bluuebunny/crossref_metadata_2025_split huggingface dataset:
The distribution of CD10 (NEP 24.11, CALLA) in humans and mice is similar in non‐lymphoid organs but differs within the hematopoietic system: absence on murine T and B lymphoid progenitors
Authors: Kalled Susan L. , Siva Niranjan , Stein Harald , Reinherz Ellis L. 
Published: March 2007

AbstractPrior studies in the human have implied an important function for CD10 (CALLA, neutral endopeptidase 24.11) in early lymphoid development. To examine the role of this ectoenzyme in an experimental system, a rat mAb specific for mouse CD10, termed R103, was generated. Immunohistological and flow cytometric analyses indicate that the distribution of CD10 in non‐lymphoid anatomical compartments is virtually identical in human and mouse. However, CD10 expression within the hematopoietic system is strikingly different. In contrast to human spleen, lymph node and thymus, the corresponding mouse organs contain no detectable CD10+ cells. Mouse granulocytes, unlike human granulocytes, also lack CD10 expression. Five‐color flow cytometric studies of adult bone marrow (BM) from C57BL/6 and BALB/c mice with mAb specific for CD43, B220, HSA, BP‐1 and immunoglobulin M fail to detect any significant number of CD10+ cells at pro‐B, pre‐B or B cell stages. In addition, lymphoid cells in both (rIL‐7) independent and rIL‐7‐dependent in vitro pro‐B cell cultures lack CD10 expression. Consistent with this result, CD10 mRNA is not detected. Unlike the AA4.1+ population from day 13 and 14 fetal liver, the CD10+ subset is unable to reconstitute T and B lymphoid compartments in RAG‐2−/− mice. Nevertheless, mouse CD10 is readily found on BM stromal elements known to support early B lineage lymphoid development. Given the common expression of CD10 on human and mouse BM stromal elements, this enzyme may have an important function in the stromal cell‐dependent phase of hematopoiesis.
HLA‐dependent variations in human immunodeficiency virus Nef protein alter peptide/HLA binding
Authors: Couillin Isabelle , Connan Francine , Culmann‐Penciolelli Béatrice , Gomard Elisabeth , Guillet Jean‐Gérard , Choppin Jeannine 
Published: March 2007

AbstractIn human immunodeficiency virus (HIV) infection, sequence variations within defined cytotoxic T lymphocyte (CTL) epitopes may lead to escape from CTL recognition. In a previous report, we have shown that the variable central region of HIV Nef protein (amino acids 73–144) that contains potential CTL epitopes, can escape the CTL response. We suggested that this non recognition occurs through a variety of mechanisms. In particular, we provided evidence that HIV Nef sequences recovered from HLA‐A11‐expressing individuals have alterations in the major anchor residues essential for binding of the two Nef epitopes (amino acids 73–82 and 84–92) to the HLA‐A11 molecule. Here, we investigate in more detail whether variations in autologous Nef sequences affect HLA binding, leading to CTL escape. Potential epitopes were sought by testing Nef peptides containing the HLA‐A11‐specific motif or related motifs. We confirmed that only the two previously described epitopes identified in cytolysis tests have optimal reactivity with the HLA‐A11 molecule. We then sequenced several viral variants from donors that do not express the HLA‐A11 molecule and compared the variability of these epitopes with those obtained from HLA‐A11‐expressing individuals. One substitution (Leu85) found in the sequences isolated from both populations increase the reactivity of the HLA‐A11‐restricted epitope 84–92, and might explain the difference in immunogenicity observed between the two HLA‐A11‐restricted epitopes from HLA‐A11+ individuals. In addition, selective variations were only detected in virus isolated from HLA‐A11‐expressing individuals. Furthermore, examination of the association of variant peptides with the HLA‐A11 molecule demonstrated that a single substitution within the minimal epitope could not always completely abrogate HLA binding, suggesting that multiple alterations within a particular epitope may accumulate during disease progression, allowing the virus to escape CTL recognition.
Intrathymic T cell receptor (TcR) targeting in mice lacking CD4 or major histocompatibility complex (MHC) class II: Rescue of CD4 T cell lineage without co‐engagement of TcR/CD4 by MHC class II
Authors: Müller Klaus‐Peter , Kyewski Bruno A. 
Published: March 2007

