bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cells specific for the myelin oligodendrocyte glycoprotein mediate an unusual autoimmune inflammatory response in the central nervous system
Authors: Linington Christopher , Berger Thomas , Perry Laura , Weerth Susanne , Hinze‐Selch Dunja , Zhang Yiping , Lu Hsi‐Chi , Lassmann Hans , Wekerle Hartmut 
Published: March 2007

AbstractMyelin oligodendrocyte glycoprotein (MOG)‐specific T cells mediate an autoimmune inflammatory response in the central nervous system (CNS) that differs radically from conventional models of T cell‐mediated experimental allergic encephalomyelitis (EAE). Using synthetic peptides an encephalitogenic T cell epitope of MOG for the Lewis rat was identified within the extracellular IgG V‐like domain of the protein, amino acids 44‐53 (FSRVVHLYRN).The adoptive transfer of CD4+ T cells specific for this epitope induce an intense, dose‐dependent inflammatory response in the CNS of naive syngeneic recipients. However, unlike the inflammatory response induced by myelin basic protein (MBP)‐specific T cell lines, inflammation mediated by the MOG peptide‐specific T cells failed to induce a gross neurological deficit.This unexpected observation was not due to a reduction in the overall inflammatory response in the CNS, but was specifically associated with a decrease in the extent of parenchymal (as opposed to perivascular) inflammation, a selective decrease in the number of ED1+ macrophages infiltrating the CNS, and a total lack of peripheral nerve inflammation. The decreased recruitment of macrophages into the CNS could not be ascribed to deficiences in the synthesis of interferon‐γ, tumor necrosis factor‐a, interleukin (IL)‐6 or IL‐2 by the T cell line. Moreover, this sub‐clinical inflammatory response induced severe blood‐brain barrier dysfunction as demonstrated by the induction of severe clinical disease following intravenous injection of a demyelinating MOG‐specific monoclonal antibody. The neurological deficit in EAE thus exhibits an unexpected dependence on the identity of the target autoantigen, which determines the extent and nature of the local inflammatory response and ultimately the extent of the neurological deficit.
The NH2‐terminal domain of rat CD2 binds rat CD48 with a low affinity and binding does not require glycosylation of CD2
Authors: Van Der Merwe P. Anton , McPherson Douglas C. , Brown Marion H. , Barclay A. Neil , Cyster Jason G. , Williams Alan F. , Davis Simon J. 
Published: March 2007

AbstractCD2, CD48 and CD58 are structurally similar cell adhesion‐molecules forming a subset of the immunoglobulin superfamily (IgSF). In humans CD58 is a ligand for CD2 while in mice CD2 binds CD48. We constructed a soluble chimeric molecule comprising the extracellular portion of rat CD48 and domains 3 and 4 of rat CD4 (sCD48‐CD4) and used it to examine whether CD2 is a ligand for CD48 in rats. sCD48‐CD4‐coated polystyrene Dynabeads™ formed rosettes on rat CD2‐transfected COS‐7 cells, and this rosetting was blocked by anti‐CD2 (OX34) and anti‐CD48 (OX45) monoclonal antibodies. We used sucrose‐gradient ultracentri‐fugation to show that sCD48‐CD4 binds, in solution, to soluble forms of rat CD2 including the single NH2‐terminal IgSF domain of rat CD2 expressed in bacteria. The upper limit of the affinity of the rat CD48‐CD2 interaction is 4 × 105 M−1, lower than the published affinity of human CD2 for CD58. These results show that rat CD48 binds CD2 on its NH2‐terminal IgSF domain with a low affinity and that binding is independent of glycosylation.
Repeated induction of nitric oxide synthase and leishmanicidal activity in murine macrophages
Authors: Cunha Fernando Q. , Assreuy Jamil , Xu Damo , Charles Ian , Liew Foo Y. , Moncada Salvador 
Published: March 2007

AbstractMurine macrophages express high levels of nitric oxide (NO) synthase and produce large amounts of NO when stimulated with interferon‐y plus lipopolysaccharide in vitro. The expression of NO synthase peaks at 12 h after stimulation and declines rapidly to the background level by 72 h. These macrophages can be repeatedly reactivated to express similar levels of NO synthase. The reactivation is not due to newly divided cells since peritoneal macrophages which do not divide in vitro and J774 cells cultured in the presence of colchicine can also be restimulated to express NO synthase. The reactivation is accompanied by re‐expression of NO synthase mRNA, as assessed by polymerase chain reaction analysis. Furthermore, the reactivated macrophages are fully capable of killing the intracellular protozoan parasite Leishmania major.
Inhibition of complement alternative pathway in mice with Fab antibody to recombinant adipsin/factor D
Authors: Pascual Manuel , Catana Emmanuelle , White Tyler , Spiegelman Bruce M. , Schifferli Jürg A. 
Published: March 2007

