bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fascin Is Involved in the Antigen Presentation Activity of Mature Dendritic Cells
Authors: Al-Alwan Monther M. , Rowden Geoffrey , Lee Timothy D. G. , West Kenneth A. 
Published: April 2014

AbstractMaturation of dendritic cells (DC) is critical to their development into potent APCs. Upon maturation, DC up-regulate the expression of MHC class II as well as costimulatory and adhesion molecules, all of which are important in Ag presentation. In addition, they undergo structural changes characterized by the expression of numerous long dendrites. Fascin is an actin-bundling protein that has been reported to be important for the development of dendrites. In this study, we evaluated fascin expression and function during DC maturation into potent APC. In vitro, treatment of bone marrow-derived DC (BM-DC) with GM-CSF resulted in increased levels of fascin expression. This increase correlated directly with an increase in MHC class II and B7-2 expression. Fascin expression was decreased by the addition of TGF-β and increased by the addition TNF-α to the culture. These cytokines suppress or enhance DC maturation, respectively. Increased levels of fascin expression were found to correlate with increased APC activity in a one-way MLR. Specific inhibition of fascin expression, using antisense oligonucleotides, markedly reduced this APC allostimulatory activity. These data demonstrate that fascin expression correlates with DC maturation into APC, and it plays a significant role in the ability of DC to function as APC. This observation is the first evidence linking fascin-mediated dendrite formation with the APC activity of DC.
T Lymphocytes Promote the Development of Bone Marrow-Derived APC in the Central Nervous System
Authors: Subramanian Sandhya , Bourdette Dennis N. , Corless Christopher , Vandenbark Arthur A. , Offner Halina , Jones Richard E. 
Published: April 2014

AbstractCertain cells within the CNS, microglial cells and perivascular macrophages, develop from hemopoietic myelomonocytic lineage progenitors in the bone marrow (BM). Such BM-derived cells function as CNS APC during the development of T cell-mediated paralytic inflammation in diseases such as experimental autoimmune encephalomyelitis and multiple sclerosis. We used a novel, interspecies, rat-into-mouse T cell and/or BM cell-transfer method to examine the development and function of BM-derived APC in the CNS. Activated rat T cells, specific for either myelin or nonmyelin Ag, entered the SCID mouse CNS within 3–5 days of cell transfer and caused an accelerated recruitment of BM-derived APC into the CNS. Rat APC in the mouse CNS developed from transferred rat BM within an 8-day period and were entirely sufficient for induction of CNS inflammation and paralysis mediated by myelin-specific rat T cells. The results demonstrate that T cells modulate the development of BM-derived CNS APC in an Ag-independent fashion. This previously unrecognized regulatory pathway, governing the presence of functional APC in the CNS, may be relevant to pathogenesis in experimental autoimmune encephalomyelitis, multiple sclerosis, and/or other CNS diseases involving myelomonocytic lineage cells.
RAG1 and RAG2 Expression by B Cell Subsets from Human Tonsil and Peripheral Blood
Authors: Girschick Hermann J. , Grammer Amrie C. , Nanki Toshihiro , Mayo Marlyn , Lipsky Peter E. 
Published: April 2014

AbstractIt has been suggested that B cells acquire the capacity for secondary V(D)J recombination during germinal center (GC) reactions. The nature of these B cells remains controversial. Subsets of tonsil and blood B cells and also individual B cells were examined for the expression of recombination-activating gene (RAG) mRNA. Semiquantitative analysis indicated that RAG1 mRNA was present in all tonsil B cell subsets, with the largest amount found in naive B cells. RAG2 mRNA was only found in tonsil naive B cells, centrocytes, and to a lesser extent in centroblasts. Neither RAG1 nor RAG2 mRNA was routinely found in normal peripheral blood B cells. In individual tonsil B cells, RAG1 and RAG2 mRNAs were found in 18% of naive B cells, 22% of GC founder cells, 0% of centroblasts, 13% of centrocytes, and 9% of memory B cells. Individual naive tonsil B cells containing both RAG1 and RAG2 mRNA were activated (CD69+). In normal peripheral blood ∼5% of B cells expressed both RAG1 and RAG2. These cells were uniformly postswitch memory B cells as documented by the coexpression of IgG mRNA. These results indicate that coordinate RAG expression is not found in normal peripheral naive B cells but is up-regulated in naive B cells which are activated in the tonsil. With the exception of centroblasts, RAG1 and RAG2 expression can be found in all components of the GC, including postswitch memory B cells, some of which may circulate in the blood of normal subjects.
A Novel Chicken Membrane-Associated Complement Regulatory Protein: Molecular Cloning and Functional Characterization
Authors: Inoue Naokazu , Fukui Aya , Nomura Midori , Matsumoto Misako , Toyoshima Kumao , Seya Tsukasa 
Published: April 2014

