bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low‐level infection with Trichuris muris significantly affects the polarization of the CD4 response
Authors: Bancroft Allison J. , Else Kathryn J. , Grencis Richard K. 
Published: March 2007

AbstractResistance and susceptibility to the intestinal nematode Trichuris muris has been shown to be dependent upon the induction of T helper type 2 (Th2) or Th1 cells, respectively. This study demonstrates that in a normally resistant strain of mouse, i.e. BALB/K which mounts a dominant Th2 response, sub‐threshold levels of infection (< 40 eggs) can survive and become sexually mature adult worms (10–20 adults). The immunological basis of this phenomenon was found to be a dramatically altered polarization of the CD4 response. The Th2‐response characteristic of this strain of mouse infected with T. muris was shown to be significantly down‐regulated as assessed by in vitro cytokine production [interleukin (IL)‐4, IL‐5 and IL‐9]. In contrast, Th1 parameters of infection such as in vitro interferon‐γ production and the presence of parasite‐specific IgG2a were greatly up‐regulated in these mice.
Involvement of a serine protease in the synthesis of platelet‐activating factor by endothelial cells stimulated by tumor necrosis factor‐α or interleukin‐1α
Authors: Bussolino Federico , Arese Marco , Silvestro Lugi , Soldi Raffaella , Benfenati Emilio , Sanavio Fiorella , Aglietta Massimo , Bosia Amalia , Camussi Giovanni 
Published: March 2007

AbstractIt has been shown that production of platelet‐activating factor PAF, 1‐O‐alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine) by endothelial cells (EC) stimulated with tumor necrosis factor (TNF)‐α and interleukin (IL)‐1α requires the synthesis of new proteins and is regulated by anti‐proteinases. Here, we demonstrate that TNF‐α and IL‐1α induce the expression by EC of a 34‐kDa diisopropyl fluorophosphate‐binding protein immunoprecipitated by an antihuman elastase antibody. This protein is released in the medium and cleaves the chromogenic substrate N‐methoxysuccinyl‐ Ala‐Ala‐Pro‐Val p‐anilide, which is specific for elastase. The generation of this elastase‐like protein seems to be important for the synthesis of PAF induced by TNF‐α and IL‐lα, as suggested by the following observations: (a) it precedes the synthesis of PAF; (b) the inhibitors of serine protease and anti‐human elastase antibody prevent the synthesis of PAF and the activation of 1‐O‐alkyl‐2‐lyso‐glycerophosphocholine acetyl‐CoA: acetyltransferase, which is a key enzyme of the PAF remodelling pathway; (c) elastase, at concentrations similar to that detectable in the medium of cytokine‐activated EC, elicits a rapid synthesis of PAF by EC. High‐performance liquid chromatography‐tandem mass spectrometric analysis of bioactive PAF demonstrates that the molecular species produced after stimulation of EC with TNF‐α, IL‐1α or elastase are similar, with a predominant synthesis of the alkyl species. These results indicate that TNF‐α and IL‐1α stimulate the production of a serine protease which is critical in the activation of enzymes involved in PAF synthesis, suggesting the potential involvement of this mechanism in the regulation of EC functions.
Freshly isolated mouse 4F7+ splenic dendritic cells process and present exogenous antigens to T cells
Authors: Mohamadzadeh Mansour , Pavlidou Anastassia , Enk Alexander , Knop Jürgen , Rüde Erwin , Gradehandt Gernot 
Published: March 2007