AbstractMouse adipsin is a serine protease secreted mainly by adipocytes. Similarly to factor D of human complement, it cleaves factor B. That adipsin is the equivalent of human factor D in the mouse is further suggested by their structural homology. Specific antisera against recombinant mouse adipsin (r‐adipsin) were produced in rabbits. Anti‐r‐adipsin IgG was shown to bind to radiolabeled r‐adipsin and to inhibit its hemolytic activity. In vitro, these antibodies Ab and Fab fragments thereof inhibited the adipsin/factor D hemolytic activity of mouse serum. They also blocked C3 activation induced by cobra venom factor (CVF), but did not interfere with classical pathway function. After intravenous injection of antir‐adipsin Fab into BALB/c mice, the adipsin/factor D hemolytic activity of serum was abolished during a 4‐h period. The C3 depleting effect of CVF injected intravenously was significantly delayed in BALB/c mice which had been pretreated with anti‐r‐adipsin Fab. These experiments demonstrate that mouse adipsin is the only form of mouse factor D and that anti‐r‐adipsin antibody can be used to produce a specific inhibition of the alternative pathway in vivo.
In vivo priming effect during various stages of ontogeny of an influenza A virus nucleoprotein peptide
Authors: Kuzu Hiroshi , Kuzu Yukiko , Zaghouani Habib , Bona Constantin 
Published: March 2007

AbstractIn vivo priming of cytotoxic T lymphocytes (CTL) by an influenza virus nucleoprotein (NP) peptide was studied at various stages of development. Adult mice immunized twice with the NP peptide in complete Freund's adjuvant and incomplete Freund's adjuvant, respectively, produce significant CTL responses. Neonates immunized at birth with large amounts of NP peptide and boosted twice with the peptide during adulthood, also mount a weak but significant CTL response. By contrast, offspring from mothers immunized with the NP peptide at days 15, 17, and 19 of pregnancy showed unresponsiveness to the peptide subsequent to a similar regimen of peptide immunization at the age of 1 month. The data indicate that the contact of T cell precursors with antigen during fetal life induces CTL tolerance, whereas, afterbirth the precursors are not susceptible to tolerogenic signals.
The gene loci for immunoglobulin heavy chains in precursor B cell lines from a patient with severe combined immunodeficiency appear able to participate in DNA rearrangement but have a germ‐line configuration
Authors: Kamachi Yoshiro , Ichihara Yoshikazu , Tsuge Ikuya , Abe Tokuichiro , Torii Shinpei , Kurosawa Yoshikazu , Matsuoka Hiroshi 
Published: March 2007

AbstractIn a previous study (Immunogenetics 1988. 27: 330) with Epstein‐Barr virus, we established lines of precursor B cells from bone marrow cells of a patient with severe combined immunodeficiency in whom the numbers of B cells and T cells were markedly reduced. Although based on their surface markers these cell lines appeared to be at an early stage of B cell differentiation, the gene loci for immunoglobulin heavy chains (IgH) retained the germ‐line configuration on both chromosomes in almost all the transformants. In this study, we found that the enhancer sequence, located between the Jh and μ genes, was hypomethylated and an abundance of the germ‐line Cμ transcript was detected in these cell lines by Northern hybridization. These results suggest that the chromatin structure of the IgH gene locus in these cell lines is accessible to VDJ recombinase and is able to participate fully in DNA rearrangement. By contrast, we did not detect transcripts of the RAG‐1 and RAG‐2 genes, which are required for V(D)J recombination at gene loci for immunoglobulin and T cell receptors. Thus, it seems likely that these cell lines fail to initiate the V(D)J recombination process because of some deficiency in the formation of VDJ recombinase, which includes the inability to express RAG genes.
The majority of human tonsillar CD5+ B cells express somatically mutated Vχ4 genes
Authors: Ebeling Saskia B. , Schutte Mieke E. M. , Logtenberg Ton 
Published: March 2007

