bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA class I and II molecules present influenza virus antigens with different kinetics
Authors: Kuijpers Karel C. , Van Kemenade Folkert J. , Hooibrink Berend , Neefjes Jacques J. , Lucas Cees J. , Van Lier René A. W. , Miedema Frank 
Published: March 2007

AbstractHuman leukocyte antigen (HLA) class I and class II molecules differ with respect to their intracellular pathways and the compartments where they associate with processed antigen. To study possible consequences of these differences for the kinetics of antigen presentation by HLA class I and class II molecules, we analyzed changes in the concentrations of free intracellular calcium ions in influenza virus‐specific T cell clones after recognition of specific antigen/HLA complexes. HLA class II‐restricted viral antigen presentation by Epstein‐Barr virus‐transformed B lymphoblastoid cell lines (B‐LCL) to CD4+ T cell clones started within 1 h and showed little variability, irrespective of antigen specificity or restriction element tested. In contrast, kinetics of viral antigen presentation by HLA class I molecules to CD8+ T cell clones were slower and differed for three antigen/HLA class I complexes tested. While B‐LCL presented antigen by HLA‐A2 and by HLA‐B37 after at least 2 h, they only started to present antigen in the context of HLA‐B7 after more than 4 h. This difference in kinetics did not correlate with differences in bulk transport rates of HLA‐A2, HLA‐B37, and HLA‐B7, but seemed greatly influenced by differential rates of peptide generation. Brefeldin A treatment of B‐LCL showed for both HLA class I and class II that de novo synthesized HLA molecules were involved in antigen presentation. Thus, differences between intracellular pathways of HLA class I and class II molecules may result in different kinetics of antigen presentation.
Inhibition of human immunodeficiency virus infection in human colon epithelial cells by recombinant interferon‐γ
Authors: Yahi Nouara , Baghdiguian Stephen , Bolmont Christine , Fantini Jacques 
Published: March 2007

AbstractPretreatment of human colon epithelial cells HT29 by recombinant gamma interferon (IFN)‐γ was found to protect the cells from infection with various isolates of human immunodeficiency virus (HIV)‐1 and HIV‐2, as assessed by co‐cultivation with human T lymphoblastoid cells and gene amplification by polymerase chain reaction technique. Additionally, IFN‐γ induced a dose‐dependent inhibition of HIV‐1 and HIV‐2 production in chronically infected HT29 cells. In situ hybridization studies demonstrated that IFN‐treated cells were still able to synthesize viral messenger ribonucleic acid. However, the expression of the p24 product of the gag gene was markedly decreased after IFN treatment as demonstrated by radio‐immunoprecipitation assay. Taken together, these data suggested that the cytokine acted at the post‐translationnal level by inhibiting the processing of structural viral proteins. It is concluded from this study that IFN‐γ has a potent anti‐HIV effect on epithelial gastrointestinal cells.
Modulation of restricted class II T cell responses by peptides derived from self class II molecule
Authors: Li Wan‐Fen , Fan Ming‐Dau , Pan Ching‐Biau , Gefter M. L. , Lai Ming‐Zong 
Published: March 2007

AbstractWe have explored the possibility of using peptides derived from a major histocompatibility complex (MHC) class II (I‐Ab) molecule to modulate I‐Ab‐restricted T cell responses. Six peptides spanning the polymorphic regions of I‐Ab were analyzed for competitive binding to the I‐Ab molecule, and for efficacies in blocking I‐Ab‐specific T cell response. Only PB1 (residues 75‐91 of β chain) bound the I‐Ab molecule with high affinity. When these MHC‐derived peptides were administered simultaneously with antigen, PB1 effectively inhibited I‐Ab‐restricted T cell responses as well as another peptide PB2 (residues 59‐78 of β chain). PB2 inhibited specific T cell response only when it was administered simultaneously with antigen. Since PB2 is a weak binder of I‐Ab, an additional mechanism must account for its inhibitory activity. Both PB1 and PB2 peptides elicited specific T cell responses, indicating that these peptides were not tolerogenic in syngeneic mice. However, the induction of T cells in response to PB1 and PB2 did not increase reactivity to I‐Ab. MHC class II‐derived peptides thus can be used to regulate T cell responses without the risk of autoreactivity.
The importance of cross‐linking in the homotypic aggregation of lymphocytes induced by anti‐leukosialin (CD43) antibodies
Authors: Cyster Jason G. , Williams Alan F. 
Published: March 2007

