfold imine bond formation to give an interlocked [2]rotaxane as the single product (see picture). This highly efficient [2+3] clipping occurs despite the symmetry mismatch between the template and the formed macrobicycle.magnified image
Spontaneous Formation of Giant Unilamellar Vesicles from Microdroplets of a Polyion Complex by Thermally Induced Phase Separation
Authors: Oana Hidehiro , Kishimura Akihiro , Yonehara Kei , Yamasaki Yuichi , Washizu Masao , Kataoka Kazunori 
Published: April 2009

AbstractWater pump: Polyion complex (PIC) vesicles are spontaneously formed from PIC microdroplets, which are formed by mixing cationic and anionic polymers (see picture). The formation process can be reversibly controlled by local heating with a focused infrared laser that triggers microphase separation and subsequent water influx. The size of the resulting giant unilamellar vesicles is determined by the initial size of the PIC droplets.magnified image