bluuebunny/crossref_metadata_2025_split huggingface dataset:
The microbicidal activity of interferon‐γ‐treated macrophages against Trypanosoma cruzi involves an L‐arginine‐dependent, nitrogen oxide‐mediated mechanism inhibitable by interleukin‐10 and transforming growth factor‐β
Authors: Gazzinelli Ricardo T. , Oswald Isabel P. , Hieny Sara , James Stephanie L. , Sher Alan 
Published: March 2007

AbstractThe present study was carried out to determine the effector mechanism of anti‐Trypanosoma cruzi activity by interferon (IFN)‐γ plus lipopolysaccharide (LPS)‐treated macrophages. A macrophage cell line (IC‐21) that failed to mount an appreciable oxidative burst was nevertheless found able to control T. cruzi growth after exposure to IFN‐γ alone or IFN‐γ plus LPS. Moreover, microbicidal functions of both inflammatory macrophages and IC‐21 against T. cruzi was found to be inhibited in the presence of NG‐monomethyl‐L‐arginine (NGMMA), a competitive inhibitor of L‐arginine. Addition of supplemental L‐arginine to the culture overcame the capacity of NGMMA to block activated macrophage anti‐T. cruzi functions. The ability of NGMMA to reverse both parasite growth inhibition and killing by IFN‐γ plus LPS‐activated macrophages was found to correlate with the suppression of nitrite accumulation in the culture supernatants. Together, these results implicate the L‐arginine‐dependent production of nitric oxide in T. cruzi killing by activated macrophages. We also tested the ability of interleukin(IL)‐10 and transforming growth factor (TGF)‐β, to block regulation of T. cruzi growth in this system. Both IL‐10 and TGF‐β inhibited anti‐parasite function by IFN‐γ‐activated macrophages, with an optimal dose of 100 units/ml and 0.5 ng/ml, respectively. Moreover, when used in combination, suboptimal doses of IL‐10 and TGF‐β were found to produce a synergistic inhibitory effect in the regulation of T. cruzi growth. The ability of IL‐10 and TGF‐β to suppress microbicidal function was also positively correlated with inhibition of nitrite generation in macrophage culture supernatants. These results predict an in vivo role for IL‐10 and TGF‐β in promoting parasite survival in the face of the host cell‐mediated immune response.
A trypsin‐like serine protease activity on activated human B cells and various B cell lines
Authors: Biró Anna , Sármay Gabriella , Rozsnyay Zoltán , Klein Eva , Gergely János 
Published: March 2007

AbstractWe have studied the trypsin‐like serine protease activity of human tonsillar B lymphocytes. The lysate of the low‐density, in vivo activated B cells as well as the lysate of cells stimulated with anti‐human IgM F(ab')2 show elevated trypsin‐like serine protease activity compared to the resting subset as monitored by the cleavage of Tos‐Gly‐Pro‐Arg‐pNA. The cleavage is sensitive to N‐tosyl‐L‐lysyl‐chloromethyl ketone and benzamidine but not to iodoacetamide. Experiments with intact cells give similar results. The finding that the intact cells hydrolyze the substrate, while their supernatant does not, suggests that the protease activity is cell membrane associated. It is possible that C3 is a substrate of the enzyme since the activated B cells cleave C3, whereas the resting B cells do not, and also C3 inhibits the enzyme‐substrate reaction.In addition to the ex vivo B cells, we studied the serine protease activity of certain well‐characterized B cell lines. The results show a correlation between the phenotype and the enzyme expression of the cell lines. BL41, an Epstein‐Barr virus (EBV)‐negative Burkitt lymphoma line, with a resting phenotype, has low activity, while its EBV genome‐carrying convertants E95‐A‐BL41, E95‐C‐BL41, EHR‐A‐BL41 and BL41/95 that have the phenotype of activated B cells, have high proteolytic activity. The lymphoblastoid cell line WW‐1‐LCL which has the phenotype of an immunoblast, has the highest serine protease activity.On the basis of the above data, we suggest that a rather tight correlation exists between the degree of activation and the appearance of serine protease(s) on the surface of human B cells.
Evolution of vertebrate IgM: complete amino acid sequence of the constant region of Ambystoma mexicanum μ chain deduced from cDNA sequence
Authors: Fellah Julien S. , Wiles Michael V. , Charlemagne Jacques , Schwager Joseph 
Published: March 2007

