bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trypanosoma cruzi‐infected macrophages are defective in major histocompatibility complex class II antigen presentation
Authors: La Flamme Anne C. , Kahn Stuart J. , Rudensky Alexander Y. , Van Voorhis Wesley C. 
Published: March 2007

AbstractTrypanosoma cruzi, the intracellular protozoan parasite that causes Chagas' disease, interferes with the host immune response to establish a persistent infection. In this report, we demonstrate that macrophages infected with T. cruzi are unable to effectively present antigens to CD4 T cells. The interference is due to defective antigen‐presenting cell (APC) function, as antigen‐independent stimulation of the T cell in the presence of infected macrophages is not affected. The defect is distal to antigen processing and is not due to decreased major histocompatibility complex (MHC) class II expression, decreased viability, defective peptide loading in the infected macrophages, nor absence of CD28 co‐stimulation. There was a role for gp39:CD40 co‐stimulation during antigen presentation to the T cells we studied, but the expression of CD40 on T. cruzi‐infected macrophages was not decreased. Antigen‐specific adhesion between macrophages and T cells was reduced by infection. Equivalent levels of the adhesion molecules lymphocyte function‐associated antigen‐1, intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1 or very late antigen‐4 are found on infected and uninfected APC, suggesting that reduced expression of these adhesion molecules was not responsible for the defect in antigen‐specific adhesion. The defective T cell:macrophage adhesion may be due to the reduced expression of other adhesion molecules or other changes in the cell induced by infection. Interfering with MHC class II antigen presentation in infected macrophages may help T. cruzi to blunt the immune response by the host.
Fetal and neonatal NK1.1+ Ly‐49− cells can distinguish between major histocompatibility complex class Ihi and class Ilo target cells: Evidence for a Ly‐49‐independent negative signaling receptor
Authors: Sivakumar Pallavur V. , Bennett Michael , Kumar Vinay 
Published: March 2007

AbstractNatural killer (NK) cell function is regulated by both positive and negative signaling receptors. In adult splenic NK cells, negative signaling has been shown to be mediated by the Ly‐49 family receptors. NK1.1+ 2B4+ CD3− cells that are phenotypically and functionally similar to adult splenic NK cells can be derived from murine fetal liver and thymus. These cells do not express any known Ly‐49 molecules on their surface nor do they contain the known Ly‐49 transcripts. Surface expression of Ly‐49 molecules is first detected on splenic NK1.1+ cells 4–6 days after birth. Despite the absence of these negative signaling receptors, fetal and neonatal Ly‐49− NK cells lyse TAP−/−, major histocompatibility complex (MHC) class Ilo but not TAP+/+, MHC class Ihi target cells. This suggests that fetal and neonatal NK cells express negative signaling receptors other than Ly‐49 molecules.
Polymerase chain reaction‐based identification of a novel serpin from human dendritic cells
Authors: Mueller Chris G. F. , Ho Steve , Massacrier Catherine , Lebecque Serge , Liu Yong‐Jun 
Published: March 2007

AbstractA subtraction library of CD40‐stimulated human tonsil dendritic cells has been constructed using a polymerase chain reaction approach adapted for low numbers of cells. From this library we identified a cDNA for a serine protease inhibitor, a serpin, which is absent from monocytes, B cells and T cells but expressed in CD40‐activated monocyte‐ and progenitor cell‐generated dendritic cells. In addition, the serpin is expressed in a lung fibroblast cell line and keratinocytes. Its mRNA is detected only in tonsil and thymus. The serpin described here reportedly functions as a megakaryocyte maturation factor in the presence of interleukin (IL)‐3 and IL‐11. This suggests that dendritic cells may promote the immune response by protecting IL‐3 and IL‐11 or other essential proteins from degradation.
Blockade of CD40‐CD40 ligand pathway induces tolerance in murine contact hypersensitivity
Authors: Tang Aimin , Judge Thomas A. , Turka Laurence A. 
Published: March 2007

