bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of Histamine in the Cytokine Network in the Lung Through H2 and H3 Receptors: Stimulation of IL-10 Production
Authors: Sirois Jocelyne , Ménard Geneviève , Moses Audric S. , Bissonnette Elyse Y. 
Published: April 2014

Abstract
Histamine, a well-known inflammatory mediator, has been implicated in various immunoregulatory effects that are poorly understood. Thus, we tested the hypothesis that histamine inhibits the release of a proinflammatory cytokine, namely TNF, by stimulating the release of an anti-inflammatory cytokine, IL-10. Alveolar macrophages (AMs) from humans, Sprague Dawley rats, and the AM cell line, NR8383, were treated with different concentrations of histamine (10−5-10−7 M) for 2 h prior to their stimulation with suboptimal concentration of LPS (1 ng/ml) for 4 h. Histamine inhibited TNF release in a dose-dependent manner. This inhibition was mimicked by H2 and H3 receptor agonists, but not by H1 receptor agonist. Furthermore, we demonstrated the expression of H3 receptor mRNA in human AMs. Interestingly, treatment of AMs with anti-IL-10, anti-PGE2, or a NO synthase inhibitor (Nω-nitro-l-arginine methyl ester) before the addition of histamine abrogated the inhibitory effect of the latter on TNF release. Histamine treatment (10−5 M) increased the release of IL-10 from unstimulated (2.2-fold) and LPS-stimulated (1.7-fold) AMs. Unstimulated AMs, NR8383, express few copies of IL-10 mRNA, as tested by quantitative PCR, but expression of IL-10 was increased by 1.5-fold with histamine treatment. Moreover, the stimulation of IL-10 release by histamine was abrogated by pretreatment with anti-PGE2 or the NO synthase inhibitor, Nω-nitro-l-arginine methyl ester. Thus, histamine increases the synthesis and release of IL-10 from AMs through PGE2 and NO production. These results suggest that histamine may play an important role in the modulation of the cytokine network.
Development and Analysis of Various Clonal Alloantigen- Dependent Cytotoxic Cell Lines from Channel Catfish
Authors: Stuge Tor B. , Wilson Melanie R. , Zhou He , Barker Katherine S. , Bengtén Eva , Chinchar Greg , Miller Norman W. , Clem L. William 
Published: April 2014

Abstract
To determine the phenotypes of cytotoxic cells in channel catfish, clonal alloantigen-dependent leukocyte lines were established from mixed leukocyte cultures. Each clone was analyzed for expression of TCR α and β genes by RT-PCR and for target cell specificity by 51Cr-release assay. Based on the above criteria, the following five different cell types were identified among the 19 clones analyzed: 1) TCR αβ+ allospecific cytotoxic cells, 2) TCR αβ+ nonspecific cytotoxic cells, 3) allospecific TCR αβ+ noncytotoxic cells, 4) TCR αβ− nonspecific cytotoxic cells, and 5) TCR αβ− allospecific cytotoxic cells. The demonstration of cloned, TCR αβ+, allospecific cytotoxic effectors provides the strongest evidence to date for the existence of cytotoxic T cells in fish.
Role of Activator Protein-1 in TCR-Mediated Regulation of the Murine fasl Promoter
Authors: Matsui Ken , Xiao Sheng , Fine Alan , Ju Shyr-Te 
Published: April 2014

Abstract
The present study demonstrates that transcription factor interactions are important in regulating the murine fasl promoter following TCR-mediated activation. We used DNase I-footprinting, EMSAs, and transient transfection assays to identify the minimal TCR signal-responsive region within the fasl promoter. This region contains the previously identified binding sites for NF-κB and Egr and the AP-1 site identified in this study. We found that TCR signaling induces AP-1 binding to this site and regulates the fasl promoter function in a fashion dependent on NF-κB binding. However, mutation in the AP-1 site alone did not show a significant effect on the promoter function. The data suggest that the minimal promoter required at least two transcription factors to function.
Dual Phase Priming by IL-3 for Leukotriene C4 Generation in Human Basophils: Difference in Characteristics Between Acute and Late Priming Effects
Authors: Miura Katsushi , MacGlashan Donald W. 
Published: April 2014