AbstractA cDNA encoding a membrane-associated complement (C) regulatory protein was identified here for the first time in an oviparous vertebrate, chicken. This protein, named Cremp, possessed five short consensus repeats (SCRs) and one SCR-like domain followed by a transmembrane domain and a cytoplasmic tail. SCR1/SCR2 of Cremp were 43.6% identical with SCR2/SCR3 of human decay-accelerating factor (CD55), and SCR3/SCR4 were 45.3% identical with those of human membrane cofactor protein (CD46). Cremp is likely to be an ancestral hybrid protein of human decay-accelerating factor and membrane cofactor protein rather than a homolog of rodent C receptor 1-related protein y, which structurally resembles human CR1 (CD35). Chinese hamster ovary cells transfected with Cremp were efficiently protected from chicken C but not from human or rabbit C in both classical and alternative pathways. Thus, chicken Cremp is a membrane C regulator for cell protection against homologous C. Cremp mRNA was seen as a doublet comprised of a faint band of 2.2 kb and a thick band of 3.0 kb on RNA blotting analysis. An Ab against chicken Cremp recognized a single band of 46.8 kDa on immunoblotting. mRNA and protein of Cremp were ubiquitously expressed in all chicken organs tested. Minute amounts of dimer were present in some tissues. Surface expression of Cremp was confirmed by flow cytometry and immunofluorescence analysis. These results suggested that even in nonmammals a C regulatory membrane protein with ubiquitous tissue distribution should be a prerequisite for protection of host cells from homologous C attack.
Classically Restricted Human CD8+ T Lymphocytes Derived fromMycobacterium tuberculosis-Infected Cells: Definition of Antigenic Specificity
Authors: Lewinsohn David M. , Zhu Liqing , Madison Valerie J. , Dillon Davin C. , Fling Steven P. , Reed Steven G. , Grabstein Kenneth H. , Alderson Mark R. 
Published: April 2014

AbstractPrevious studies in murine and human models have suggested an important role for HLA Ia-restricted CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). Therefore, understanding the Ags presented via HLA-Ia will be important in understanding the host response to Mtb and in rational vaccine design. We have used monocyte-derived dendritic cells in a limiting dilution analysis to generate Mtb-specific CD8+ T cells. Two HLA-Ia-restricted CD8+ T cell clones derived by this method were selected for detailed analysis. One was HLA-B44 restricted, and the other was HLA-B14 restricted. Both were found to react with Mtb-infected, but not bacillus Calmette-Guérin-infected, targets. For both these clones, the Ag was identified as culture filtrate protein 10 (CFP10)/Mtb11, a 10.8-kDa protein not expressed by bacillus Calmette-Guérin. Both clones were inhibited by the anti-class I Ab and anti-HLA-B,C Abs. Using a panel of CFP10/Mtb11-derived 15-aa peptides overlapping by 11 aa, the region containing the epitopes for both clones has been defined. Minimal 10-aa epitopes were defined for both clones. CD8+ effector cells specific for these two epitopes are present at high frequency in the circulating pool. Moreover, the CD8+ T cell response to CFP10/Mtb11 can be largely accounted for by the two epitopes defined herein, suggesting that this is the immunodominant response for this purified protein derivative-positive donor. This study represents the first time CD8+ T cells generated against Mtb-infected APC have been used to elucidate an Mtb-specific CD8+ T cell Ag.
Lipoprotein Access to MHC Class I Presentation During Infection of Murine Macrophages with Live Mycobacteria
Authors: Neyrolles Olivier , Gould Keith , Gares Marie-Pierre , Brett Sara , Janssen Riny , O’Gaora Peadar , Herrmann Jean-Louis , Prévost Marie-Christine , Perret Emmanuelle , Thole Jelle E. R. , Young Douglas 
Published: April 2014