AbstractA critical step during intrathymic T cell development, termed positive selection, is associated with rescue of short‐lived, immature thymocytes from programmed cell death, T cell lineage commitment, and induction of lineage‐specific differentiation programs. T cell receptor (TcR)‐major histocompatibility complex (MHC) interactions during positive selection can be closely mimicked by targeting TcR on immature thymocytes to cortical epithelial cells in situ via hybrid antibodies. Here, we show that antibody‐mediated TcR signaling in mice deficient for CD4 or MHC class II expression induces polyclonal differentiation of the CD4 T cell lineage. Following a single TcR signal pulse in situ, a temporal sequence of phenotype changes can be discerned: CD69 up‐regulation (< 1 day), CD8 down‐regulation, TcR up‐regulation (1–1.5 days) and down‐regulation of the heat‐stable antigen (1.5–2 days). Differentiation of phenotypically and functionally mature CD4 T cells in situ is attained within 3 days. Rescue of CD4 lineage T cells in the absence of TcR/CD4 co‐engagement by MHC class II in this experimental system supports the stochastic/selective model of T cell lineage commitment.
Identification of a major T cell immunogen in the anti‐schistosome response of adult residents in an area endemic for Schistosoma mansoni
Authors: Couissinierhyphen;Paris Patricia , Bourgois Alain , Dessein Helia , Bacellar Olivia , Rodrigues Virmondes , Kohlstädt Sybille , Buonavista Nathalie , Pène Jérome , Dessein Alain‐Jacques 
Published: March 2007

AbstractVaccine‐induced immunity to Schistosoma mansoni infection depends on the specific priming of certain T cell subsets and on the recall of this response by natural infections months or years after vaccine administration. Thus, those schistosome proteins that activate T cells in individuals stimulated by natural infections are potential candidate vaccine antigens. In the present study, we identified and purified one such T cell‐stimulating antigen and evaluated its immunological properties in subjects living in an area endemic for Schistosoma mansoni. Chromatography fractions (gel filtration, followed by ion exchange chromatography) of soluble extracts of schistosomula were screened for their ability to stimulate schistosome‐specific T cell clones derived from a subject sensitized by natural infection. A fraction stimulating most clones was identified and characterized. A few nanograms of this fraction, containing a major 9‐10‐kDa component, stimulated the T helper cells of most adults living in an endemic area of Brazil, and was able to trigger a strong cutaneous immediate hypersensitivity reaction. In contrast, children reacted weakly to this antigen preparation both in blastogenesis and in skin tests, although they mounted a significant reaction to crude larval antigen preparations. In conclusion, this work identifies a schistosomula antigen that induces a strong T cell response in adults sensitized by natural infections. This T cell response develops gradually in children and adolescents, is apparently not restricted by the HLA haplotypes common in the study area, and allows the production of parasite‐specific IgE antibodies. Thus, this T cell response has some features of the immune response that is believed to protect chronically exposed humans from reinfection.
Interactions between the tyrosine kinases p56lck, p59fyn and p50csk in CD4 signaling in T cells
Authors: Baldari Cosima T. , Di Somma M. Maddalena , Milia Elisabetta , Bergman Mathias , Telford John L. 
Published: March 2007

AbstractInteraction of the CD4 co‐receptor with major histocompatibility complex (MHC) class II molecules during antigen presentation results in enhancement of antigen receptor signaling. The synergism between the two receptors is believed to result from the juxtaposition of the CD4‐associated tyrosine kinase p56lck with the cytoplasmic domains of CD3 complex components. Here, we report that cross‐linking of CD4 on the surface of Jurkat cells using monoclonal antibodies results in activation of the CD3‐associated kinase p59fyn. Co‐cross‐linking of CD4 and CD3 results in synergistic activation of p59fyn. The p59fyn kinase is also hyperactive in a Jurkat cell line stably transfected with a constitutively active p56lck mutant, indicating that p56lck mediates CD4 activation of p59fyn. In support of this hypothesis, expression of a dominant inhibitory mutant of p59fyn blocks CD4 signals involved in gene activation. In addition, the p59fyn dominant inhibitor mutant blocks gene‐activating signals induced by expression of a constitutively active mutant of p56lck. Overexpression of the regulatory kinase p50csk, which attenuates TcR signaling by inactivation of p59fyn, inhibits signaling from the constitutively active form of p56lck. Taken together, these data suggest that CD4/p56lck enhancement of TcR signaling is, at least in part, mediated by activation of p59fyn, and may be regulated by p50csk.
Resistance to anti‐IgM‐induced apoptosis in a WEHI‐231 subline is due to insufficient production of ceramide
Authors: Gottschalk Alexander R. , McShan Carol L. , Kilkus John , Dawson Glyn , Quintáns Jose 
Published: March 2007