AbstractPrevious studies have suggested that enhancement of mediator release from human basophils by IL-3 occurs in at least two phases, and the current studies further characterize the signaling changes that accompany these two phases of the basophil in response to IL-3. The test stimulus for these studies was anaphylatoxin split product of C component (C5a), which does not induce leukotriene C4 release without prior IL-3 treatment. Functionally, IL-3 priming occurs after 5 min, disappears by 2 h, and returns by 18 h. In contrast, the kinetics of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK1/2) phosphorylation, induced by IL-3, do not show the second rise by 18 h. The kinetics of cPLA2 and ERK1/2 phosphorylation following stimulation with C5a are the same for cells that were not treated with IL-3 as for those treated for 18 h, i.e., a lag in phosphorylation of cPLA2 and ERK1/2 lasting 30 s before its eventual rise. Previous studies showed that a 5-min treatment with IL-3 induced little change in the C5a-induced cytosolic calcium response, while 24 h of treatment resulted in a marked and sustained cytosolic calcium elevation during the C5a-induced response. The first phase of the IL-3 priming effect (5–15 min of treatment) was unaffected by cycloheximide, while the second phase (18 h) was inhibited. These data suggest that early IL-3 priming results from preconditioning cPLA2, i.e., causing its phosphorylation, while late priming results from a qualitative change in the cytosolic calcium response.
Dominance of IL-12 Over IL-4 in γδ T Cell Differentiation Leads to Default Production of IFN-γ: Failure to Down-Regulate IL-12 Receptor β2-Chain Expression
Authors: Yin Zhinan , Zhang Dong-Hong , Welte Thomas , Bahtiyar Gul , Jung Sungsoo , Liu Lanzhen , Fu Xin-Yuan , Ray Anuradha , Craft Joe 
Published: April 2014

Abstract
γδ T cells secrete Th1- and Th2-like cytokines that help mediate innate and acquired immunity. We have addressed the mechanism whereby murine γδ T cells acquire the capacity to differentially produce such cytokines. Splenic γδ T cells could be polarized into IFN-γ- or IL-4-secreting cells in vitro; however, in contrast to CD4+ αβ T cells, γδ T cells predominantly produced IFN-γ, even in the presence of IL-4, a finding independent of genetic background. Like CD4+ Th1 cells, IFN-γ-producing cells expressed the IL-12 receptor β2-chain after activation in the presence of IL-12; however, unlike Th2 cells, IL-4-primed γδ T cells also expressed this receptor, even in the absence of IFN-γ and despite the presence of the transcription factor GATA-3. IL-12 also induced IL-4-primed γδ T cells to proliferate and to translocate Stat3/Stat4, indicating signaling through the IL-12 receptor. These molecular events can account for the predominant production of IFN-γ by γδ T cells in the presence of IL-12, despite the availability of IL-4. Early and predominant production of IFN-γ by γδ T cells likely is critical for the roles that these cells play in protection against intracellular pathogens and in tumor immunity.
Vigorous Allograft Rejection in the Absence of Danger
Authors: Bingaman Adam W. , Ha Jongwon , Waitze Seung-Yeun , Durham Megan M. , Cho Hong Rae , Tucker-Burden Carol , Hendrix Rose , Cowan Shannon R. , Pearson Thomas C. , Larsen Christian P. 
Published: April 2014

Abstract
Tolerance to self is a necessary attribute of the immune system. It is thought that most autoreactive T cells are deleted in the thymus during the process of negative selection. However, peripheral tolerance mechanisms also exist to prevent development of autoimmune diseases against peripheral self-Ags. It has been proposed that T cells develop tolerance to peripheral self-Ags encountered in the absence of inflammation or “danger” signals. We have used immunodeficient Rag 1−/− mice to study the response of T cells to neo-self peripheral Ags in the form of well-healed skin and vascularized cardiac allografts. In this paper we report that skin and cardiac allografts without evidence of inflammation are vigorously rejected by transferred T cells or when recipients are reconstituted with T cells at a physiologic rate by nude bone graft transplantation. These results provide new insights into the role of inflammation or “danger” in the initiation of T cell-dependent immune responses. These findings also have profound implications in organ transplantation and suggest that in the absence of central deletional tolerance, peripheral tolerance mechanisms are not sufficient to inhibit alloimmune responses even in the absence of inflammation or danger.
Induction of Diabetes in Nonobese Diabetic Mice by Th2 T Cell Clones from a TCR Transgenic Mouse
Authors: Poulin Michelle , Haskins Kathryn 
Published: April 2014