AbstractLeukosialin (CD43) is a major glycoprotein of T lymphocytes which has an extracellular domain of 45 nm in length that is heavily O‐glycosylated. Monoclonal antibodies (mAb) to the extracellular domain of human leukosialin induce aggregation of T lymphocytes, monocytes and some cell lines that express leukosialin. The aggregation was reported in one case to be inducible by Fab fragments. In the present study, nine mAb specific for rat leukosialin were tested as inducers of thymocyte aggregation and all were effective. The level of aggregation was reduced by metabolic and cytoskeletal inhibitors, by removal of divalent cations and by reducing the temperature from 37°C to 4°C. The aggregation produced by mAb specific for certain epitopes was less sensitive to these inhibitors than aggregation induced by mAb to other epitopes. To examine the requirement for cross‐linking, Fab fragments of four of the antibodies were tested and found to be inactive except for those derived from the OX75 mAb. However, OX75 Fab showed a tendency to dimerize, and monomeric OX75 Fab obtained directly after gel filtration was unable to induce aggregation. Thus induction of rat thymocyte aggregation by anti‐leukosialin antibodies requires bivalent cross‐linking and maximal aggregation is dependent on energy and an, intact cytoskeleton. Mechanisms of antibody‐induced aggregation are considered and it is proposed that in the case of leukosialin the antibodies may cross‐link cells to overcome inherent repulsion between them and that subsequently other adhesion molecules complete the clustering process.
Activated human T cells express a ligand for the human B cell‐associated antigen CD40 which participates in T cell‐dependent activation of B lymphocytes
Authors: Lane Peter , Traunecker André , Hubele Sabine , Inui Seiji , Lanzavecchia Antonio , Gray David 
Published: March 2007

AbstractTo identify the ligand for the B cell‐associated antigen CD40, we constructed a chimeric immunoglobulin molecule where the extracellular portion of the CD40 protein replaced the normal immunoglobulin variable region. No binding was detected on resting peripheral blood T cells. However, following T cell activation with phorbol esters and ionomycin, the chimeric protein bound specifically to activated human T cells and precipitated a 35‐kDa protein from such cells. The induction of the CD40 ligand was detectable on the cell surface after 1 h, with maximal expression after 8 h of stimulation. The T cells expressing CD40 ligand were predominantly CD4 positive, although a proportion of CD8‐positive cells also expressed the protein. There was no particular correlation with CD45 phenotype. Finally, we found that soluble CD40 inhibited T‐dependent B cell proliferation. The results are discussed in the context of cognate interactions between B and T cells.
Pore‐forming protein in individual cytotoxic T lymphocytes: the effect of senescence provides a probe for understanding the lytic mechanism
Authors: Horvath Judith A. , Mostowski Howard S. , Okumura Ko , Bloom Eda T. 
Published: March 2007

AbstractThe senescent decline of cytolytic T lymphocyte (CTL) activity was examined (a) to learn more about the effect of aging on the immune system, and (b) to probe the mechanism of cell‐mediated cytolysis. The effect of age on the generation of pore‐forming protein (Pfp) was examined at the cellular level in a murine model using CTL stimulated in allogeneic mixed lymphocyte culture (MLC). Pfp expression was analyzed by immunocytochemistry and enzyme‐linked immunosorbent assay (ELISA). Immunocytochemical analyses of Pfp in MLC‐stimulated splenic T cells from a large number of mice revealed that although stimulated cells from aged mice exhibited fewer Pfp‐producing cells than those from young, the diminution in the proportion of Pfp+ cells was small compared to the age‐related decrease in lytic activities (∼2‐fold vs. ∼7.4‐fold, respectively). Time‐course analysis disclosed similar kinetics for the generation of Pfp+ cells among responding cells from young and aged mice. No significant age‐related difference in the proportion of Pfp+ cells was observed in MLC‐stimulated lymph node cells despite a large and significant difference in lytic activity (∼ 6.5‐fold). Purified CD8+ T cells demonstrated a large age‐related difference in CTL activity (∼3–11‐fold) and accounted for virtually all the Pfp. Although little difference in the proportion of Pfp+ CD8+ T cells could be detected between age groups, stimulated CD8+ cells or whole splenic T cells from old mice consistently exhibited a striking reduction in both the intensity of Pfp staining and the apparent numbers of granules per cell. This difference in Pfp was examined by ELISA and total Pfp levels were found to be ∼ 12‐fold greater in CTL generated from splenic T cells of young compared to aged mice. The results demonstrate that Pfp levels are reduced in CTL from aged compared to young mice at the level of the individual cells and suggest the possibility that a threshold level of Pfp may be required for potency of effector cell function.
The influence of orientation and number of copies of T and B cell epitopes on the specificity and affinity of antibodies induced by chimeric peptides
Authors: Partidos Charalambos , Stanley Carolynne , Steward Michael 
Published: March 2007