AbstractInteractions between CD40 on antigen‐presenting cells and its ligand (CD40L) on T cells has been implicated in T cell‐mediated immune responses. Previously, we have shown that contact hypersensitivity (CHS), a cell‐mediated cutaneous immune response in reaction to haptens, could be subclassified based on whether the hapten primed for Th1 or Th2 cytokines in cells isolated from draining lymph nodes. We also found that tolerance to a Th2‐priming hapten could be induced only by simultane blockade of the CD40‐CD40L and B7‐CD28 at the time of sensitization. Here we demonstrate that blockade of CD40‐CD40L signaling alone induces long‐lasting unresponsiveness to the Th1 hapten 2,4‐dinitrofluorobenzene (DNFB), and inhibits antigen‐specific T cell proliferation in vitro. We find that CD40‐CD40L signaling is required in the sensitization but not elicitation phase of DNFB‐induced CHS, as treatment of mice with anti‐CD40L monoclonal antibody (mAb) does not affect the response to hapten challenge in previously sensitized and untreated animals. Examination of cytokine production shows that anti‐CD40L mAb decreases interferon‐γ production by draining lymph node cells from DNFB‐sensitized mice, and reciprocally increases interleukin (IL)‐4 production. Consistent with this Th1 to Th2 immune deviation, anti‐CD40L mAb prevents the induction of IL‐12 mRNA in regional lymph nodes, an event which is normally seen within 12 h following hapten sensitization. In contrast, suppression of CHS by CTLA4Ig decreased the production of all cytokines by draining lymph node cells. Together, these data show that blockade of the CD40‐CD40L pathway by itself is sufficient to induce tolerance to DNFB‐induced CHS, and that this is associated with blockade of IL‐12 induction and Th1 to Th2 immune deviation.
Anergic T cells effect linked suppression
Authors: Frasca Loredana , Carmichael Paul , Lechler Robert , Lombardi Giovanna 
Published: March 2007

AbstractAlthough the phenomenon of T cell‐mediated suppression is well established, particularly in experimental models of transplantation, the mechanisms involved in this form of immunoregulation remain controversial. We have recently demonstrated, using an in vitro system, that anergic T cells can act as suppressor cells by competing for the membrane of the antigen‐presenting cell (APC) and for locally produced interleukin‐2. In the experiments described here we have explored the ability of anergic T cells to effect linked suppression in antigen‐specific and allospecific responses. We observed that anergic antigen‐specific CD4+ T cells can inhibit T cells restricted by a different major histocompatibility complex (MHC) class II molecule provided that both restriction elements are expressed by the same APC. In addition, anergic allospecific clones could also effect linked suppression since they could regulate not only T cells specific for the same alloantigen but also responder T cells with direct allospecificity for a second allogeneic MHC molecule or with indirect, self MHC‐restricted allospecificity for a processed MHC class I alloantigen. Furthermore, the regulatory effect of the anergic T cells was dependent on cell contact, was not dependent upon irradiation, and was maintained during in vitro culture. These data demonstrate that linked suppression can be effected by anergic T cells in vitro. In the clinical context this raises the possibility that induction of tolerance to a single alloantigen could serve to regulate the immune response to an allograft carrying several MHC and minor antigen differences.
CDw78 — a determinant on a major histocompatibility complex class II subpopulation that can be induced to associate with the cytoskeleton
Authors: Rasmussen Anne‐Marie , Hořejši Václav , Levy Finn Olav , Blomhoff Heidi Kiil , Smeland Erlend B. , Beiske Klaus , Michaelsen Terje E. , Gaudernack Gustav , Funderud Steinar 
Published: March 2007