AbstractWe describe the properties of a physiological cell death (PCD)‐resistant subline of WEHI‐231 generated from the PCD‐susceptible WEHI‐231.7 JM cell line maintained in our laboratory. The PCD‐resistant WEHI‐231.7 JMRE subline was uniquely resistant to anti‐immunoglobulin (Ig)M‐induced PCD but not to irradiation and etoposide. In these sublines, we compared the expression of genes implicated in regulating PCD. Northern analysis of c‐myc, c‐fos, egr‐1, Fas, p53 and retinoblastoma revealed similar basal levels of expression in all sublines tested and comparable responses to anti‐IgM treatment. Similarly, the expression of bcl‐2, bcl‐x, bax and IL‐1β converting enzyme did not correlate with susceptibility to anti‐IgM‐induced PCD. Next, we systematically studied signal transduction events including: tyrosine phosphorylation, Ca++ flux, and ceramide production in the JM and JMRE sublines. The tyrosine phosphorylation patterns and the Ca++ influx generated following sIgM engagement were very similar in the JM and JMRE sublines. In contrast, the generation of ceramide differed in the PCD‐resistant and PCD‐susceptible sublines. Ceramide is produced following cross‐linking sIgM on WEHI‐231.7 JM cells and causes PCD. Ceramide levels in anti‐IgM‐treated WEHI‐231.7 JMRE cells are low and appear to be insufficient to induce PCD.
Hepatitis B virus small surface antigen particles are processed in a novel endosomal pathway for major histocompatibility complex class I‐restricted epitope presentation
Authors: Schirmbeck Reinhold , Melber Karl , Reimann Jörg 
Published: March 2007

AbstractWe investigated the major histocompatibility complex (MHC) class I‐restricted presentation of an epitope of the hepatitis B virus small surface (S) antigen particle to cloned murine cytotoxic T lymphocytes (CTL). Efficient Ld‐restricted presentation of the S28–39 epitope to CTL is observed in cells of different tissue origin pulsed in vitro, either with the antigenic S28–39 12‐mer S‐peptide, or with particulate S‐antigen. The kinetics of epitope presentation differ in S‐peptide‐pulsed and in S‐particle‐pulsed cells: while a 15‐min pulse with the antigenic peptide sensitizes targets for class I‐restricted CTL lysis, presentation of S‐particles requires 30–60 min to sensitize cells for CTL lysis. Uptake of antigenic material and active metabolism of the presenting cell are required for processing of S‐particles, but not for sensitizing targets with S‐peptides. Intracellular processing and presentation of S‐particles is blocked in cells treated with chloroquine, NH4Cl, primaquine, or leupeptin, but not by treatment with cycloheximide or brefeldin A. This processing pathway operates efficiently in peptide‐transporter‐deficient, Ld‐transfected T2 cells, revealing a novel endosomal/lysosomal processing pathway for class I‐restricted presentation of peptides derived from exogenous S‐particles.
Interleukin‐10 differentially regulates cytokine inhibitor and chemokine release from blood mononuclear cells and fibroblasts
Authors: Seitz Michael , Loetscher Pius , Dewald Beatrice , Towbin Harry , Gallati Harald , Baggiolini Marco 
Published: March 2007

AbstractIn this study we have examined the effects of interleukin‐10 (IL‐10) on blood mononuclear cells (MNC) and on skin as well as on synovial fibroblasts. In unstimulated MNC, we found that IL‐10 is a potent stimulator of interleukin‐1 receptor antagonist (IL‐1ra) and monocyte chemoattractant protein‐1 (MCP‐1) production and an inhibitor of IL‐8 release. In cells exposed to IL‐1β, it also moderately stimulated IL‐1ra production and release of soluble tumor necrosis factor receptor p75 (sTNF‐R p75) and inhibited IL‐8 and MCP‐1 production. In addition, we have evidence that the biological effects of IL‐10 are not restricted to hematopoietic cells. IL‐10 stimulated sTNF‐R p55 dose‐dependently and inhibited MCP‐1 release from IL‐1β‐activated fibroblasts, whereas IL‐8 production was not affected. Taken together, these findings identify novel biological actions of IL‐10 on blood mononuclear and connective tissue cells which support its regulatory functions as a suppressor of inflammatory processes.
Analysis of the fine specificity of rat, mouse and human TAP peptide transporters
Authors: Neefjes Jacques , Gottfried Eva , Roelse Joost , Grommé Monique , Obst Reinhard , Hämmerling Günter J. , Momburg Frank 
Published: March 2007

