bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of the immune response by nitric oxide differentially produced by T helper type 1 and T helper type 2 cells
Authors: Taylor‐Robinson Andrew W. , Liew Foo Y. , Severn Alison , Xu Damo , McSorley Stephen J. , Garside Paul , Padron Julio , Phillips R. Stephen 
Published: March 2007

AbstractThe balance between T helper type 1 (Th1) and T helper type 2 (Th2) cells determines the outcome of many important diseases. Using cloned murine T cell lines, evidence is provided that Th 1, but not Th 2, cells can be activated by specific antigens or a T cell mitogen, concanavalin A, to produce large amounts of nitric oxide (NO). Furthermore, NO can inhibit the secretion of interleukin (IL)‐2 and interferon‐γ by Th 1 cells but has no effect on IL‐4 production by Th 2 cells. Th 1 and Th 2 cells can, thus, be distinguished by their differential production of and susceptibility to NO. NO exerts a self‐regulatory effect on Th 1 cells which are implicated in immunopathology.
Defective T cell receptor/CD3 complex signaling in human type I diabetes
Authors: Maria Ruggero De , Todaro Matilde , Stassi Giorgio , Blasi Francesco Di , Giordano Marco , Galluzzo Aldo , Giordano Carla 
Published: March 2007

AbstractThe autoimmune process leading to the destruction of pancreatic β‐cells is mediated by T lymphocytes. Peripheral T cells from subjects with preclinical and clinical type I diabetes respond weakly in vitro to lectin stimulation. We, therefore, investigated in a group of newly diagnosed diabetic patients the presence of a defect in the signal transduction pathway of the T cell receptor (TcR)/CD3 complex.Following stimulation with anti‐CD3‐coupled beads, the proliferative response in diabetic T cells was significantly decreased in comparison with that from normal T cells. Interestingly, addition of either recombinant interleukin (IL)‐2 or phorbol 12‐myristate 13‐acetate to the cell culture was able to completely restore impaired anti‐CD3‐induced proliferation in diabetic T cells, suggesting the presence of a defect through the TcR/CD3 pathway, located upstream of protein kinase C (PKC) activation and resulting in low IL‐2 production and proliferation. Intracellular Ca2+ measurements by Fluo‐3 labeling and flow cytometry analysis on diabetic and control T cells after anti‐CD3 stimulation gave comparable results, indicating that this defect does not involve events leading to intracellular Ca2+ mobilization. In contrast, anti‐CD3 stimulation of diabetic T cells resulted in a marked impairment of PKC translocation and CD69 antigen expression, as assessed by peptide substrate phosphorylation and by flow cytometry analysis, respectively. Taken together, our data clearly show the presence in individuals at the onset of the disease of an in vitro defect in the signal transduction pathway of the TcR/CD3 complex, resulting in ineffective PKC activation which is not able to induce normal IL‐2 production and proliferation of diabetic T cells.
Adhesion molecules utilized in binding of intraepithelial lymphocytes to human enterocytes
Authors: Kelleher Dermot , Murphy Anne , Lynch Sara , O'Farrelly Cliona 
Published: March 2007

AbstractThe expression of adhesion molecules by human duodenal intraepithelial lymphocytes (IEL) was examined by two‐color flow cytometry. Resting IEL expressed LFA‐1, HML‐1, CD44. Stimulation with phytohemagglutinin (PHA) resulted in down‐regulation of expression of these molecules with induction of expression of ICAM‐1 and VLA‐4. VLA‐4 expression was also found on non‐activated IEL from patients with celiac disease. In addition, IEL expressed an antigen recognized by a novel monoclonal antibody D2.1. The molecular mass of D2.1 is heterogenous: 82 kDa in peripheral blood lymphocytes and 44 kDa in an IEL line. Expression of this antigen was also up‐regulated by PHA. To determine the involvement of these antigens in binding of IEL to human enterocytes, we developed a system based on adherence of an IEL cell line to the I407 fetal intestinal cell line. Monoclonal antibodies VLA‐4, D2.1 and to a lesser extent ICAM‐1 blocked adherence of IEL to I407 cells. These data suggest that VLA‐4 and D2.1 may be involved in adherence of IEL to human enterocytes or secreted matrix molecules in vivo.
Isolation of peritoneal precursors of B‐1 cells in the adult mouse
Authors: Marcos Miguel A. R. , Gaspar María L. , Malenchere Evelyne , Coutinho Antonio 
Published: March 2007