AbstractWe have fractionated human tonsillar B cells on the basis of CD5 expression and determined the nucleotide sequences of immunoglobin light chain variable (V) regions encoded by the single member of the Vχ4 gene family in both CD5+ and CD5− populations. The majority of cDNA from both CD5+ and CD5− B cells populations harbored somatic mutations. Thus, human tonsillar CD5+ B cells, unlike their murine counterparts, are capable of activating their somatic hypermutation mechanism, resulting in the accumulation of somatic mutation in the VL regions.
The efficient bovine insulin presentation capacity of bone marrow‐derived macrophages activated by granulocyte‐macrophage colony‐stimulating factor correlates with a high level of intracellular reducing thiols
Authors: Frosch Stefanie , Bonifas Ursula , Eck Hans‐Peter , Bockstette Michael , Droege Wulf , Rüde Erwin , Reske‐Kunz Angelika B. 
Published: March 2007

AbstractBone marrow‐derived macrophages (BMMΦ) were shown before to function as antigen‐presenting cells. We show here, that the antigen presentation capacity of BMMΦ depends on the nature of the antigen and is differently regulated by the lymphokines interferon‐γ (IFN‐γ) and granulocyte/macrophage‐colony‐stimulating factor (GM‐CSF). When bovine insulin (BI) was employed as antigen, only BMMΦ treated with GM‐CSF (GM‐CSF‐MΦ) were efficient presenters, but when presentation of the antigens ovalbumin and conalbumin was tested, IFN‐γ‐pulsed BMMΦ (IFN‐γ‐M Φ) proved superior to GM‐CSF‐MΦ. The lack of efficient BI presentation function of IFN‐γ‐M Φ was only obvious, when native BI was used as antigen. Preprocessed BI was presented by IFN‐γ‐M Φ with drastically higher efficiency than by GM‐CSF‐M Φ Because processing of insulin depends on reduction of disulfide bonds, we analyzed the content of intracellular reducing thiols within IFN‐γ‐M Φ, GM‐CSF‐M Φ, and untreated BMMΦ. Only after stimulation with GM‐CSF did the amount of reduced glutathione and cysteine strongly increase, while IFN‐γ did not efficiently augment the intracellular content of both thiols. These findings suggest that the lymphokines IFN‐γ and GM‐CSF differently interfere with the processing capacity of BMMΦ by differently regulating the intracellular concentration of the thiols reduced glutathione and cysteine. A high level of these thiols induced by GM‐CSF correlates with a prominent capacity to present the antigen bovine insulin.
New simplified molecular design for functional T cell receptor
Authors: Brocker Thomas , Peter Annick , Traunecker Andre , Karjalainen Klaus 
Published: March 2007

AbstractWe have produced a chimeric single‐chain T cell receptor (TcR) that combines the specific antibody recognition function and TcR/CD3 signaling properties within the same polypeptide chain. This hybrid molecule consisted of a single‐chain antibody combining site that was connected over a short spacer to the transmembrane and cytoplasmic region of CD3ζ. When expressed on TcR− or TcR+ T cell hybridomas it could mediate recognition of relevent target cells and subsequent production of lymphokines; i.e. it could functionally replace the TcR/CD3 complex. Therefore, the single‐chain TcR model presented here represents an interesting and useful means for the creation of T cells with new specificities.
Selective disbalances of peripheral blood T lymphocyte subsets in human CD3γ deficiency
Authors: Timón Marcos , Arnaiz‐Villena Antonio , Rodríguez‐Gallego Carlos , Pérez‐Aciego Paloma , Pacheco Alberto , Regueiro Jose R. 
Published: March 2007

AbstractThe selection of T lymphocytes in the thymus and their activation upon the encounter with foreign antigens in the periphery require the aggregation and signals of the Tcell receptor (TcR)/CD3 complex and several surface molecules termed coreceptors (notably CD4 or CD8 and CD45). The spatial arrangement and interactions of the different molecules in the resulting multimolecular recognition structure are mostly unknown. Here we report, from studies on a healthy human CD3γ deficiency, that the lack of the CD3γ component of the TcR/CD3 complex is associated with a long‐term severe defect of peripheral blood CD4+CD45RA+ and CD8+ lymphocytes, whereas CD4+CD45RO+, B and natural killer lymphocytes are unaffected. These results suggest that the CD3y site of the TcR/CD3 complex is required for the peripheral representation of certain Tcell types.
Evidence that macrophages are programmed to die after activating autologous, cloned, antigen‐specific, CD4+ T cells
Authors: Richardson Bruce C. , Buckmaster Tarek , Keren David F. , Johnson Kent J. 
Published: March 2007