AbstractCBA and TO mice were immunized with chimeric peptide immunogens consisting of B cell (residues 404–414) and T cell (residues 288–302) epitopes from the F protein of measles virus. The chimeras were co‐linearly synthesized to contain one or two copies of the T cell epitope linked to one or two copies of the B cell epitope via a glycine glycine spacer. Two orientations were synthesized such that the T cell epitope(s) were located at either the amino or carboxyl terminus of the B cell epitope(s). The levels of antibody induced following immunization with the chimeras were assessed by enzyme‐linked immunosorbent assay using microtiter plates coated with either the homologous chimera or the B cell epitope sequence. The affinities of the anti‐chimera antibodies for the B cell epitope were assessed by a fluid‐phase double‐isotope radioimmunoassay. All the chimeras induced good antibody responses in both strains of mice with specificity for the B cell epitope. Chimeras containing two copies of the T cell epitope induced antibodies with higher affinity for the B cell epitope than did chimeras containing one copy of the T cell epitope or two copies of the B cell epitope. Furthermore, the amino terminal location of the T cell epitope in relation to the B cell epitope in the chimera induced higher affinity anti‐B cell antibody than did the reverse orientation. These results suggest that orientation of epitopes and amino acid composition of chimeric peptides affect antigen processing and presentation to T cells which govern both the specificity and affinity of antibody produced. Thus, for the production of synthetic peptide immunogens with vaccine potential, attention needs to be given to the number and orientation of the component epitopes required to produce highest affinity antibody.
Predominance of Th1‐type T cells in synovial fluid of patients with Yersinia‐induced reactive arthritis
Authors: Schlaak Jörg , Hermann Elisabeth , Ringhoffer Mark , Probst Peter , Gallati Harald , zum Büschenfelde Karl‐Hermann Meyer , Fleischer Bernhard 
Published: March 2007

AbstractThe pathogenetic mechanisms underlying the development of reactive arthritis and the functional capacities of synovial T cells specific forYersinia enterocoliticaare still unclear. In this study we have determined the cytokine secretion patterns of 24 CD4+synovial fluid (SF)‐derived T cell clones from 2 patients with Yersinia‐induced reactive arthritis, 16 clones specific for different Yersinia antigens and 8 clones as controls. The clones specific for Yersinia antigens predominantly belong to the T helper cell 1 (Th1) subset with production of interferon (IFN)‐γ and interleukin (IL)‐2, but no IL‐4, whereas SF T cells not reactive with Yersinia antigens produce IL‐2, IL‐4 and IFN‐γ and thus belonged to the Th0 subset. Moreover, short‐term T cell lines established from SF and peripheral blood showed the same pattern. To further analyze the functional relevance of these data we investigated the influence of IFN‐γ and IL‐4 on the intracellular killing of Yersinia in a human glioblastoma cell line. Our data show that the Th1 cytokine IFN‐γ promotes intracellular killing of Yersinia, whereas this effect is antagonized by the Th2 cytokine IL‐4. Furthermore, the Th2 cytokine IL‐10 inhibited the antigen‐specific proliferative response and IFN‐γ and IL‐2 production by the Th1 cells. These results provide insight into the antibacterial mechanisms at work in reactive arthritis after infection withYersinia enterocoliticaand, for the first time, reveal the cross‐regulatory properties of cytokines derived from Th1 and Th2 cells in a human immune response to bacterial antigens.
Differential thymus dependence of rat CD8 isoform expression
Authors: Torres‐Nagel Nora , Kraus Elmar , Brown Marion H. , Tiefenthaler Georg , Mitnacht Rita , Williams Alan F. , Hünig Thomas 
Published: March 2007