Abstract
We have produced a panel of cloned T cell lines from the BDC-2.5 TCR transgenic (Tg) mouse that exhibit a Th2 cytokine phenotype in vitro but are highly diabetogenic in vivo. Unlike an earlier report in which T cells obtained from the Tg mouse were cultured for 1 wk under Th2-promoting conditions and were found to induce disease only in NOD.scid recipients, we found that long-term T cell clones with a fixed Th2 cytokine profile can transfer disease only to young nonobese diabetic (NOD) mice and never to NOD.scid recipients. Furthermore, the mechanism by which diabetes is transferred by a Tg Th2 T cell clone differs from that of the original CD4+ Th1 BDC-2.5 T cell clone made in this laboratory. Whereas the BDC-2.5 clone rapidly causes disease in NOD.scid recipients less than 2 wk old, the Tg Th2 T cell clones can do so only when cotransferred with other diabetogenic T cells, suggesting that the Th2 T cell requires the presence of host T cells for initiation of disease.
CD8+ T Cell-Dependent Elimination of Dendritic Cells In Vivo Limits the Induction of Antitumor Immunity
Authors: Hermans Ian F. , Ritchie David S. , Yang Jianping , Roberts Joanna M. , Ronchese Franca 
Published: April 2014

Abstract
The fate of dendritic cells (DC) after they have initiated a T cell immune response is still undefined. We have monitored the migration of DC labeled with a fluorescent tracer and injected s.c. into naive mice or into mice with an ongoing immune response. DC not loaded with Ag were detected in the draining lymph node in excess of 7 days after injection with maximum numbers detectable ∼40 h after transfer. In contrast, DC that had been loaded with an MHC class I-binding peptide disappeared from the lymph node with kinetics that parallel the known kinetics of activation of CD8+ T cells to effector function. In the presence of high numbers of specific CTL precursors, as in TCR transgenic mice, DC numbers were significantly decreased by 72 h after injection. The rate of DC disappearance was extremely rapid and efficient in recently immunized mice and was slower in “memory” mice in which memory CD8+ cells needed to reacquire effector function before mediating DC elimination. We also show that CTL-mediated clearance of Ag-loaded DC has a notable effect on immune responses in vivo. Ag-specific CD8+ T cells failed to divide in response to Ag presented on a DC if the DC were targets of a pre-existing CTL response. The induction of antitumor immunity by tumor Ag-loaded DC was also impaired. Therefore, CTL-mediated clearance of Ag-loaded DC may serve as a negative feedback mechanism to limit the activity of DC within the lymph node.
Systematic Analysis of the Role of CD19 Cytoplasmic Tyrosines in Enhancement of Activation in Daudi Human B Cells: Clustering of Phospholipase C and Vav and of Grb2 and Sos with Different CD19 Tyrosines
Authors: Brooks Stephen R. , Li Xiaoli , Volanakis Emmanuel J. , Carter Robert H. 
Published: April 2014

AbstractCD19 is a coreceptor on B cells that enhances the increase in cytoplasmic calcium and ERK2 activation when coligated with the B cell Ag receptor. Constructs containing point mutations and truncations were expressed in Daudi human B lymphoblastoid cells to systematically determine the requirement for individual CD19 cytoplasmic tyrosines in these responses. Evidence for activity was found for Y330, Y360, and Y421 as well as that previously published for Y391. Precipitates formed with phosphopeptides consisting of CD19 sequences flanking these residues were used to screen for cytoplasmic proteins that mediate signaling. Phosphopeptide Y330 precipitated Grb2 and Sos, whereas phosphopeptides Y391 and Y421 both precipitated Vav and phospholipase C-γ2. These molecules also were found associated with native CD19. In mapping studies with altered constructs, CD19 Y330 and/or Y360 were necessary for binding Grb2 and Sos. Vav associated with CD19 constitutively in unstimulated cells by a tyrosine-independent mechanism requiring the portion of CD19 encoded by exons 9–12. After B cell Ag receptor stimulation, Vav association was tyrosine-dependent, but binding was influenced by multiple residues. However, when maximally phosphorylated by pervanadate, Y391 and, to a lesser extent, Y421 were sufficient. CD19 Y391 was also both necessary and sufficient for binding phospholipase C-γ2. Thus, different tyrosines along the CD19 cytoplasmic domain provide scaffolding for the formation of complexes of different signaling molecules.
Description of an Ectothermic TCR Coreceptor, CD8α, in Rainbow Trout
Authors: Hansen John D. , Strassburger Pamela 
Published: April 2014