AbstractIn the present study we demonstrate that CDw78 monoclonal antibody (mAb) recognizes a distinct subpopulation of major histocompatibility complex (MHC) class II molecules. We show that the CDw78 epitope is present on less than 10 % of the total number of MHC class II molecules expressed on different cells, is not linked to a single isotype, and exhibits a characteristic expression pattern in tonsils. While mAb against MHC class II (DR, DP and DQ) stained the majority of cells both in the mantle zone and in germinal centers, the CDw78 staining was more heterogeneous with the strongest reactivity and the highest number of positive cells in the mantle zone and in the light centrocyte‐rich part of the germinal centers. Antibodies to this MHC class II subpopulation (e.g. FN1) induced association with the cytoskeleton and a subsequent capping in more than 90 % of peripheral blood B cells. In contrast, mAb against MHC class II (DR, DP and DQ) did not induce association with the cytoskeleton and only 10–20 % of B cells were induced to cap, suggesting that CDw78 defines a population of MHC class II molecules functionally different from the majority of these antigens. Scatchard plot analysis indicates that FN1 mAb is of relatively low affinity (Ka = 1.5 × 108M−1) and monovalent Fab fragments fail to bind to the cell surface with measurable affinity. Our data seen in the context of the ability of FN1 to co‐stimulate B cells with a suboptimal dose of anti‐μ suggest that CDw78 mAb might recognize a functional important subpopulation of MHC class II molecules so far not described. It seems likely that this subpopulation represents dimerized or aggregated MHC class II molecules that can selectively bind this low‐affinity mAb.
Enhanced follicular dendritic cell function in lymph nodes of simian immunodeficiency virus‐infected macaques: Consequences for pathogenesis
Authors: Rosenberg Yvonne J. , Lewis Mark G. , Greenhouse Jack J. , Cafaro Aurelio , Leon Enrique C. , Brown Charles R. , Bieg Kyle E. , Kosco‐Vilbois Marie H. 
Published: March 2007

AbstractHIV and simian immunodeficiency virus (SIV) infections are characterized by several abnormalities in B cell function. Pathogenesis is also associated with marked changes within germinal centers (GC) including hypertrophy and degeneration of follicular dendritic cells (FDC) and accumulation of both viral antigen and activated CD45RO+CD8+ cells. Since FDC are critical to the generation of antibody‐forming cells and specific B cell memory, the simplest assumption is that such B cell defects directly result from virus‐induced changes in the GC environment. The present study examined FDC‐enriched mesenteric lymph node lymphocyte preparations from early and late stage SIV‐infected and uninfected macaques for their ability to support GC reactions in vitro. The results indicate that FDC function as measured by cluster formation, B cell proliferation and SIV‐specific antibody production is enhanced in SIV‐infected macaques suggesting that, despite FDC atrophy, virus accumulation induces increased FDC‐B cell interactions resulting in B cell hyperactivity. The activation and proliferation of CD8+ cells in FDC‐enriched cultures further suggest that the infiltrating CD8+ population observed in situ in GC of late‐stage SIV/HIV‐infected individuals may also benefit from FDC‐derived growth signals. Thus, in addition to enhanced B cell proliferation and antibody production, hyperactivity of FDC may potentially promote their own self destruction via the infiltrating CD8+ cells. The increased B cell responsiveness may further exacerbate the disease process due to an overall decrease in the affinity of anti‐HIV/SIV antibody, a loss of crucial protective antibodies to other infectious agents and the creation of an environment in which increased trapping of virions facilitates more extensive infection of CD4+ T cells.
Genetic polymorphism of CCR5 gene and HIV disease: The heterozygous (CCR5/Δccr5) genotype is neither essential nor sufficient for protection against disease progression
Authors: Morawetz Renate A. , Rizzardi G. Paolo , Glauser Didier , Rutschmann Olivier , Hirschel Bernard , Perrin Luc , Opravil Milos , Flepp Markus , von Overbeck Jan , Glauser Michel P. , Ghezzi Silvia , Vicenzi Elisa , Poli Guido , Lazzarin Adriano 
Published: March 2007

AbstractHomozygous (Δccr5/Δccr5) and heterozygous (CCR5/Δccr5) deletions in the β‐chemokine receptor 5 (CCR5) gene, which encodes for the major co‐receptor for macrophage‐tropic HIV‐1 entry, have been implicated in resistance to HIV infection and in protection against disease progression, respectively. The CCR5/Δccr5 genotype was found more frequently in long‐term nonprogressors (LTNP) (31.0%) than in progressors (10.6%, p < 0.0001), in agreement with previous studies. Kaplan‐Meier survival analyses showed that a slower progression of disease, i.e. higher proportion of subjects with CD4+ T cell counts >500/μl (p = 0.0006) and a trend toward a slower progression to AIDS (p = 0.077), was associated with the CCR5/Δccr5 genotype. However, when LTNP were analyzed separetely, no significant differences in CD4+ T cell counts (p = 0.12) and viremia levels (p = 0.65) were observed between the wild‐type (69 % of LTNP) and the heterozygous (31.0 %) genotypes. Therefore, there are other factors which play a major role in determining the status of nonprogression in the majority of LTNP. Furthermore, there was no evidence that the CCR5/Δccr5 genotype was associated with different rates of disease progression in the group of progressors. Taken together, these results indicate that the CCR5/Δccr5 genotype is neither essential nor sufficient for protection against the progression of HIV disease.
Cross talk between T and B cells generates B antigen‐presenting cells able to induce inositol phosphate production in T cells responding to MIsa superantigens
Authors: O'Rourke Anne M. , Webb Susan R. 
Published: March 2007