AbstractPrior to their association with major histocompatibility complex (MHC) class I molecules, peptides generated from cytosolic antigens need to be translocated by the MHC‐encoded peptide transporter (TAP) into the lumen of the endoplasmic reticulum (ER). While class I molecules possess well‐known binding characteristics for peptides, the fine specificity of TAP for its peptide substrates has not been analyzed in detail. Previously, we have studied the effect of amino acid variations at the N‐terminal, the C‐terminal, and the penultimate residue on the efficiency of peptide translocation. Using permeabilized cells, we have shown that TAP pre‐selects peptides in an allele‐ and species‐specific manner, for which only the C‐terminal residue is crucial. This finding is confirmed in the present study by using microsomes containing different TAP. The influence of amino acid substitutions at positions 2 to 7 of 9‐residue model peptides on TAP‐dependent peptide translocation is systematically examined. Only a few amino acid substitutions at these positions affect the efficiency of peptide translocation significantly, e.g. Pro at position 2 or 3 negatively influences transport whereas Glu at positions 6 and 7 enhances transport. The differences in translocation by the rat TAP alleles a or u, mouse TAP and human TAP are, however, minor for the peptide with internal substitutions used in this study. These results show that the C‐terminal residue essentially governs the species‐specific substrate specificity of TAP.
T cells made deficient in interleukin‐2 production by exposure to staphylococcal enterotoxin B in vivo are primed for interferon‐γ and interleukin‐10 secretion
Authors: Florquin Sandrine , Amraoui Zoulikka , Goldman Michel 
Published: March 2007

AbstractThe superantigen staphylococcal enterotoxin B (SEB) induces a defect in interleukin (IL)‐2 production by T cells expressing specific T cell receptor Vβ domains. The present study was undertaken to determine the capacity of T cells, made deficient in IL‐2 production by exposure to SEB in vivo, to secrete interferon (IFN)‐γ and IL‐10 and to induce pathology upon SEB rechallenge. For this purpose, BALB/c mice received two intraperitoneal injections of 100 μg SEB with a 48‐h interval. First, we compared peak serum levels of IL‐2, IFN‐γ and IL‐10 after SEB rechallenge with those measured after a single SEB injection in control mice. The expected defect in IL‐2 production in SEB‐pretreated mice was associated with a major increase in IL‐10 and IFN‐γ levels which were about fivefold higher than in controls. Experiments in mice depleted of CD4+ or CD8+ cells as well as studies in which purified T cell populations were rechallenged with SEB in vitro indicated that both CD4+ and CD8+ cells from SEB‐pretreated mice were primed for IL‐10 and IFN‐γ production. Furthermore, SEB‐pretreated mice were sensitized to the toxic effects of the superantigen as indicated by a 30‐70% lethality rate (vs. 0% in naive mice) within 48 h after SEB rechallenge. IFN‐γ was involved in the lethal syndrome as it could be prevented by injection of neutralizing anti‐IFN‐γ monoclonal antibody. We conclude that SEB‐reactive T cells made deficient for the production of IL‐2 by exposure to SEB in vivo are primed for IFN‐γ and IL‐10 production, and that IFN‐γ up‐regulation is involved in the shock syndrome occurring upon SEB rechallenge.
Co‐expression of B7‐1 and ICAM‐1 on tumors is required for rejection and the establishment of a memory response
Authors: Cavallo Federica , Martin‐Fontecha Alfonso , Bellone Matteo , Heltai Silvia , Gatti Evelina , Tornaghi Paola , Freschi Massimo , Forni Guido , Dellabona Paolo , Casorati Giulia 
Published: March 2007