AbstractExpression of the rat CD8 molecule was studied using five novel monoclonal antibodies (mAb), four of which are specific for the V‐like domain of CD8α, whereas one reacts either with the β chain or with a determinant only expressed on the CD8 α/β heterodimer. mAb to both chains effectively blocked purified lymph node CD8 T cells in mixed lymphocyte reaction and in cell‐mediated cytotoxicity. Flow cytometric analysis showed that CD8 T cells from lymph nodes or spleen of normal rats almost exclusively express the α/β isoform, regardless of the T cell receptor isotype (α/β or γ/δ). In contrast, natural killer (NK) cells carry only CD8α chains. This CD8α+β− phenotype was also prominent among CD8 T cells from athymic rats and from intestinal epithelium of normal rats. CD8α homodimers can also be expressed as a result of activation, as shown by analysis of CD4 CD8 double‐positive T cells obtained from highly purified lymph node CD4 T cells by in vitrok stimulation. Such CD4+CD8α+β− cells also represent a major subset among adult intestinal intraepithelial lymphocytes (IEL), suggesting local activation. Taken together, the difference in CD8 isoform expression among T cells from athymic rats, NK cells, and gut IEL versus CD8 T cells from peripheral lymphatic organs of euthymic animals suggests that like in mice, expression of the CD8 heterodimer is more dependent on intrathymic maturation than that of the homodimer. Since the more stringent thymus dependence of CD8α+β+ T cells may be due to a requirement for thymic selection on self major histocompatibility complex class I antigens, the virtually exclusive CD8α+β+ phenotype of peripheral rat γ/δ T cells could mean that antigen recognition by this subset is also restricted by MHC class I molecules.
In vivo administration of interleukin‐2 turns on anergic self‐reactive T cells and leads to autoimmune disease
Authors: Gutierrez‐Ramos José C. , De Alboran Ignacio Moreno , Martinez‐A Carlos 
Published: March 2007

AbstractOne major mechanism of self tolerance involves the deletion of T cell clones in the thymus. In athymic mice, tolerance to self antigens must be generated extrathymically. T cells with self‐reactive receptors undergo either peripheral clonal deletion or become unresponsive (i.e. anergic). The unresponsive state of human and mouse T cell clones in vitro can be reversed by the addition of exogenous interleukin (IL)‐2, thus transforming anergic T cells to an activated state. Here it is shown that the in vivo delivery of IL‐2 to athymic BALB/c nu/nu mice abrogates the anergic state of self‐reactive Vβ3+ and Vβ11+ T cells [which are normally deleted in the minor lymphocyte stimulatory (Mls)‐1b‐, I‐E+‐expressing euthymic counterparts]. Thus, Vβ3+ and Vβ11+ T cells from IL‐2‐treated nude mice proliferate in response to T cell receptor cross‐linking and acquire effector functions as measured by their ability to deliver aid to B cells upon specific stimulation. This activation correlates with the development of autoimmune manifestations (DNA autoantibodies, rheumatoid factors, erythroleukopenia and minimal change nephritis) in these IL‐2‐treated mice.
Interferon‐γ induced lethality in the late phase of Plasmodium vinckei malaria despite effective parasite clearance by chloroquine
Authors: Kremsner Peter G. , Neifer Stefan , Chaves Mair F. , Rudolph Roland , Bienzle Ulrich 
Published: March 2007

AbstractA combination therapy was tested consisting of chloroquine and interferon‐γ (IFN‐γ) in the late phase of blood‐stage Plasmodium vinckei malaria in BALB/c mice. When mice were treated with three times 300 μg chloroquine at 24‐h intervals starting at a parasitemia of 30%‐50%, only 5 of 14 mice (36%) died 2–4 days after initiation of therapy. However, when infected mice received chloroquine plus 1 μg IFN‐γ at the same time, 14 of 18 mice (78%) died 0.5–3 days after start of therapy (p < 0.05) despite clearance of parasitemia. The histopathology from mice dying after combination therapy revealed interstitial leukocyte infiltration of lung tissue, severe liver cell necrosis and kidney tubular necrosis.Pretreatment of P. vinckei‐infected mice with pentoxifylline, a phosphodiesterase inhibitor, led to a significant decrease of IFN‐γ‐induced lethality (p < 0.05). In contrast, pretreatment with neutralizing antibodies to tumor necrosis factor or with L‐N‐monomethyl arginine, the latter an inhibitor of the nitric oxide synthase, significantly increased lethality (p < 0.05).
Heat shock prevents lipopolysaccharide‐induced tumor necrosis factor‐α synthesis by rat mononuclear phagocytes
Authors: Fouqueray Bruno , Philippe Carole , Amrani Abdelaziz , Perez Joëlle , Baud Laurent 
Published: March 2007