AbstractCDNA clones coding for the constant region of the Mexican axolotl (Ambystoma mexicanum) μ heavy immunoglobulin chain were selected from total spleen RNA, using a cDNA polymerase chain reaction technique. The specific 5′‐end primer was an oligonucleotide homologous to the JH segment of Xenopus laevis μ chain. One of the clones, JHA/3, corresponded to the complete constant region of the axolotl μ chain, consisting of a 1362‐nucleotide sequence coding for a polypeptide of 454 amino acids followed in 3′ direction by a 179‐nucleotide untranslated region and a polyA+ tail. The axolotl Cμ is divided into four typical domains (Cμ1‐Cμ4) and can be aligned with the Xenopus Cμ with an overall identity of 56% at the nucleotide level. Percent identities were particularly high between Cμ1 (59%) and Cμ4 (71%). The C‐terminal 20‐amino acid segment which constitutes the secretory part of the μ chain is stronglyhomologous to the equivalent sequences of chondrichthyans and of other tetrapods, including a conserved N‐linked oligosaccharide, the penultimate cysteine and the C‐terminal lysine. The four Cμ domains of 13 vertebrate species ranging from chondrichthyans to mammals were aligned and compared at the amino acid level. The significant number of μ‐specific residues which are conserved into each of the four Cμ domains argues for a continuous line of evolution of the vertebrate μ chain. This notion was confirmed by the ability to reconstitute a consistent vertebrate evolution tree based on the phylogenic parsimony analysis of the Cμ4 sequences.
Modulation of integrin expression during mast cell differentiation
Authors: Ducharme Lori A. , Weis John H. 
Published: March 2007

AbstractPreviously we have reported that rodent mast cells synthesize the mRNA encoding the α and β integrin chains (α4, β1 and β7) of the lymphocyte Peyer's patch adhesion molecule (LPAM)‐1 and LPAM‐2 lymphocyte homing receptors, and that they possess an α4‐containing integrin complex on their cell surface. In this report, we have examined the expression of these integrin chain genes by mature connective tissue mast cells (CTMC) and by bone marrow‐derived mast cells (BMMC) differentiated from bone marrow precursor cells in the presence of interleukin (IL)‐3 and/or the c‐kit ligand (also known as mast cell growth factor and stem cell growth factor). High levels of both the β7 and β1 transcripts were present in mature CTMC while those encoding the α4 chain were absent. Similarly, when BMMC were grown in IL‐3 for 28 days and analyzed for integrin chain transcripts, those specific for the α4 chain were also diminished compared to β7 and β1 transcripts. To compare the expression of these integrin genes during mucosal mast cell and CTMC development, BMMC were derived in the presence of IL‐3 alone, c‐kit alone, or IL‐3/c‐kit together. These experiments indicated that c‐kit inhibited the transcription of the β7 and FcεRI genes while enhancing α4 transcript levels. The enhancement of α4 levels, however, was abrogated with the addition of IL‐3. Similarly, the c‐kit‐induced depression of β7 and Fcε RI transcript levels was overcome by the addition of IL‐3. These data suggest that the integrin complexes synthesized by the mast cells may differ depending upon their path of differentiation and that another α chain integrin may be synthesized to complex with the β7 and/or β1 chains.
Limited involvement of interleukin‐6 in the pathogenesis of lethal septic shock as revealed by the effect of monoclonal antibodies against interleukin‐6 or its receptor in various murine models
Authors: Libert Claude , Vink Anne , Coulie Pierre , Brouckaert Peter , Everaerdt Bart , Van Snick Jacques , Fiers Walter 
Published: March 2007

AbstractSeveral studies in human patients and in laboratory animals have revealed a correlation between serum interleukin (IL)‐6 levels and outcome in clinical sepsis and in related animal models, respectively. In the present study, two monoclonal antibodies were used to investigate the contribution of IL‐6 in the lethal action of tumor necrosis factor (TNF) and of lipopolysaccharide (LPS) in mice. We studied the potential protective properties of an anti‐murine (m) IL‐6 antibody and of an anti‐mIL‐6 receptor antibody. In controlled experiments, we observed that both monoclonal antibodies conferred a dose‐dependent protection to a lethal dose of mTNF. Detailed studies with the monoclonal antibodies indicate, however, that protection was no longer observed when the mTNF dose was slightly higher than the lethal dose. Likewise, the anti‐IL‐6 monoclonal antibody protected against injections of LPS at a lethal‐dose concentration, but here too failed to protect against higher doses of LPS. The anti‐IL‐6 monoclonal antibody was unable to protect against mTNF in mice sensitized by galactosamine, the corticoid receptor antagonist RU38486 or human (h) IL‐1β. Protection did not correlate with the serum concentrations of IL‐6. Finally, we demonstrate that hIL‐6 injection did not change the sensitivity of mice towards mTNF. We conclude that, although IL‐6 levels may be of value as a marker for the outcome in septic shock, this cytokine contributes only marginally in the pathogenesis leading to death. The small, but real, contribution of IL‐6 in some situations might be due to its ability to up‐regulate the level of TNF receptors.
Dissection of major histocompatibility complex (MHC) and T cell receptor contact residues in a Kb‐restricted ovalbumin peptide and an assessment of the predictive power of MHC‐binding motifs
Authors: Jameson Stephen C. , Bevan Michael J. 
Published: March 2007