AbstractWe have cloned the first CD8α gene from an ectothermic source using a degenerate primer for Ig superfamily V domains. Similar to homologues in higher vertebrates, the rainbow trout CD8α gene encodes a 204-aa mature protein composed of two extracellular domains including an Ig superfamily V domain and hinge region. Differing from mammalian CD8α V domains, lower vertebrate (trout and chicken) sequences do not contain the extra cysteine residue (C strand) involved in the abnormal intrachain disulfide bridging within the CD8α V domain of mice and rats. The trout membrane proximal hinge region contains the two essential cysteine residues involved in CD8 dimerization (αα or αβ) and threonine, serine, and proline residues which may be involved in multiple O-linked glycosylation events. Although the transmembrane region is well conserved in all CD8α sequences analyzed to date, the putative trout cytoplasmic region differs and, in fact, lacks the consensus p56lck motif common to other CD8α sequences. We then determined that the trout CD8α genomic structure is similar to that of humans (six exons) but differs from that of mice (five exons). Additionally, Northern blotting and RT-PCR demonstrate that trout CD8α is expressed at high levels within the thymus and at weaker levels in the spleen, kidney, intestine, and peripheral blood leukocytes. Finally, we show that trout CD8α can be expressed on the surface of cells via transfection. Together, our results demonstrate that the basic structure and expression of CD8α has been maintained for more than 400 million years of evolution.
NKT Cells in the Rat: Organ-Specific Distribution of NK T Cells Expressing Distinct Vα14 Chains
Authors: Matsuura Akihiro , Kinebuchi Miyuki , Chen Hong-Zhi , Katabami Shigeo , Shimizu Tadakazu , Hashimoto Yuji , Kikuchi Kokichi , Sato Noriyuki 
Published: April 2014

Abstract
Rat invariant TCR α-chains and NKT cells were investigated to clarify whether CD1d-mediated recognition by NKT cells is conserved further in evolution. Rats had multiple-copies of TRAV14 genes, which can be categorized into two types according to the diversity accumulated in the CDR2 region. Rats retained invariant TCRα forms with the homogeneous junctional region similar to mouse invariant TRAV14-J281. The proportion of invariant TCR among Vα14+ clones was 12.9% in the thymus and increased in the periphery, 31% in the spleen and 95% in hepatic sinusoidal cells. The invariant TRAV14-J281 was expressed by liver sinusoidal and splenic NKT cells with CD8, CD44high, and TCR Vβ8. Type 1 invariant TCRα was expressed more frequently in hepatic lymphocytes, while type 2 invariant TCRα was expressed predominantly in the spleen. Both types of cells cytolyzed to and were stimulated to proliferate by CD1d-expressing cells in a CD1d-restricted manner. These results suggested that rat NKT cells bearing distinct Vα14 chains are distributed in a tissue-specific pattern. NKT cell populations in rats were more variable than those in mice, indicating that they play novel roles in nature. The implication of the molecular interaction between the structurally diverse invariant TCRα and CD1d/ligand complex in different organs is discussed.
HLA-DR Restricted Peptide Candidates for Bee Venom Immunotherapy
Authors: Texier Catherine , Pouvelle Sandra , Busson Marc , Hervé Mireille , Charron Dominique , Ménez André , Maillère Bernard 
Published: April 2014

Abstract
T cell epitopes containing peptides have been recently proposed as an alternative to conventional immunotherapy of allergic diseases because they are expected to be better tolerated than allergen extracts. A principal limitation to their clinical use is that they present an important diversity, which primarily results from the polymorphism of HLA class II molecules. In Caucasian populations, however, seven alleles of the most expressed molecules (namely DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, DRB1*1101, DRB1*1301, and DRB1*1501) predominate. Peptides from allergens that would efficiently bind to them should be potential candidates for specific immunotherapy. In this paper, we have determined the peptides present in the major bee venom allergen by investigating the capacity of synthetic peptides that encompass its whole sequence to bind to each allele. Several efficient binders have been identified and are either allele-specific or common to several HLA-DR molecules. Interestingly enough, the 81–97 sequence is universal in the sense that it binds to all studied molecules. This sequence is surrounded by several active regions, which make the 76–106 sequence particularly rich of binding determinants and a good candidate for specific immunotherapy. Statistical analyses of the binding data also provide an overview of the preponderant HLA-DR alleles specificity.
Unprecedented Polymorphism of Mhc-DRB Region Configurations in Rhesus Macaques
Authors: Doxiadis Gaby G. M. , Otting Nel , de Groot Natasja G. , Noort Riet , Bontrop Ronald E. 
Published: April 2014