AbstractTumor necrosis factor‐α (TNF‐α), a mononuclear phagocyte‐derived peptide is known to participate in the pathogenesis of fever. To determine whether a feedback mechanism exists by which elevated temperatures influence TNF‐α generation, we have examined the effects of heat shock on the in vitro synthesis of TNF‐α by rat glomeruli, inflammatory peritoneal macrophages and blood monocytes. Preexposure of peritoneal macrophages to elevated temperatures for 20 min decreased the subsequent lipopolysaccharide‐induced release of TNF‐α bioactivity. The mean reductions were 11.9 ± 86.3 ± 12.0, and 95.2 ± 3.5% after pretreatment at 39, 41 and 43°C, respectively. Reductions, that were transient, were maximum when lipopolysaccharide was added 0–2 h after heat shock. They correlated with the decreased release of immunoreactive TNF‐α and the decreased expression of both cell‐associated TNF‐α molecule and TNF‐α mRNA. Heat shock‐induced inhibition of TNF‐α release was independent of variations of prostaglandin synthesis, but was possibly related to the induction of heat‐shock proteins since (a) macrophages exposed to heat shock synthesized the major 70‐ and 90‐kDa heat‐shock proteins, and (b) chemical inducers of the heat‐shock response were also effective inhibitors of TNF‐α release. The mean reduction of TNF‐α release after pretreatment at 41°C was found to be identical in glomerular tissue (82.0 ± 7.5%), but significantly less in blood monocytes (43.9 ± 10.9%). This supports the hypothesis that a negative‐feedback mechanism exists between elevated temperature and lipopolysaccharide‐induced TNF‐α synthesis, and suggests that this regulation is less active in blood monocytes than in tissue macrophages.
Evidence for a role of CD28RE as a response element for distinct mitogenic T cell activation signals
Authors: Civil Azem , Geerts Marlieke , Aarden Lucien A. , Verweij Cornelis L. 
Published: March 2007

AbstractT lymphocytes can be induced to produce interleukin (IL)‐2 and proliferate upon T cell receptor (TcR) occupancy together with a CD28‐induced co‐stimulatory signal. The T cell surface molecule CD28 is believed to function as a regulator in T cell activation at both the level of lymphokine mRNA stabilization and gene transcription. Activation of IL‐2 gene transcription via CD28 has been shown to be mediated through a xB‐like sequence, called CD28RE. DNA binding analysis revealed that the CD28‐induced signal is involved in the induction of CD28RE binding activity. Here, we demonstrate that the induction of CD28RE binding activity is not specific for the CD28‐induced signal. Our data indicate that distinct mitogenic T cell activation signals converge on the induction of CD28RE binding activity, and suggest a crucial role for this activity in the IL‐2 enhancer responsiveness to different modes of T cell activation.
Polyreactive autoantibodies to negatively charged epitopes following Trypanosoma cruzi infection
Authors: Kahn Stuart , Kahn Maria , Eisen Harvey 
Published: March 2007

AbstractDuring the course of many human autoimmune diseases, antibodies which recognize negatively charged epitopes on self antigens are detected. Trypanosoma cruzi, an intracellular protozoan parasite capable of infecting a wide variety of vertebrates, is the cause of Chagas disease in humans. Infection with the parasite frequently results in autoimmune and inflammatory pathology. We report here on an affinity‐purified population of antibodies that bind to a broad class of antigens that contain runs of acidic amino acids, including tubulin. Although these antibodies can be isolated from both uninfected and T. cruzi chronically infected C3H/He mice, the antibodies from the normal mice (the natural autoantibodies) bind to tubulin poorly at physiological pH, whereas the antibodies isolated from the infected animals bind well at physiological pH. We propose that similar processes may occur in humans following other infections accounting for the detection of antibodies to negatively charged epitopes in a variety of autoimmune diseases.
Vaccination or tolerance to prevent diabetes
Authors: Oehen Stephan , Ohashi Pamela S. , Aichele Peter , Bürki Kurt , Hengartner Hans , Zinkernagel Rolf M. 
Published: March 2007

AbstractExperiments with transgenic mice expressing the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) under the control of the rat insulin promoter (RIP) have demonstrated that potentially self‐reactive T cells that normally ignore self peptides may nevertheless be induced by self peptides or “cross‐reactive” foreign (e.g. viral) peptides that arise in the host in an immunogenic form; once activated these potentially self‐reactive T cells may cause autoaggressive diseases (e.g. diabetes). The possibility of vaccinating against such T cell‐mediated immunopathological diseases was evaluated in the RIP‐GP transgenic mouse line Bln. Any attempt to vaccinate with the self antigen itself (e.g. recombinant vaccinia virus expressing LCMV‐GP) failed to protect mice from disease. However, immunization with a recombinant vaccinia virus expressing LCMV‐nucleoprotein (vacc‐NP) as a non‐GP LCMV vaccine was able to modulate the immune response and prevented autoaggressive disease in a MHC‐dependent fashion. In contrast, tolerance induction neonatally or, more generally applicable, by lethal irradiation and reconstitution with neo‐self antigen‐expressing bone marrow cells always resulted in prevention of virally induced diabetes in this model situation.