AbstractThe bone marrow produces large numbers of monocytes daily, but the mechanisms balancing production and elimination are unknown. In this report we demonstrate that macrophages (Mϕ) undergo apoptosis after activating autologous CD4+ cells. Since apoptosis is a genetically programmed response, these results argue that MΦ death can be part of a normal immune response. This event may have relevance to monocyte/Mϕ homeostasis, as well as immune response regulation and host defenses to intracellular organisms.
An NF‐χB‐like element plays an essential role in interleukin‐1‐mediated costimulation of the mouse interleukin‐2 promoter
Authors: Strieker Kirstin , Serfling Edgar , Krammer Peter H. , Falk Werner 
Published: March 2007

AbstractInterleukin‐1 (IL‐1) costimulation is required for efficient IL‐2 synthesis and IL‐2 receptor (IL‐2R) expression of T cells. The molecular events leading to these effects are largely unknown. We utilized an IL‐1‐responsive and an IL‐1‐non‐responsive subclone of the mouse thymoma cell line EL4 to investigate how IL‐1 activates IL‐2 gene expression. We correlated IL‐2 promoter activity with the activity of the endogenous IL‐2 gene, thereby showing the biological significance of our results. Our experiments provide new functional data showing that a major target of IL‐1 mediated costimulation is the χB‐like site, T cell element distal TCEd (GGGATTTCAC), of the IL‐2 promoter. Thus, deletion or mutation of TCEd within a complete IL‐2 promoter abrogated IL‐1 costimulation in the IL‐1 responsive EL4 subclone. Therefore. The TCEd element is functionally essential for the effect of IL‐1.We also identified a nuclear factor (NF), IL‐1 NF, that binds to the TCEd site after IL‐1 stimulation. This factor was only present in the IL‐1‐reponsive EL4 subclone and not in the IL‐1‐non‐responsive subclone after IL‐1 stimulation and did not appear after phytohemagglutinin (PHA)‐treatment. Binding of IL‐1 NF to the TCEd site was competed by a typical χB oligonucleotide, suggesting that it is similar to NF‐χB in its DNA‐binding properties. However, the TCEd element was only activated by costimulation with PHA and IL‐1 whereas a typical χB element was already activated by IL‐1 alone. These data suggest that the biological function of the TCEd element of the IL‐2 promoter differs from that of a canonical χB element. Our data provide new evidence that IL‐1 acts on the IL‐2 promoter by activating the TCEd element via the transcription factor IL‐1 NF. Furthermore, activation of this element requires two signals, delivered by IL‐1 and PHA, in this way reflecting the activation requirement for the endogenous IL‐2 gene.
Chemotaxins inhibit neutrophil adherence to and transmigration across cytokine‐activated endothelium: Correlation to the expression of L‐selectin
Authors: Moser René , Olgiati Licia , Patarroyo Manuel , Fehr Jorg 
Published: March 2007

AbstractNon‐activated neutrophils strongly adhere to cytokine‐activated human umbilical vein endothelial cells (HUVE). However, activation of neutrophils by different chemotactic mediators led to potent inhibition of this endothelial‐dependent interaction. For different formylated peptides, concentrations leading to maximal adherence inhibition coincided with those known for inducing maximal chemotactic migration of neutrophils. In terms of maximal adherence inhibition, a rank list was found in the order of N‐formyl‐Met‐Leu‐Phe > C5adesArg > interleukin‐8 > C5a ⩾ leukotriene B4, whereas platelet‐activating factor, and lipopolysaccharide showed no inhibition. This rank order was congruent to that of down‐regulation of neutrophil L‐selectin detected by the monoclonal antibody Leu‐8. Moreover, the dose‐dependent increase of neutrophil adherence inhibition corresponded to the loss of L‐selectin expression. Concentrations higher than that required for maximal inhibition led to a dose‐dependent decrease of inhibition, which was accompanied by increasing expression of neutrophil CD11/CD18. In contrast to the capacity of non‐activated neutrophils to migrate across interleukin‐1‐activated HUVE monolayers, transmigration was significantly impaired after chemotactic activation.
CDw50 and ICAM‐3: Two names for the same molecule
Authors: Juan Manel , Vilella Ramon , Mila Jordi , Yagüe Jordi , Miralles Agusti , Campbell Kerry S. , Friedrich R. Joachim , Cambier John , Vives Jordi , De Fougerolles Antonin R. , Springer Timothy A. 
Published: March 2007