AbstractThe effect of alanine substitution on the major histocompatibility complex (MHC) binding and T cell receptor recognition of the Kb‐restricted ovalbumin 257–264 peptide was investigated. Positions 3, 5 and 8 of the octamer were important for Kb binding, as predicted from the motifs found in Kb‐associated peptides, while mutations at positions 4, 6 and 7 affected cytotoxic T lymphocyte recognition. Substitutions at positions 1 and 2 had very minor effects on T cell recognition. In addition, we tested the capacity of sequence motifs to predict MHC binding by analysis of a series of peptides which all bear the minimal Kb motif. We found that possession of good motifs was not always sufficient to give strong MHC binding, indicating secondary effects of the residues flanking the „MHC anchor”︁ positions.
CD44 can be activated to function as an hyaluronic acid receptor in normal murine T cells
Authors: Lesley Jayne , Hyman Robert 
Published: March 2007

AbstractThe hyaluronic acid (HA)‐binding function of CD44 expressed on the cell surface of normal hematopoietic cells has been studied by assaying binding of fluoresceinated hyaluronic acid (FI‐HA) and adhesion to immobilized HA. As has been observed previously, normal hematopoietic cells from bone marrow and spleen do not constitutively bind HA. A CD44‐specific monoclonal antibody, IRAWB 14, which has been shown to rapidly induce HA binding in some CD44+ cell lines, was used to activate the HA‐binding function of CD44 in these normal cells. Only splenic T cells were activated by the IRAWB 14 antibody to bind FI‐HA. Upon activation, FI‐HA binding correlated with the level of CD44 expression.Activation of HA binding allowed splenic T cells to adhere to HA immobilized on plastic and to an endothelial cell line in an HA‐dependent manner. BALB/c and AKR/J splenic T cells differ in their level of CD44 expression, and this correlated with differences in their ability to bind HA upon antibody activation. The minor subpopulation of MEL‐14− T cells were among the brightest Fl‐HA‐staining cells.We propose, on the basis of these and other results, that there are three states of CD44 function with respect to HA binding: (a) a non‐activatable, resting state, which cannot be rapidly activated to bind HA, as seen in most hematopoietic cells; (b) an activatable state, which can be rapidly converted to HA‐binding function, in this case by the IRAWB 14 antibody, illustrated by T cells as shown here; and (c) a constitutively active state, which can bind HA without antibody activation, seen in some cell lines.
Factors modifying survival pathways of germinal center B cells. Glucocorticoids and transforming growth factor‐β, but not cyclosporin A or anti‐CD19, block surface immunoglobulin‐mediated rescue from apoptosis
Authors: Holder Michelle J. , Knox Kirstine , Gordon John 
Published: March 2007

AbstractThe tendency for germinal center (GC) B cells to enter apoptosis is suppressed on engaging antigen receptor with immobilized anti‐immunoglobulin; cross‐linking of surface CD40 by monoclonal antibodies provides an additional signal for rescuing GC cells from programmed death. These observations are believed to reflect events that, in vivo, would allow for the selection of centrocytes which have undergone somatic mutation on Ig V‐region genes to generate antigen receptor of high affinity. The purpose of the present study was to identify factors capable of modifying the survival pathways of GC cells. Transforming growth factor‐β, at an optimal concentration of 1 ng/ml, was found to inhibit surface immunoglobulin (sIg)‐mediated rescue of GC cells but had no influence on survival promoted through CD40. Both routes of rescue were blocked by the glucocorticoid prednisolone at pharmacological concentrations (ID50 = 10−7 M). Cyclosporin A, an antagonist of sIg‐mediated signaling in resting B cells, failed to block rescue of GC cells through either of the receptor‐activated pathways. Antibody to CD19‐which also suppresses the activation of resting B cells ‐ not only left GC cell rescue undiminished, but rather provided a modest survival signal of its own; interferon‐α behaved similarly while interferon‐γ failed to influence GC cell survival in either direction.
Environmental influence on T cell receptor α gene rearrangement and expression in vitro
Authors: Larché Mark , Rencher Samantha D. , Hurwitz Julia L. 
Published: March 2007