AbstractThe antibody 4F7 was reported to recognize an epitope expressed on dendritic cells (DC) from various tissues. To study the ability of splenic 4F7+ dendritic cells to process antigen for presentation to CD4+ T cells, DC were enriched using a separation procedure avoiding overnight culture which could lead to an altered phenotype. These DC were used as antigen‐presenting cells (APC) in stimulation cultures of major histocompatibility complex class II‐restricted T cells. It was found that they induce antigen‐dependent lymphokine production by T cells and therefore could present exogenous antigens. These processing takes place intracellularly, because fixation abrogates presentation to T cells. Moreover, antigen presentation needs intracellular processing within endo‐ or lysosomes as chloroquine‐treatment prevents T cell activation. Titration of APC numbers revealed that contaminating APC most likely did not account for antigen‐specific T cell activation by DC. No evidence was found for release of antigenic peptides or for partial antigen processing possibly done by cell surface located enzymes on DC. In conclusion, these results indicate that freshly enriched DC are able to process antigens similarly to other APC.
α2,3‐Sialyl and α1,3‐fucosyltransferase‐dependent synthesis of sialyl Lewis x, an essential oligosaccharide present on L‐selectin counterreceptors, in cultured endothelial cells
Authors: Majuri Marja‐Leena , Pinola Mari , Niemelä Ritva , Tiisala Sinikka , Natunen Jari , Renkonen Ossi , Renkonen Risto 
Published: March 2007

AbstractSialyl Lewis x (sLex) oligosaccharides have been shown to be present in counterreceptors for L‐selectin. We and others have previously shown that high endothelial cells in lymph nodes and at sites of inflammation express sLex. Here we show that also cultured human umbilical vein endothelial cells (HUVEC) express sLex on their cell surface. This oligosaccharide is formed by sequential action of α2,3‐sialyl‐ (α2,3‐ST) and α1,3‐fucosyltransferases (α1,3‐FT) on N‐acetyllactosamine. At least two of the several α2,3‐ST and four of the several α1,3‐FT are present in HUVEC. In functional assays both α2,3‐ST and α1,3‐FT activities were observed in HUVEC lysates with exogenous lactosamine and sialyllactosamine acceptors, leading to the generation of the sialyllactosamine and sLex sequences, respectively. TNF stimulation increased the level of mRNA expression of FT VI, and the α1,3‐FT activity in HUVEC. Taken together these data show that endothelial cells express sLex and that they possess mRNA as well as enzyme activities of several α2,3‐ST and α1,3‐FT necessary in the final steps of sLex synthesis. Furthermore, inflammatory cytokines such as TNF can enhance transferase activities relevant in generating putative L‐selectin counterreceptors.
Characterization of two Epstein‐Barr virus epitopes restricted by HLA‐B7
Authors: Hill Ann , Worth Austen , Elliott Tim , Rowland‐Jones Sarah , Brooks Jill , Rickinson Alan , McMichael Andrew 
Published: March 2007

AbstractWe have identified two epitopes for Epstein‐Barr virus specific cytotoxic T lymphocytes (CTL) restricted by the common allele HLA‐B7. They are EBNA 3C 881–9 (QPRAPIRPI) and EBNA 3A 379–387 (RPPIFIRRL). The epitopes conform well to the recently described motif for HLA‐B7‐binding peptides (Huckzo et al., J. Immunol. 1993. 151: 2572). Titration of the peptides in CTL assays and detergent lysate binding assays revealed that extending the peptides at either the N or C terminus did not reduce their affinity for HLA‐B7. This behavior contrasted with HLA‐B51, which binds peptides with a similar motif to B7, and has identical amino acid residues at sites expected to form the “F” pocket of the peptide‐binding groove. HLA‐B51 also bound the peptide EBNA 3C 881–9, but was unable to bind peptides extended at the C terminus.
Antigen‐processing organelles from DRB1*1101 and DRB1*1104 B cell lines display a differential degradation activity
Authors: Barbey Catherine , Watts Colin , Corradin Giampietro 
Published: March 2007