Abstract
The rhesus macaque is an important model in preclinical transplantation research and for the study of chronic and infectious diseases, and so extensive knowledge of its MHC (MhcMamu) is needed. Nucleotide sequencing of exon 2 allowed the detection of 68 Mamu-DRB alleles. Although most alleles belong to loci/lineages that have human equivalents, identical Mhc-DRB alleles are not shared between humans and rhesus macaques. The number of -DRB genes present per haplotype can vary from two to seven in the rhesus macaque, whereas it ranges from one to four in humans. Within a panel of 210 rhesus macaques, 24 Mamu-DRB region configurations can be distinguished differing in the number and composition of loci. None of the Mamu-DRB region configurations has been described for any other species, and only one of them displays major allelic variation giving rise to a total of 33 Mamu-DRB haplotypes. In the human population, only five HLA-DRB region configurations were defined, which in contrast to the rhesus macaque exhibit extensive allelic polymorphism. In comparison with humans, the unprecedented polymorphism of the Mamu-DRB region configurations may reflect an alternative strategy of this primate species to cope with pathogens. Because of the Mamu-DRB diversity, nonhuman primate colonies used for immunological research should be thoroughly typed to facilitate proper interpretation of results. This approach will minimize as well the number of animals necessary to conduct experiments.
TGF-β2 Reduces Demyelination, Virus Antigen Expression, and Macrophage Recruitment in a Viral Model of Multiple Sclerosis
Authors: Drescher Kristen M. , Murray Paul D. , Lin Xiaoqi , Carlino Joseph A. , Rodriguez Moses 
Published: April 2014

Abstract
TGF-β2 is a potent immunoregulatory mediator that influences B cell, T cell, and macrophage function. To test whether this cytokine alters pathology in a model of virus-induced demyelinating disease, we treated SJL/J mice with TGF-β2 either before or after infection with Theiler’s murine encephalomyelitis virus. Treatment continued three times weekly through day 35 postinfection. TGF-β2 administration resulted in significantly smaller lesions and fewer virus Ag-positive cells in the spinal cords of infected SJL/J mice. Mice treated with TGF-β2 had similar levels of virus-specific IgG as infected, control-treated mice. TGF-β2 administration significantly increased the level of non-virus-specific activated CTLs, but had no effect on virus-specific CTLs. TUNEL revealed a decrease in the number of apoptotic nuclei in the spinal cord white matter of mice treated in vivo with TGF-β2. Immunostaining with an Ab to F4/80 revealed that TGF-β2-treated mice had significantly fewer F4/80-positive cells in the white matter of the spinal cord as compared with infected control-treated mice. These data suggest that TGF-β2 may control virus-induced demyelination via an immunomodulatory mechanism that reduces macrophage infiltration.
Blockade of CD14 Increases Shigella-Mediated Invasion and Tissue Destruction
Authors: Wennerås Christine , Ave Patrick , Huerre Michel , Arondel Josette , Ulevitch Richard J. , Mathison John C. , Sansonetti Philippe 
Published: April 2014

Abstract
Shigella is a diarrheal pathogen that causes disease through invasion of the large intestinal mucosa. The endotoxin of the invading bacterium may play a key role in the disease process by causing inflammation and tissue injury during infection. Earlier studies have shown that various animal species lacking functional CD14 were protected against endotoxin-mediated shock. Rabbits experimentally infected with Shigella were used to test the hypothesis that blockade of endotoxin-induced cell activation with anti-CD14 mAb would diminish inflammation and thus disease severity. Unexpectedly, we observed that the intestinal mucosa of anti-CD14-treated animals exhibited a 50-fold increase in bacterial invasion and more severe tissue injury compared with controls. Despite higher bacterial loads in treated animals, the numbers of polymorphonuclear leukocytes that were recruited to the infection site were similar to those in controls. Furthermore, the phagocytic cells of CD14-blocked animals produced IL-1 and TNF-α. Moreover, in vitro blockade of CD14 did not impede bactericidal activity. Thus, anti-CD14 treatment interfered with host defense mechanisms involved with removal/eradication of Shigella.