AbstractPrevious studies showed that activation of CD4+ T cells with mouse mammary tumor virus‐encoded Mlsa superantigens induces strong proliferative responses and interleukin‐2 production but fails to elicit typical early T cell receptor (TCR)‐mediated signal transduction events, such as hydrolysis of polyphosphoinositides (PI) or an increase in intracellular calcium. Here we show that the failure of MIsa antigen to activate PI hydrolysis applies when resting B cells are used as antigen‐presenting cells (APC). By contrast, when MIsa‐bearing B cells are activated for 24h by exposure to lipopolysaccharide or, more importantly, to Mlsa‐reactive T cells or anti‐CD40 antibodies the cells develop the capacity to elicit easily detectable PI turnover. These studies demonstrate that, for B cells as APC, the initiation of certain TCR‐associated signal transduction pathways can depend on activation of the APC. The data suggest that cross talk between T cells and resting B cells can suffice to generate competent B APC and lead to the delayed initiation of signaling pathways important in T cell responses.
Murine model of IgE production with a predominant Th2‐response by feeding protein antigen without adjuvants
Authors: Ito Kazue , Inagaki‐Ohara Kyoko , Murosaki Shinji , Nishimura Hitoshi , Shimokata Tomoya , Torii Shinnpei , Matsuda Tukasa , Yoshikai Yasunobu 
Published: March 2007

AbstractStimulation of systemic antigen‐specific IgE production plays an important role in the mediation of food allergy; however, the mechanism of IgE production against food antigens is not fully understood. The development of relevant animal models may help to elucidate the pathogenesis of food allergy. We here show that DBA/2 mice receiving a casein diet without any adjuvant produced high levels of IgE specific for casein, accompanied by predominant Th2‐like responses in liver lymphocytes, mesenteric lymph node cells and spleen cells. This model of IgE production produced by feeding protein antigen as a constituent of the diet can be applied to investigate the mechanism of IgE production and to develop reagents for controlling food allergy.
A recombinant single chain antibody neutralizes coronavirus infectivity but only slightly delays lethal infection of mice
Authors: Lamarre Alain , Yu Mathilde W. N. , Chagnon Fanny , Talbot Pierre J. 
Published: March 2007

AbstractThe variable region genes of a murine anti‐coronavirus monoclonal antibody (mAb) were joined by assembly polymerase chain reaction and expressed in Escherichia coli in a single chain variable fragment (scFv) configuration. After induction of expression, the expected 32‐kDa protein was identified by Western immunoblotting with specific rabbit anti‐idiotype antibodies. The scFv fragments were purified from soluble cytoplasmic preparations by affinity chromatography on nickel agarose, which was possible with an N‐terminal but not with a C‐terminal histidine tag. Purified scFv fragments retained the antigen‐binding properties of the parental antibody, could inhibit its binding to viral antigens with apparently higher efficiency than monovalent antigen‐binding (Fab) fragments, but neutralized viral infectivity with lower efficiency (about sevenfold at a molar level). To evaluate the usefulness of these smaller and less immunogenic molecules in the treatment of viral diseases, mice were treated with purified recombinant scFv fragments and challenged with a lethal viral dose. A small delay in mortality was observed for the scFv‐treated animals. Therefore, even though the scFv could neutralize viral infectivity in vitro, the same quantity of fragments that partially protected mice in the form of Fab only slightly delayed virus‐induced lethality when injected as scFv fragments, probably because of a much faster in vivo clearance: the biologic half‐life was estimated to be about 6 min. Since a scFv derived from a highly neutralizing and protective mAb is only marginally effective in the passive protection of mice from lethal viral infection, the use of such reagents for viral immunotherapy will require strategies to overcome stability limitations.
Bacterial invasion induces interleukin‐7 receptor expression in colonic epithelial cell line, T84
Authors: Yamada Keiko , Shimaoka Motomu , Nagayama Kenichi , Hiroi Takachika , Kiyono Hiroshi , Honda Takeshi 
Published: March 2007