AbstractWe have developed an in vitro assay for tetanus toxin (tt) C fragment (C‐fr) degradation. Purified endosomes (abbreviated endosomes 1101 or 1104) and lysosomes (abbreviated lysosomes 1101 or 1104) from the DRB1*1101 (Gly 86) and DRB1*1104 (Val 86) B cell lines were used to degrade 125I‐labeled C‐fr in vitro. Using three distinct methods of analysis, we show that the capacity of endosomes and lysosomes to degrade the tt C‐fr or tt synthetic Y‐P30 peptide differed. Using sodium dodecylsulfate‐polyacrylamide gel electrophoresis, 125I‐labeled C‐fr degradation patterns observed either with endosomes 1101/1104 or lysosomes 1101/1104 are distinct both in terms of the number of fragments and the kinetics of generation of the fragments. These results were confirmed by high‐performance liquid chromatography analysis, where we observed that the elution profiles of the 125I‐labeled Y‐P30 peptide digested by endosomes 1101/1104 were different compared to those obtained with lysosomes 1101/1104. Furthermore, the kinetics of degradation of 125I‐labeled Y‐P30 were faster with lysosomes 1104 than with lysosomes 1101. This difference in activity of the 1101 and 1104 organelles was also found in a functional assay where we showed that the activation capacity of the P30 peptide was diminished when digested by lysosome 1104, regardless of the antigen‐presenting cell (APC) used, whereas endosomes 1101 or lysosomes 1101 modified P30 peptide in a form that discriminated between presentation by 1101 or 1104 APC. Taken together, these results suggest that the differential processing and presentation displayed by the DRB1*1101 and DRB1*1104 APC is due partly to a different enzymatic content and partly to the dimorphism at position DRβ86.
Protein kinase C is not a downstream effector of p21ras in activated T cells
Authors: Williams David H. , Woodrow Melissa , Cantrell Doreen A. , Murray Edward J. 
Published: March 2007

AbstractThe aim of this present study was to investigate the role of protein kinase C (PKC), downstream of p21ras, in activating interleukin‐2 (IL‐2) gene expression. It has been reported that PKC is an effector of p21ras in T cells. Data is presented, using the potent and selective PKC inhibitor Ro 31‐8425 and transient expression of a constitutively active ras mutant, which clearly shows that PKC is not downstream of p21ras in the induction of NF‐AT and AP‐1 transcriptional activity and in the expression of IL‐2 in human Jurkat T cells. Reporter gene experiments demonstrated that NF‐χB transcriptional activity is not affected by expression of activated p21ras. The signaling pathways involving PKC activation, calcium mobilization and ras activation combine to provide the necessary components for production of IL‐2 during T cell activation.
The influence of positive selection on RAG expression in thymocytes
Authors: Kouskoff Valérie , Vonesch Jean‐Luc , Benoist Christophe , Mathis Diane 
Published: March 2007

AbstractThe expression of recombination activating gene (RAG) products, responsible for T cell receptor (TcR) gene rearrangement, is shut off during positive selection of thymocytes. The precise stage at which this down‐regulation occurs remains somewhat controversial. We have analyzed RAG‐1 expression in thymocytes of TcR transgenic mice carried on selecting versus non‐selecting genetic backgrounds, both by in situ hybridization on thymus sections and by polymerase chain reaction amplification of RNA from sorted cells. The data from several transgenic lines indicate that RAG expression is already reduced in immature, cortical, CD4+CD8+ cells in the presence of positively selecting major histocompatibility complex molecules, although complete shut‐off is not achieved until the mature, medullary, single‐positive stage. This finding has practical and theoretical significance for studies on the mechanism of positive selection.
A cytotoxic CD40/p55 tumor necrosis factor receptor hybrid detects CD40 ligand on herpesvirus saimiri‐transformed T cells
Authors: Hess Sigrun , Kurrle Roland , Lauffer Leander , Riethmüller Gert , Engelmann Hartmut 
Published: March 2007