AbstractTwo weeks of daily peritoneopheresis of adult mice result in the selective depletion of B‐1 cells, followed by the appearance of a population of B220+IgM−lymphocytes in the peritoneal cavity. These cells share with bone marrow (BM) pre‐B cells expression of λ5, VpreB, and RAG‐1 genes and a higher fraction of unrearranged V to DJ heavy (H) chain immunoglobulin (Ig) gene segments, when compared with mature B lymphocytes. Upon transfer to SCID recipients, sorted peritoneal B220+IgM− cells fail to colonize the BM, repopulate very few B cells in the spleen, but entirely reconstitute the B‐1 cell compartment in the peritoneal and pleuropericardial cavities. In contrast, parallel transfers of sorted BM B220+IgM− cells result in reconstitution of the BM and spleen B lineage cell compartments, but in no coelomic B cell repopulation. Both types of pre‐B cells reconstitute splenic plasma cells of donor origin, but with markedly distinct efficiencies: the ratio of IgM‐plasma cell/B cell numbers in the spleens of peritoneal pre‐B cell recipients is more than 500‐fold higher than that of recipients reconstituted by BM pre‐B cells. We take these data to indicate that (1) differentiative commitment to the B‐1 cell population occurs before selection events on mature cells; (2) B‐1 precursors exist or may be locally produced in the adult mouse; (3) there is a lineage‐related differential ability of mature B cells to undergo terminal differentiation to high‐rate Ig secretion.
Dissection of T cell antigen receptor signaling using protein tyrosine kinase inhibitors
Authors: Baldari Cosima T. , Telford John L. 
Published: March 2007

AbstractT cell antigen receptor (TcR) recognition of appropriately presented antigen results in the rapid activation of protein tyrosine kinases. Subsequent events include activation of protein kinase C and increased intracellular free calcium which lead to the activation of transcription factors involved in regulating interleukin‐2 gene expression. We have assayed the ability of a panel of protein tyrosine kinase (PTK) inhibitors to interfere with activation of the NF‐AT transcription factor by TcR ligation or treatment with phorbol ester and calcium ionophore which bypass many of the early events of TcR signal transduction. The results indicate that PTK are involved in early and late stages of TcR signaling. Moreover, one inhibitor (genistein) revealed the existence of a PTK which down‐regulates specifically calcium‐mediated signaling at a point downstream of the PTK p56lck but upstream of calcium mobilization.
Analysis of susceptibility of mature human T lymphocytes to dexamethasone‐induced apoptosis
Authors: Tuosto Loretta , Cundari Enrico , Montani Maria Saveria Gilardini , Piccolella Enza 
Published: March 2007

AbstractWe present evidence that dexamethasone (Dex), a synthetic glucocorticosteroid, causes apoptosis in mature human T cells, similarly to what has been reported for murine T lymphocytes. Human T cell clones and short‐term activated T lymphocytes treated with Dex show the characteristic pattern of apoptotic cells, such as hypodiploid nuclei, chromatin condensation and DNA fragmentation into oligonucleosomal fragments. However, Dex susceptibility of T cells to apoptosis is cell cycle‐dependent. The progression in the proliferative cell cycle (G1 versus S) rescues Dex‐treated T cells from apoptosis. Moreover, occupancy of the T cell receptor reverses Dex‐induced apoptotic phenomena. These observations suggest that glucocorticoids contribute to the regulation of the proliferative or the suicidal response of antigen‐activated human T cells.
Attachment of oligosaccharides to peptide antigen profoundly affects binding to major histocompatibility complex class II molecules and peptide immunogenicity
Authors: Mouritsen Søren , Meldal Morten , Christiansen‐Brams Ida , Elsner Henrik , Werdelin Ole 
Published: March 2007

AbstractTo investigate the immunogenicity of glycopeptides, a peptide fragment from hen egg lysozyme, HEL(81–96)‐Y (here named 1) which is immunogenic in H‐2k mice and known to bind to the murine major histocompatibility complex (MHC) class II molecule Ek, was synthesized in five different glycosylated forms. The N‐terminal serine of HEL(81–96)‐Y was derivatized with D‐glucose (2), maltotriose (3), and a branched D‐glucose pentasaccharide (4). Furthermore, 1 was prepared with a central serine or asparagine derivatized with the branched D‐glucose pentasaccharide (5) and GlcNAc (6), respectively. The ability of the five glycopeptides and the non‐glycosylated peptide, labeled with 125I, to bind to the two MHC class II molecules, Ak and Ek, was studied using a gel filtration assay. None of them could bind to Ak. Neither 5 nor 6 were able to bind to Ek. Surprisingly 2, 3 and 4 bound better to Ek than did the non‐glycosylated peptide 1. The increased binding varied depending on the type of oligosaccharide attached to the N terminus of the peptide. The better binding to Ek of glycopeptide 4 was found to be due to an increased association rate. The binding of 1 as well as 4 was optimal at pH 5.0. Functional studies showed that 4 was able to elicit a heteroclitic proliferative response from T cells of mice immunized with the native non‐glycosylated peptide. Circular dichroism studies of 1 and 4 indicated a more unordered structure of 4 and a predominant α‐helical conformation of 1, suggesting that the MHC class II molecule may bind to peptides which are in a non‐α‐helical conformation. These results demonstrate that glycosylation has considerable influence on peptide immunogenicity for T lymphocytes.
Degeneracy of T cell receptor recognition of an influenza virus hemagglutinin epitope restricted by HLA‐DQ and ‐DR class II molecules
Authors: Jones Claerwen M. , Lake Richard A. , Lamb Jonathan R. , Faith Alex 
Published: March 2007