AbstractFollowing uptake by macrophages, live mycobacteria initially reside within an immature phagosome that resists acidification and retains access to recycling endosomes. Glycolipids are exported from the mycobacterial phagosome and become available for immune recognition by CD1-restricted T cells. The aim of this study was to explore the possibility that lipoproteins might similarly escape from the phagosome and act as immune targets in cells infected with live mycobacteria. We have focused on a 19-kDa lipoprotein from Mycobacterium tuberculosis that was previously shown to be recognized by CD8+ T cells. The 19-kDa Ag was found to traffic separately from live mycobacteria within infected macrophages by a pathway that was dependent on acylation of the protein. When expressed as a recombinant protein in rapid-growing mycobacteria, the 19-kDa Ag was able to deliver peptides for recognition by MHC class I-restricted T cells by a TAP-independent mechanism. Entry into the class I pathway was rapid, dependent on acylation, and could be blocked by killing the mycobacteria by heating before infection. Although the pattern of 19-kDa trafficking was similar with different mycobacterial species, preliminary experiments suggest that class I presentation is more efficient during infection with rapid-growing mycobacteria than with the slow-growing bacillus Calmette-Guérin vaccine strain.
Biased Vβ Usage in Immature Thymocytes Is Independent of DJβ Proximity and pTα Pairing
Authors: Wilson Anne , Maréchal Céline , MacDonald H. Robson 
Published: April 2014

AbstractDuring thymus development, the TCR β locus rearranges before the TCR α locus. Pairing of productively rearranged TCR β-chains with an invariant pTα chain leads to the formation of a pre-TCR and subsequent expansion of immature pre-T cells. Essentially nothing is known about the TCR Vβ repertoire in pre-T cells before or after the expression of a pre-TCR. Using intracellular staining, we show here that the TCR Vβ repertoire is significantly biased at the earliest developmental stage in which VDJβ rearrangement has occurred. Moreover (and in contrast to the VH repertoire in immature B cells), Vβ repertoire biases in immature T cells do not reflect proximity of Vβ gene segments to the DJβ cluster, nor do they depend upon preferential Vβ pairing with the pTα chain. We conclude that V gene repertoires in developing T and B cells are controlled by partially distinct mechanisms.
Activation of Extracellular Signal-Regulated Kinases, NF-κB, and Cyclic Adenosine 5′-Monophosphate Response Element-Binding Protein in Lung Neutrophils Occurs by Differing Mechanisms After Hemorrhage or Endotoxemia
Authors: Abraham Edward , Arcaroli John , Shenkar Robert 
Published: April 2014

AbstractAcute lung injury is frequently associated with sepsis or blood loss and is characterized by a proinflammatory response and infiltration of activated neutrophils into the lungs. Hemorrhage or endotoxemia result in activation of cAMP response element-binding protein (CREB) and NF-κB in lung neutrophils as well as increased expression of proinflammatory cytokines, such as TNF-α and macrophage-inflammatory peptide-2, by these cells. Activation of the extracellular regulated kinase (ERK) pathway occurs in stress responses and is involved in CREB activation. In the present experiments, hemorrhage or endotoxemia produced increased activation of mitogen-activated protein kinase kinase (MEK)1/2 and ERK2 (p42), but not of ERK1 (p44), in lung neutrophils. ERK1, ERK2, and MEK1/2 were not activated in peripheral blood neutrophils after hemorrhage or endotoxemia. Inhibition of xanthine oxidase led to further increase in the activation of MEK1/2 and ERK2 in lung neutrophils after hemorrhage, but not after endotoxemia. α-Adrenergic blockade before hemorrhage resulted in increased activation in lung neutrophils of MEK1/2, ERK1, ERK2, and CREB, but decreased activation of NF-κB. In contrast, α-adrenergic blockade before endotoxemia was associated with decreased activation of MEK1/2, ERK2, and CREB, but increased activation of NF-κB. β-Adrenergic blockade before hemorrhage did not alter MEK1/2 or ERK1 activation in lung neutrophils, but decreased activation of ERK2 and CREB, while increasing activation of NF-κB. β-Adrenergic inhibition before endotoxemia did not affect activation of MEK1/2, ERK1, ERK2, CREB, or NF-κB. These data indicate that the pathways leading to lung neutrophil activation after hemorrhage are different from those induced by endotoxemia.
Annexin V Binds to Positively Selected B Cells
Authors: Dillon Stacey R. , Constantinescu Andrei , Schlissel Mark S. 
Published: April 2014