AbstractCDw50 differentiation antigen is a molecule broadly expressed on hematopoetic cells but not on other cells. Previous experiments showed that CDw50 monoclonal antibodies (mAb) inhibited primary mixed lymphocyte culture (MLC). To understand the function of CDw50 better, we purified it and obtained peptide sequence. At the same time, intercellular adhesion molecule (ICAM)‐3, the third Iigand of lymphocyte function‐associated molecule 1, was described by mAb and subsequent cDNA cloning. Immunochemical, functional, and protein sequencing studies show that ICAM‐3 and CDw50 are the same glycoprotein, a 120‐kDa surface molecule with presumably an important role in the immune responses.
Activation with superantigens induces programmed death in antigen‐primed CD4+ class II+ major histocompatibility complex T lymphocytes via a CD11a/CD18‐dependent mechanism
Authors: Damle Nitin K. , Leytze Gina , Klussman Kerry , Ledbetter Jeffrey A. 
Published: March 2007

AbstractStaphylococcal enterotoxin superantigens (SAg) bind class II major histocompatibility complex (MHC) molecules on antigen‐presenting cells (APC) and upon cell‐to‐cell contact stimulate proliferation of T cells expressing appropriate Vβ gene products. In addition, SAg can also deliver negative signals to Ag‐specific T cells resulting in a state of unresponsiveness or a loss of viability. The present study examines the functional consequences of a direct interaction of SAg with alloAg‐specific class II MHC+ CD4+ T cell lines (TCL). Our results demonstrate that SAg induce programmed death (apoptosis) in a majority of Ag‐specific CD4+ T cells accompanied by genomic DNA fragmentation. SAg binding to Ag‐specific TCL resulted in a rapid mobilization of intracellular free calcium ([Ca2+]j) and transcription of a number of cytokine genes including interleukin‐2 (IL‐2), IL‐4, interferon‐γ (IFN‐γ), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), and granzyme B indicating the activation of primed T cells. Both SAg‐induced cytokine gene expression as well as subsequent death were significantly inhibited by a tyrosine kinase inhibitor herbimycin A and also by cyclosporin A. SAg‐induced death of primed T cells was also inhibited by monoclonal antibodies (mAb) directed at the CD11a/CD18 molecule but not those reactive with other T cell surface molecules such as CD2, CD7, CD28, CD29 or CD49d. None of these mAb, including anti‐CD11a/CD18, had any effect on SAg‐induced expression of IL‐2 and IL‐4 genes or SAg‐induced [Ca2+]i response. Addition of cytokines such as IL‐1a, IL‐2, IL‐4, IL‐6, GM‐CSF, IFN‐γ, tumor necrosis factor (TNF‐α, or TNF‐β), or neutralizing Ab to these cytokines had no effect on SAg‐induced death of Ag‐specific TCL. The T cells which survived the death‐inducing effects of SAg showed down‐regulation of the CD3/Tcell receptor and up‐regulation of CD2 and HLA‐DR expression, and upon re‐exposure to the same SAg upregulated expression of mRNA for IL‐2 and IFN‐γ. Presentation of SAg by B7+ ICAM‐1+ LFA‐3+ DR+ professional APC was also able to induce the death of Ag‐specific TCL. Together these results suggest that the activation with SAg causes programmed death of Ag‐specific TCL cells via a mechanism that requires late participation of the CD11a/CD18 molecule.
Multiple T cell specificities for Bet v I, the major birch pollen allergen, within single individuals. Studies using specific T cell clones and overlapping peptides
Authors: Ebner Christof , Schenk Siegfried , Szépfalusi Zsolt , Hoffmann Karin , Ferreira Fatima , Willheim Martin , Scheiner Otto , Kraft Dietrich 
Published: March 2007

AbstractTwenty‐five T cell clones specific for Bet v I were established from the peripheral blood of two birch pollen‐allergic patients. The T cell epitopes of these clones were mapped using dodecapeptides overlapping for 2 amino acids (neighbors share 10 residues) spanning the whole amino acid sequence of the protein (159 amino acids). In total, 7 epitopes could be detected. One donor displayed 6 distinct T cell specificities for the Bet v I molecule in 14 T cell clones; for the other donor, 4 stimulating peptides for 11 clones could be identified. Two T cell epitopes were recognized by both subjects. One of these might represent an immunodominant epitope located at amino acid position 77–92 of the Bet v I molecule, as in 13/25 T cell clones activation could be induced by this amino acid sequence. One T cell clone reacted with purified pollen‐derived Bet v I, but neither with any peptide synthesized according to a Bet v I‐encoding cDNA nor with the respective recombinant protein.Upon stimulation with allergen, the majority of the clones (21/24) revealed the THO or TH2 type of cytokine production (interleukin‐4 production), indicating their importance in the pathogenesis of the allergic disease.