AbstractThe B cell activation molecule CD40 and the p55 tumor necrosis factor receptor (p55TNFR) belong to the same family of structurally conserved proteins. We constructed a chimeric receptor consisting of the CD40 extracellular and transmembrane domains and the p55TNFR intracellular domain. This receptor hybrid retained the biological activity and the ligand specificity of the respective wild‐type receptor domains. Thus it exerted a marked cytotoxic effect in three different transfected cell lines after activation not only with anti‐CD40 antibody but also with CD40 ligand (CD40L) in soluble and membrane‐bound forms. Using hybrid‐transfected baby hamster kidney cells we demonstrated that herpesvirus saimiri‐transformed human CD4+ T lymphocytes constitutively express bioactive CD40 ligand on their surface. The hybrid receptor‐based assay was highly specific for CD40 activating reagents and more sensitive than an assay measuring CD40‐mediated B cell rescue from apoptosis. Hence CD40/p55TNFR transfectants may be useful for dissecting CD40L‐mediated events in T‐B cell interactions, and also to detect a defective CD40L molecule in putative hyper‐IgM syndrome patients.
Host intestinal intraepithelial γδ T lymphocytes present during acute graft‐versus‐host disease in mice may contribute to the development of enteropathy
Authors: Sakai Tetsu , Ohara‐Inagaki Kyoko , Tsuzuki Toyonori , Yoshikai Yasunobu 
Published: March 2007

AbstractWe reported that T cell receptor (TcR) γδ intestinal intraepithelial lymphocytes (i‐IEL) of host origin increased transiently, then decreased drastically at the early stage of non‐irradiated acute graft‐versus‐host disease (GVHD) in mice. We investigated the role of the TcR γδ i‐IEL of host origin in the pathogenesis of the intestinal lesions that occur during acute GVHD. The acute GVHD was induced in mice which had been depleted of TcR γδ by in vivo administration of hamster monoclonal antibody (mAb) against TcR γδ. Although the degree of splenomegaly after the induction of acute GVHD in mice treated with anti‐TcR γδ mAb was similar to that in control mice treated with hamster anti‐2,4,6‐trinitrophenyl mAb, infiltration of donor‐derived T cells into the epithelium, and mitosis and apoptosis of crypt cells in the intestinal mucosa were dramatically suppressed in these mice. This suggest that host TcR γδ T cells in i‐IEL contribute to the development of enteropathy in acute GVHD in mice.
Clearance of Sendai virus by CD8+ T cells requires direct targeting to virus‐infected epithelium
Authors: Hou Sam , Doherty Peter C. 
Published: March 2007

AbstractMinimal numbers of CD8+ T cells are found in bronchoalveolar lavage (BAL) populations recovered from Sendai virus‐infected mice that are homozygous (−/−) for β2‐microglobulin (β2‐m) gene disruption. The prevalence of the CD8+ set was substantially increased in the pneumonic lungs of 8−12‐week radiation chimeras made using substantially class I major histocompatibility complex (MHC) glycoprotein‐negative β2‐m (−/−) recipients and normal β2‐m (+/+) bone marrow. Even so, the CD8+ (but not the CD4+) lymphocyte counts were still much lower than in the (+/+)→(+/+) controls. The (+/+)→(+/+) and (+/+)→(−/−) chimeras cleared Sendai virus and potent virus‐immune CD8+ cytotoxic T lymphocytes (CTL) specific for H‐2Kb + viral nucleoprotein peptide were found in the BAL from both groups. However, following in vivo depletion of the CD4+ population, only the (+/+)→(+/+) mice were able to deal with the infection. Similarly, adoptively transferred, H‐2Kb‐restricted CD8+ T cells from previously‐primed (+/+) mice also failed to clear virus from the lungs of (+/+)→(−/−) chimeras infected within 2 weeks of reconstitution with bone marrow, though they were effective in the (+/+)→(+/+) controls. Sendai virus‐immune CD8+ T cells are thus unable to eliminate virus‐infected β2‐m (−/−) lung epithelial cells that might be thought to be expressing very small amounts of either isolated class I heavy chain, or class I MHC glycoprotein that has bound β2‐m derived from β2‐m (+/+) T cells or macrophages present in the pneumonic lung. Furthermore, the CD8+ CTL that are being exposed to β2‐m (+/+) stimulators in the BAL population cannot operate in some bystander mode to clear virus from respiratory epithelium.
Co‐Iigation of ICAM‐1 (CD54) and membrane IgM negatively affects B cell receptor signaling
Authors: van Horssen Martin , Loman Stoffer , Rijkers Ger T. , Boom Saskia E. , Bloem Andries C. 
Published: March 2007