AbstractRecombinant annexin V (rAnV) has been used in flow cytometry to identify cells undergoing apoptosis, based on its ability to bind to phosphatidylserine, a negatively charged lipid normally restricted to the cytoplasmic face of the plasma membrane but externalized early during apoptosis. When we stained murine bone marrow (BM) cells with fluorescently labeled rAnV, we found that a surprisingly large fraction of BM B cells bearing selectable transgenic Ag receptors bind significant amounts of rAnV, but that these cells are not apoptotic. Here, we show that binding of rAnV to developing B cells in normal mice correlates with B cell receptor-dependent selection events at several stages of development within both B-1 and B-2 cell subsets. In fact, nearly all B-1 B cells and splenic marginal zone B cells bind rAnV, suggesting that the externalization of phosphatidylserine occurs once mature B cells are selected through BCR-mediated signaling. However, this plasma membrane alteration is apparently not shared by all lymphocytes, because we did not find a parallel population of rAnV-binding viable T cells in vivo in normal or TCR transgenic mice. We also show that BM stromal cell lines can influence the extent of rAnV binding by viable BM B cells during coculture in vitro. We suggest that rAnV detects a potentially important membrane alteration that occurs as B cells develop in the BM and are readied for export to the peripheral lymphoid organs and again among mature B cells recruited to the marginal zone or the B-1 compartment.
p38 Mitogen-Activated Protein Kinase Inhibition Increases Cytokine Release by Macrophages In Vitro and During Infection In Vivo
Authors: van den Blink Bernt , Juffermans Nicole P. , ten Hove Tessa , Schultz Mark J. , van Deventer Sander J. H. , van der Poll Tom , Peppelenbosch Maikel P. 
Published: April 2014

Abstractp38 mitogen-activated protein kinase (MAPK) has been suggested as a mediator of cytokine release and is currently being targeted for anti-inflammatory therapy. However, experimental data are contradictory and lack sufficient affirmation in vivo. We tested the effect of p38 MAPK inhibition in several cell types and in different murine models of infectious disease. We observed that most cell types react to p38 MAPK inhibition with diminished cytokine release, but that this treatment induced increased cytokine release in macrophages. Furthermore, we observed increased cytokine production in mouse models of pneumococcal pneumonia and tuberculosis accompanied by severely reduced bacterial clearance. This apparent inefficacy of p38 MAPK inhibition in reducing cytokine release in infectious disease, as well as its immune-compromising action, suggest that targeting p38 MAPK may not be a suitable anti-cytokine strategy in patients with such disease or at risk for infection.
Homing of In Vitro-Generated Donor Antigen-Reactive CD4+ T Lymphocytes to Renal Allografts Is α4β1 But Not αLβ2 Integrin Dependent
Authors: Hammer Markus H. , Zhai Yuan , Katori Masamichi , Ritter Thomas , Volk Hans-Dieter , Coito Ana J. , Kupiec-Weglinski Jerzy W. 
Published: April 2014

Abstract
The extravasation and sequestration of Ag-reactive T lymphocytes into vascularized organ allografts depend on a cascade of complex interactions among circulating lymphocytes, endothelial cells, and extracellular matrix proteins. Ag-activated donor-specific CD4 T cells are major initiators and effectors in the allograft rejection response. Interfering with the intragraft homing of activated CD4 T cells may represent a novel therapeutic approach in transplant recipients. We have developed a FACS-based short-term homing assay that allows tracing in vitro-generated Ag-reactive CD4 T cells after adoptive transfer in test rat recipients. Allospecific cell lines were preincubated with anti-α4β1 or anti-αLβ2 mAb, because of enhanced expression of both integrin receptors after alloactivation. The pretreated LewisBN lymphocytes were carboxyfluorescein diacetate succinimidyl ester labeled and adoptively transferred into Lewis rat recipients of Brown Norway kidney allografts. The injection of equal numbers of PKH-26-labeled untreated cells allowed quantitative comparison of both populations in the same animal. Ex vivo treatment with anti-α4β1 mAb diminished intragraft infiltration of adoptively transferred T cells by 85% in a donor-specific fashion. In contrast, treatment with anti-αLβ2 mAb did not affect intragraft cell sequestration. Hence, blocking α4β1 integrin interactions represents a novel strategy in preventing local intragraft recruitment of Ag-reactive CD4 T cells in transplant recipients.
Cutting Edge: A Role for B Lymphocyte Stimulator in Systemic Lupus Erythematosus
Authors: Zhang Jun , Roschke Viktor , Baker Kevin P. , Wang Zheng , Alarcón Graciela S. , Fessler Barri J. , Bastian Holly , Kimberly Robert P. , Zhou Tong 
Published: April 2014