AbstractThe T cell receptor (TcR) recognizes antigens in the form of short peptide fragments bound to major histocompatibility (MHC) molecules. TcR have an immunoglobulin (Ig)‐like structure and, in an analogous manner to antigen recognition by Ig, the third complementarity determining regions (CDR3) of the TcR are believed to provide the primary contact with the peptide lying in the MHC groove. CDR1 and CDR2 are thought to contact the presenting MHC molecule. We have analyzed seven human CD4+ T cell clones that recognize a conserved peptide epitope (residues 255–270) within the influenza virus hemagglutinin (H3) HA1 subunit. Two T cell clones recognized the peptide in the context of HLA‐DRB1*1001 and HLA‐DQB1* 0602/DQA1*0102, respectively, and shared Vα, Vβ and Jβ gene segments. Only the junctional regions encoding the CDR3 regions of the two TcR chains were different. This suggests that the CDR3 regions of these TcR interact with the MHC class II molecule. Six of the T cell clones were restricted by the HLA‐DRB1*1001. Two of these T cell clones expressed Vβ9.1 and three expressed Vβ13 gene segments; the remaining clone expressed Vβ7.2, a close homologue of Vβ9.1. A diverse selection of Vα and J gene segments contributed to the junctional heterogeneity of the TcR, indicating a diversity of sequence combinations recognizing the epitope. Nevertheless, five out of six T cell clones bore a motif in the Vα CDR3 loop consisting of adjacent acidic and polar amino acid residues, eight residues from the carboxyl end of each CDR3.
Essential role for natural killer cells in the lethal lipopolysaccharide‐induced Shwartzman‐like reaction in mice
Authors: Heremans Hubertine , Dillen Chris , van Damme Jo , Billiau Alfons 
Published: March 2007

AbstractObservations in our laboratory have provided evidence that interferon‐γ (IFN‐γ) is a key regulator of inflammatory responses to bacterial lipopolysaccharide (LPS) (Heremans et al., J. Exp. Med. 1990. 171: 1853): treatment of mice with neutralizing monoclonal antibody against IFN‐γ was found to completely prevent lethal shock reactions, in particular the generalized Shwartzman reaction, whereas treatment with IFN‐γ sensitized the mice to the development of such reactions. Since activated T cells and natural killer (NK) cells are the main if not the only potential source of LPS‐induced IFN‐γ, we investigated the relative importance of these cells in the development of the generalized Shwartzman‐like reaction in mice by depleting them selectively with relevant monoclonal antibodies. Treatment with antibodies directed against the CD4+ T cell subset was not effective in protecting mice. Anti‐CD8 antibody did attenuate the reaction to some extent. However, markedly reduced mortality was seen in mice which were depleted of NK cells by systemic administration of polyclonal anti‐asialo GM1 or monoclonal anti‐NK1. 1 antibodies. Failure of T cells to promote the Shwartzman reaction was also evidenced by the observation that thymus‐less nude mice, which are deficient in T cells, were more rather than less sensitive to the reaction. Approximately 20 times less LPS was needed to induce the lethal reaction in these mice than in NMRI mice and 58 times more anti‐IFN‐γ antibody was required to block mortality. Nu/nu mice reportedly have an over‐active NK cell compartiment. IFN‐γ production by these cells in LPS‐treated mice may account for the augmented sensitivity. Our data suggest that NK cells may be the most important source of endogenous IFN‐γ which mediates the LPS‐induced lethal reactions in mice.
Interleukin‐10 controls interferon‐γ and tumor necrosis factor production during experimental endotoxemia
Authors: Marchant Arnaud , Bruyns Catherine , Vandenabeele Peter , Ducarme Martine , Gérard Catherine , Delvaux Anne , De Groote Donat , Abramowicz Daniel , Velu Thierry , Goldman Michel 
Published: March 2007