AbstractAlthough the transfection of B7‐1 cDNA into a few mouse tumor cell lines can induce anti‐tumor T cell immunity, its expression alone is ineffective in many other tumor cell lines tested. We were interested to study what factors limit B7‐1 co‐stimulatory activity, and decided to investigate whether B7‐1 requires the cooperation of ICAM‐1 to provide the minimal co‐stimulatory signal for establishing an efficient anti‐tumor immunity. We show that the transfection of B7‐1 cDNA into three ICAM‐1+ (plasmocytoma J558L, T lymphomas EL‐4 and RMA), but not into two ICAM‐1− tumor cell lines (adenocarcinoma TS/A and melanoma B16.F1), is sufficient to induce their complete rejection in syngeneic mice. The expression of ICAM‐1 is necessary for the rejection of the B7 expressing tumors, since the primary response elicited by B7‐1+ EL‐4 and RMA clones expressing reduced levels of ICAM‐1 is severely reduced. Furthermore, super‐transfection of ICAM‐1 cDNA into B7‐1+ adenocarcinoma and melanoma clones optimizes their primary rejection. Histologic examination of transfected tumors reveals that B7‐1 and ICAM‐1 exert a potent pro‐inflammatory activity. The intra‐tumor infiltration is composed of both eosinophils and lymphomono‐cytes, and is already massive 5 days after the tumor challenge. The primary rejection of the B7‐1+ ICAM‐1+ tumors depends critically on CD8+ T cells, natural killer cells and granulocytes, but is independent of CD4+ T cells. Remarkably, in addition to its effects on the early phases of the immune response, the co‐expression of ICAM‐1 and B7‐1 on tumors is also necessary for the efficient induction of a memory response. In fact, only the primary challenge with B7‐1+, ICAM‐1+ tumor cells protects the majority of the mice from a second injection of parental tumor cells. Collectively, our findings indicate that B7‐1 and ICAM‐1 are fundamental components for triggering the primary rejection of tumors and establishing a protective memory response. These findings may help to define new strategies for the rational application of co‐stimulation in tumor immunotherapy.
Homotypic aggregation of murine B lymphocytes is independent of CD23
Authors: Davey Edward J. , Bartlett William C. , Kikutani Hitoshi , Fujiwara Hiroshi , Kishimoto Tadamitsu , Conrad Daniel H. , Severinson Eva 
Published: March 2007

AbstractCD23 is a low‐affinity receptor for IgE (FcϵRII). Functions attributed to CD23 not involving IgE suggest that it interacts with ligands other than IgE. CD21 has recently been described as a counter ligand for CD23. A number of lines of evidence have implicated CD23 as an adhesion molecule in human B cells. We have investigated the role of CD23 in homotypic B cell aggregation in the mouse, using lipopolysaccharide plus interleukin‐4‐induced aggregation as a model system. In this system high levels of aggregation are accompanied by a massive up‐regulation of CD23 expression. However, in contrast to what has been observed in human B cells, we find no evidence of a role for CD23 in homotypic adhesion of murine B cells.
Interleukin‐2 secretion by human B lymphocytes occurs as a late event and requires additional stimulation after CD40 cross‐linking
Authors: Kindler Vincent , Matthes Thomas , Jeannin Pascale , Zubler Rudolf H. 
Published: March 2007

AbstractWhile Epstein‐Barr virus (EBV)‐immortalized B cell lines have been shown to secrete interleukin (IL)‐2 after stimulation with either teleocidin or phorbol myristate acetate (PMA) and ionomycin, experimental conditions leading to IL‐2 production by normal human B cells have not been reported. In the present study we investigated various Bcell activating conditions, including – by analogy to EBV‐immortalized B lymphocytes – stimulation of B cells that are already proliferating (in cultures with IL‐4 and immobilized anti‐CD40 monoclonal antibody; the anti‐CD40 system). This approach showed that B lymphocytes secreted IL‐2 in the culture medium, but only if they were first activated for more than 24 h in the anti‐CD40 system before exposure to PMA plus ionomycin. The production rate of IL‐2 by B lymphocytes reached a maximum after 6 days of priming in such cultures followed by 48 h of stimulation with PMA plus ionomycin, corresponding to 7% or 15% of that of fresh CD4+ T cells activated, respectively, with phytohemagglutinin plus PMA, or with PMA plus ionomycin for 48 h. This IL‐2 production could not be attributed to T cell contamination nor to EBV‐infected B cells according to flow cytometric and reverse transcriptase‐polymerase chain reaction analysis of cultured B cells. Lower IL‐2 expression (detected only as mRNA synthesis) was also induced in the cultured B lymphocytes after incubation with cross‐linking anti‐IgM antibodies instead of PMA plus ionomycin. The appearance of IL‐13 mRNA, but not IL‐4 mRNA, was detected under the same stimulation conditions as for IL‐2 mRNA. These results show that the production of IL‐2 by normal B lymphocytes occurs as a late event relative to their activation and proliferation, and is in this respect subject to regulation different to that found in T lymphocytes.