AbstractThe intestinal epithelial layer forms the interface between the external and the internal environments of a host. Since the interleukin‐7 (IL‐7) and IL‐7 receptor (IL‐7R) signaling pathway has been shown to play an important role in the mucosal immune system, we studied the expression of IL‐7R in T84, a colonic epithelial cell line, after cells were infected with several types of enteropathogenic bacteria, including Salmonella typhimurium, enteropathogenic Escherichia coli and enteroinvasive Escherichia coli. Bacterial invasion induced IL‐7R expression in T84 assessed by a semi‐quantitative reverse transcription‐polymerase chain reaction technique and flow cytometry. The inhibition of bacterial invasion by cytochalasin D, a specific inhibitor of actin polymerization, led to a reduction in the expression of IL‐7R. These data indicate that bacterial invasion into intestinal epithelial cells is likely to be an essential process in the induction of IL‐7R. The communication between the epithelium and mucosal lymphocytes which is mediated via IL‐7 and IL‐7R may be involved in the modulation of the mucosal inflammation which occurs in bacterial infection.
Induction of interleukin‐12 p40 transcript by CD40 ligation via activation of nuclear factor‐xB
Authors: Yoshimoto Takayuki , Nagase Hisashi , Ishida Takaomi , Inoue Jun‐Ichiro , Nariuchi Hideo 
Published: March 2007

AbstractInterleukin‐12 is produced in response to infection with bacteria or parasites or to bacterial constituents such as LPS in monocytes/macrophages and dendritic cells, and also generated by the interaction between activated T cells and antigen‐presenting cells via CD40–CD40 ligand (CD40L). So far, transcriptional analyses of p40 have been carried out only using bacterial constituents such as LPS as stimuli. In the present study, we have characterized the transcriptional induction of p40 by CD40 ligation in a human B lymphoblastoid cell line, Daudi, and a human acute monocytic leukemia cell line, THP‐1. These cells, stimulated by an agonistic monoclonal antibody against CD40 or by transfection with a CD40L expression vector, secreted p40 and showed enhanced p40 mRNA expression. Sequence analysis of the p40 promoter region identified two potential nuclear factor (NF)‐xB binding sites conserved between mouse and human. Electrophoretic mobility shift assay revealed that the potential NF‐xB binding sequence which is located around 120 bp upstream of the transcription initiation site in murine and human p40 genes formed an NF‐xB complex with nuclear extract from Daudi cells stimulated by CD40 ligation. Moreover, transfection of Daudi cells with the polymerized NF‐xB binding sequence ligated to a thymidine kinase/chloramphenicol acetyltransferase (CAT) reporter plasmid greatly induced CAT activity, but transfection with the polymerized mutated NF‐xB binding sequence did not. These results suggest that the NF‐xB binding site located around 120 bp upstream of the transcription initiation site in murine and human p40 promoter regions could be important for the p40 induction by CD40 ligation via activation of NF‐xB.
Processing of exogenous hepatitis B surface antigen particles for Ld‐restricted epitope presentation depends on exogenous β2‐ microglobulin
Authors: Schirmbeck Reinhold , Thoma Stefan , Reimann Jörg 
Published: March 2007

AbstractProcessing of exogenous hepatitis B surface antigen (HBsAg) particles in an endolysosomal compartment generates peptides that bind to the major histocompatibility complex (MHC) class I molecule Ld and are presented to CD8+ cytotoxic T lymphocytes. Surface‐associated ‘empty’ MHC class I molecules associated neither with peptide, nor with β2‐microglobulin (β2m) are involved in this alternative processing pathway of exogenous antigen for MHC class I‐restricted peptide presentation. Here, we demonstrate that internalization of exogenous β2m is required for endolysosomal generation of presentation‐competent, trimeric Ld molecules in cells pulsed with exogenous HBsAg. These data point to a role of endocytosed exogenous β2m in the endolysosomal assembly of MHC class I molecules that present peptides from endosomally processed, exogenous antigen.