AbstractA possible role of intercellular adhesion molecule 1 (ICAM‐1, CD54) in transmembrane signaling was investigated in B cells from the Burkitt lymphoma cell line MTLM4. Cross‐linking of membrane IgM (mIgM) induced an increase in intracellular free Ca2+ as a result of the release from intracellular stores and an influx of extracellular Ca2+. When the B cells were incubated with limiting concentrations of anti‐IgM, co‐ligation of mIgM and CD54, but not CD19, resulted in an inhibition of the Ca2+ response. Separate cross‐linking of mIgM and CD54 under these conditions, using isotype mismatched monoclonal antibodies (mAb), did not affect the mobilization of Ca2+. The CD54‐mediated inhibition of the Ca2+ response was also observed in the absence of extracellular Ca2+. All CD54 mAb tested (F10.2, F10.3 and F7.11) interfered with mIgM signaling. The results presented in this report imply that CD54 is linked to intracellular signaling pathways and, via co‐ligation with mIgM, interferes in the release of Ca2+ from intracellular stores.
Hydrogen peroxide as a potent activator of T lymphocyte functions
Authors: Los Marek , Dröge Wulf , Stricker Kirstin , Baeuerle Patrick A. , Schulze‐Osthoff Klaus 
Published: March 2007

AbstractDuring inflammatory processes infiltrating cells produce large amounts of reactive oxygen intermediates (ROI). Increasing evidence suggests that ROI besides being cytotoxic may act as important mediators influencing various cellular and immunological processes. In this study, we have investigated the effects of hydrogen peroxide on several aspects of lymphocyte activation. In ESb‐L T lymphoma cells, micromolar concentrations of hydrogen peroxide rapidly induced activation of the transcription factor NF‐χB, whereas DNA‐binding activity of the transcription factor AP‐1 was virtually not affected. In addition, hydrogen peroxide induced early gene expression of interleukin‐2 (IL‐2) and the IL‐2 receptor α chain. The stimulation of IL‐2 expression was found to be conferred by a χB‐like cis‐regulatory region within the IL‐2 gene promoter. In contrast to these activating effects, addition of hydrogen peroxide was largely inhibitory on cell proliferation which is consistent with a general requirement of thiol compounds for lymphocyte proliferation. However, hydrogen peroxide significantly increased T cell proliferation when applied for a short period under reducing conditions. These data indicate that ROI may act as an important competence signal in T lymphocytes inducing early gene expression as well as cell proliferation.
Differential reactivity of residual CD8+ T lymphocytes in TAP1 and β2‐microglobulin mutant mice
Authors: Ljunggren Hans‐Gustaf , van Kaer Luc , Ashton‐Rickardt Philip G. , Tonegawa Susumu , Ploegh Hidde L. 
Published: March 2007

AbstractTAP1 ‐/‐ and β2‐microglobulin (β2m) ‐/‐ mice (H‐2b background) express very low levels of major histocompatibility complex (MHC) class I molecules on the cell surface. Consequently these mice have low numbers of mature CD8+ T lymphocytes. However, TAP1 ‐/‐ mice have significantly higher numbers of CD8+ T cells than β2m ‐/‐ mice. Alloreactive CD8+ cytotoxic T lymphocyte (CTL) responses were also stronger in TAP1 ‐/‐ mice than in β2m ‐/‐ mice. Alloreactive CTL generated in TAP1 ‐/‐ and β2m ‐/‐ mice cross‐react with H‐2b‐expressing cells. Surprisingly, such cross‐reactivity was stronger with alloreactive CTL from β2m ‐/‐ mice than with similar cells from TAP1 ‐/‐ mice. The β2m ‐/‐ mice also responded more strongly when primed with and tested against cells expressing normal levels of H‐2b MHC class I molecules. Such H‐2b‐reactive CD8+ CTL from β2m ‐/‐ mice but not from TAP1 ‐/‐ mice also reacted with TAP1 ‐/‐ and TAP2‐deficient RMA‐S cells. In contrast, H‐2b‐reactive CD8+ CTL from neither β2m ‐/‐ mice nor TAP1 ‐/‐ mice killed β2m ‐/‐ cells. In line with these results, β2m ‐/‐ mice also responded when primed and tested against TAP1 ‐/‐ cells. We conclude that the reactivity of residual CD8+ T cells differs between TAP1 ‐/‐ and β2m ‐/‐ mice. The MHC class I‐deficient phenotype of TAP1 ‐/‐ and β2m ‐/‐ mice is not equivalent: class I expression differs between the two mouse lines with regard to quality as well as quantity. We propose that the differences observed in numbers of CD8+ T cells, their ability to react with alloantigens and their cross‐reactivity with normal H‐2b class I are caused by differences in the expression of MHC class I ligands on selecting cells in the thymus.
Biphasic control of nuclear factor‐χB activation by the T cell receptor complex: role of tumor necrosis factor α
Authors: Pimentel‐Muiños Felipe X. , Mazana Javier , Fresno Manuel 
Published: March 2007