Abstract
Increased levels of B lymphocyte stimulator (BLyS) are associated with systemic autoimmunity in animal models of spontaneous autoimmune disease, and transgenic animals expressing BLyS develop typical autoimmune disease. Here, we demonstrate significant elevations of BLyS in the patients with systemic lupus erythematosus (SLE). The BLyS isolated from the sera of SLE patients had the same m.w. as the natural soluble form and was able to stimulate B cell activation in vitro. Increased BLyS in SLE patients was partially associated with higher levels of anti-dsDNA Ab of the IgG, IgM, and IgA classes, but not associated with the disease activity. Our results suggest that BLyS may be a useful marker for early activation of an autoimmune diathesis and likely plays a critical role in triggering activation of self-Ag-driven autoimmune B cells in human SLE. BLyS may provide an effective therapeutic target in systemic autoimmunity.
Genetically Modified Bone Marrow-Derived Vehicle Cells Site Specifically Deliver an Anti-Inflammatory Cytokine to Inflamed Interstitium of Obstructive Nephropathy
Authors: Yamagishi Hiroko , Yokoo Takashi , Imasawa Toshiyuki , Mitarai Tetsuya , Kawamura Tetsuya , Utsunomiya Yasunori 
Published: April 2014

Abstract
In this study, we used genetically modified bone marrow-derived CD11b+CD18+ vehicle cells to deliver IL-1 receptor antagonist (IL-1ra) for treatment of inflamed renal interstitium in an animal model of unilateral ureteral obstruction (UUO). Vehicle cells that expressed the ICAM-1 ligands, CD11b and CD18, were obtained from bone marrow cells of DBA/2j mice and adenovirally transduced with the IL-1ra gene or glucocerebrosidase (GC) gene ex vivo. In kidneys treated to develop UUO, levels of ICAM-1, IL-1β, and IL-1R expression increased within 3 days compared with contralateral untreated kidneys in the same mice. Similarly, the macrophage infiltration in the cortical interstitium increased after 3 days in UUO kidneys, but not untreated kidneys. After UUO developed, DBA/2j mice were injected i.v. with either IL-1ra+ vehicle cells (IL-1ra-treated mice) or GC+ vehicle cells (GC-treated mice) at 24 h after UUO. Six days after the injection of these vehicle cells, marked increase of CD11b+ IL-1ra+ vehicle cells was observed in the ICAM-1-positive interstitium of UUO kidneys from IL-1ra-treated mice. In contrast, no CD11b+ IL-1ra+ cells appeared in ICAM-1-negative contralateral kidneys from these mice. Furthermore, the infiltration of macrophages (p &lt; 0.001), expression of ICAM-1 (p &lt; 0.005), and presence of α-smooth muscle actin (p = 0.005) in the interstitium of UUO kidneys were significantly decreased in IL-1ra-treated mice compared with GC-treated mice. These findings suggest that IL-1 may contribute to the development of renal interstitial injury and that our method can deliver a functioning gene encoding an antiinflammatory cytokine gene specifically at that site by interacting with local adhesion molecules.
Lymphoid Chemokine B Cell-Attracting Chemokine-1 (CXCL13) Is Expressed in Germinal Center of Ectopic Lymphoid Follicles Within the Synovium of Chronic Arthritis Patients
Authors: Shi Kenrin , Hayashida Kenji , Kaneko Motoharu , Hashimoto Jun , Tomita Tetsuya , Lipsky Peter E. , Yoshikawa Hideki , Ochi Takahiro 
Published: April 2014

AbstractA unique feature in inflammatory tissue of rheumatoid arthritis (RA) is the formation of ectopic lymphoid aggregates with germinal center (GC)-like structures that can be considered to contribute to the pathogenesis of RA, because local production of the autoantibody, rheumatoid factor, is thought to be a causative factor in tissue damage. However, the factors governing the formation of GC in RA are presently unknown. To begin to address this, the expression of B cell attracting chemokine (BCA-1) (CXCL13), a potent chemoattractant of B cells, was examined in the synovium of patients with RA or with osteoarthritis (OA). Expression of BCA-1 mRNA was detected in all RA samples, but in only one of five OA samples. Lymphoid follicles were observed in four of seven RA samples and in two of eight OA samples, and in most of them BCA-1 protein was detected in GC. BCA-1 was not detected in tissues lacking lymphoid follicles. Notably, BCA-1 was detected predominantly in follicular dendritic cells in GC. CD20-positive B cells were aggregated in regions of BCA-1 expression, but not T cells or macrophages. These data suggest that BCA-1 produced by follicular dendritic cells may attract B cells and contribute to the formation of GC-like structures in chronic arthritis.