AbstractInterleukin‐10 (IL‐10) is a potent inhibitor of lipopolysaccharide (LPS)‐induced tumor necrosis factor (TNF) production and has been shown to protect mice from endotoxin shock. As IFN‐γ is another important mediator of LPS toxicity, we studied the effects of IL‐10 on LPS‐induced IFN‐γ synthesis in vitro and in vivo. First, we found that the addition of recombinant human IL‐10 (rhIL‐10) (10 U/ml) to human whole blood markedly suppressed LPS‐induced IFN‐γ release while neutralization of endogenously synthesized IL‐10 resulted in increased IFN‐γ levels. The ability of rIL‐10 to inhibit LPS‐induced IFN‐γ synthesis was also observed in vivo in mice. Indeed, administration of 1000 U recombinant mouse IL‐10 (rmIL‐10) 30 min before and 3 h after challenge of BALB/c mice with 100 μg LPS resulted in a threefold decrease in peak IFN‐γ serum levels. We then examined the production and the role of IL‐10 during murine endotoxemia. We found that LPS injection causes the rapid release of IL‐10, peak IL‐10 serum levels being observed 90 min after LPS challenge. Neutralization of endogenously produced IL‐10 by administration of 2 mg JES5‐2A5 anti‐IL‐10 monoclonal antibody (mAb) 2h before LPS challenge resulted in a marked increase in both TNF and IFN‐γ serum levels while irrelevant isotype‐matched mAb had no effect. The enhanced production of inflammatory cytokines in anti‐IL‐10 mAb‐treated mice was associated with a 60% lethality after injection of 500 μg LPS, while all mice pretreated with control mAb survived. We conclude that the rapid release of IL‐10 during endotoxemia is a natural antiinflammatory response controlling cytokine production and LPS toxicity.
Vaccination with T cell receptor peptides primes anti‐receptor cytotoxic T lymphocytes (CTL) and anergizes T cells specifically recognized by these CTL
Authors: Kuhröber Andreas , Schirmbeck Reinhold , Reimann Jörg 
Published: March 2007

AbstractWe selected three peptides from the germ‐line sequence of the Vβ8.2 and Jβ2.3 gene segments of the murine T cell receptor for antigen (TCR) which contained putative Kd‐ and Ld‐restricted epitopes. Immunization of BALB/c (H‐2d) mice with the Vβ8.2(67–90) 23‐mer peptide 1 as well as the 15‐mer Vβ8.2(95–108)‐peptide 2 efficiently primed specific CD8+ cytotoxic T lymphocyte (CTL) responses in vivo against natural TCR‐Vβ8.2 epitopes. Vβ8.2+ T cells were not deleted in TCR peptide‐immunized mice because the fractions of Vβ8.2+ CD4+ and Vβ8.2+ CD8+ T cells in spleen and lymph nodes were not altered. The proliferative response of Vβ8.2+ T cells to stimulation by monoclonal antibody F23.2 was selectively suppressed (by 60–80%) in peptide‐immunized BALB/c mice, indicating partial anergy of this T subset. Immunization of BALB/c mice with the Jβ2.3‐derived peptide 3 stimulated a CD8+ CTL response against a class I‐restricted epitope within this Jβ segment that was also generated during natural “endogenous” processing of this self antigen. These data confirm the predictive value of major histocompatibility complex class I allele‐specific motifs. The described experiments indicate that TCR peptide‐primed CD8+ CTL recognize class I‐restricted, natural Vβ/Jβ‐TCR epitopes. Such anti‐TCR CTL may, thus, operate in Vβ‐specific immunoregulation of the T cell system suppressing their functional reactivity without deleting them.
T cell allorecognition and endogenous HLA‐B27‐bound peptides in a cell line with defective HLA‐B27‐restricted antigen presentation
Authors: López Daniel , García‐Hoyo Rosa , García Fernando , De Castro José A. López 
Published: March 2007

AbstractThe B*2702+ lymphoblastoid cell line NW is unable to present at least some HLA‐B27‐restricted viral antigens to T cells. This defect was genetically inherited, and was suggested to be related to the nature of the HLA‐B27 binding peptides reaching the endoplasmic reticulum in these cells (Pazmany et al., J. Exp. Med. 1992. 175: 361). In the present study 17 of 19 HLA‐B27‐specific alloreactive cytotoxic T lymphocyte clones recognizing the B*2702 subtype on other cells also lysed NW cells. Only two cytotoxic T lymphocyte clones failed to lyse NW while efficiently killing other B*2702+ cell lines. The high‐performance liquid chromatography profiles of the B*2702+ bound peptides extracted from NW cells was similar, but not identical, to those from two other cell lines. These results indicate that the HLA‐B27‐bound peptide repertoire in NW cells is not fundamentally different from those in other B*2702+ cells. Our data argue against gross differences in peptide processing or transport as being responsible for the defective presentation of particular HLA‐B27‐restricted viral antigens to T cells, but do not rule out distinct presentation of some endogenous peptides. Differences in the capacity to present certain peptides could cause differential susceptibility among HLA‐B27+ individuals to ankylosing spondylitis.