AbstractThe regulation of nuclear factor (NF)‐χB activation by the T cell receptor (TcR)/CD3 complex in primary human T cells has been studied at various times after activation. Only p50 NF‐χB protein bound the χB element of interleukin‐2 receptor (IL‐2R) α chain promoter on resting T cells. However, immediately after TcR/CD3 cross‐linking (after approximately 1 h; immediate) binding of p50.p65 heterodimers was observed. p50.c‐rel heterodimers were also detected bound to this sequence at early time points (7–16 h; early), and both remained active at later time points (40 h; late) after activation. This regulation takes place mainly at the level of nuclear translocation of p65 and c‐rel, at immediate and early time points. Activation also induced c‐rel and p105/p50 mRNA synthesis, but not p65 mRNA whose expression was constitutive. Interestingly, all those early and late events, but not the immediate ones, were inhibited by a neutralizing anti‐tumor necrosis factor α (TNF‐α) monoclonal antibody. Similarly, cycloheximide prevented the p65 and c‐rel translocation and consequent formation of active binding heterodimers, at early and late times. Cyclosporin A impaired not only early and late, but also immediate events; however, addition of TNF‐α prevented all inhibition. These results indicate that the regulation of NF‐χB activation during T cell activation by TcR/CD3 signals is biphasic: TcR/CD3 triggers its immediate translocation, which is transient if no TNF‐α is present. TNF‐α, therefore, emerges as the main factor responsible for a second phase of NF‐χB regulation, controlling both translocation of p65 and c‐rel, and new mRNA synthesis for c‐rel and p105/p50.
Isotype exclusion in λ1 transgenic mice depends on transgene copy number and diminishes with down‐regulation of transgene transcripts
Authors: Hengstschläger Markus , Maizels Nancy 
Published: March 2007

AbstractWe have compared expression of the endogenous χ and transgenic λ1 light chains in three lines of mice carrying one, four and eight copies of a λ1 transgene. We have found that in very young mice, even a single rearranged transgenic λ allele excludes expression of the endogenous χ loci. As the λ1 transgenic mice age, the proportion of λ‐positive cells decreases, as has been reported by others (Neuberger et al., Nature 1989. 338: 350; Pettersson et al., Nature 1990. 344: 165; Hagman et al., J. Exp. Med. 1989. 169: 1911; Bogen and Weiss, Eur. J. Immunol. 1991. 21: 2391). The decrease in λ‐positive B cells is accompanied by an increase in χ‐positive cells. We show that the decrease in B cells bearing surface λ immunoglobulin depends on transgene copy number and occurs most rapidly in lower copy number lines. The decrease in surface λ expression correlates with a dramatic decrease in the level of λ mRNA in splenic B cells. Transgene down‐regulation cannot be alleviated by stimulation of splenocytes with the mitogen lipopolysaccharide. These are the first data to establish that a single copy transgene can effect isotype exclusion. In addition, these results provide strong evidence that down‐regulation of transgene expression is controlled at the level of transcription, and that it is the level of expressed light chain that regulates isotype exclusion.