AbstractExperiments were designed to test whether T cell progenitors are committed to particular T cell receptor (TcR) gene rearrangement and expression patterns (prior to rearrangement) or whether such patterns are molded by the thymic microenvironment in which T cells develop. To this end, day 14 fetal thymocytes were removed from their normal environment and grown in organ culture (FTOC) for 5 to 12 days. RNA was extracted from organ‐cultured cells, processed to cDNA, and TcR α sequences were amplified by the polymerase chain reaction for cloning and sequening. By the examination of N‐region additions and V‐gene usage, and by the comparison of resultant patterns with those of early vs. adult stages of T cell differentiation in vivo, it was demonstrated that thymocytes in FTOC did not maintain early patterns of gene rearrangement. The thymocyte patterns were most dissimilar from those of normal, early ontogeny when interleukin‐4 was added to FTOC. Taken together, results demonstrated the flexibility of T cell progenitors and that environment plays a critical role in the molding of TcR α rearrangement and expression patterns.
c‐myc‐induced natural killer cell sensitivity of human melanoma cells is reversed by HLA‐B27 transfection
Authors: Peltenburg Lucy T. C. , Steegenga Wilma T. , Margaretha Krüse K. , Schrier Peter I. 
Published: March 2007

AbstractIn human melanoma, activation of the c‐myc oncogene results in locus‐specific down‐modulation of the HLA‐B antigen expression. Moreover, overexpression of c‐myc induces an increase of natural killer (NK) sensitivity of the tumor cells. To show that this effect on susceptibility to NK cells is mediated by the downmodulation of the HLA‐B expression rather than by the activation of the oncogene, we supertransfected a c‐myc transfectant with the gene encoding the HLA‐B27 protein. The resulting supertransfectants with HLA‐B27 surface expression were all less sensitive to NK cells than their parental cell line and showed a level of resistance equal to the original melanoma cell line with low c‐myc expression. This indicates that the induction of NK sensitivity by c‐myc activation in human melanoma cells is mediated through down‐modulation of the HLA‐B expression. These data also imply differential effects of HLA‐A and HLA‐B molecules on lysis by NK cells, because the level of NK susceptibility can apparently be defined by the level of HLA‐B, irrespective of a substantial level of HLA‐A expression present in the tumor cells.
Immunoglobulin VH‐T cell receptor Cα fusion mRNA resulting from chromosome inversion include the T cell‐associated 5′ exon ET
Authors: Fisch Paul , Foroni Letizia , Forster Alan , Lavenir Isabelle , Mengle‐Gaw Laurel , Rabbitts Terence H. 
Published: March 2007

AbstractA human T cell lymphoma has been described in which an inversion of chromosome 14 results in fusion of an immunoglobulin heavy chain VH with a T cell receptor Jα segment, potentially resulting in a chimeric protein with immunoglobulin VH region recognition plus T cell receptor effector functions. Examination of the mRNA species expressed from the IgT gene in this lymphoma shows a variety of forms but all IgT mRNA include the T cell‐specific exon, ET, previously located in the distal part of the VH locus. In such mRNA species, the normal leader exon of the Ig VH segment, which encodes most of the hydrophobic signal peptide, is replaced by the short ET exon encoding mainly non‐hydrophobic residues. Two forms of this mRNA exist which lack the Ig VH leader sequence and thus potentially yield non‐membrane proteins in the T cell lymphoma.
Human Golgi β‐galactoside α‐2,6‐sialyltransferase generates a group of sialylated B lymphocyte differentiation antigens
Authors: Keppler Oliver T. , Moldenhauer Gerhard , Oppenländer Monika , Schwartz‐Albiez Reinhard , Berger Eric G. , Funderud Steinar , Pawlita Michael 
Published: March 2007

AbstractThe role of the human β‐galactoside α‐2,6‐sialyltransferase (hu α‐2,6‐ST) in the generation of B cell surface antigens was investigated by selecting subclones of COS cells (monkey kidney epithelial cells) constitutively expressing a transfected cDNA which encodes the hu α‐2,6‐ST (COS α‐2,6‐ST cells). Expression of hu α‐2,6‐ST in COS cells was sufficient to generate sialylated cell surface epitopes on different glycosylated antigens recognized by monoclonal antibodies to CDw75, CD76, and the unclustered monoclonal antibodies HB‐4 and EBU‐65. These epitopes were sensitive to sialidase treatment and are likely to contain terminal α‐2,6‐linked sialic acid residues. A novel antiserum raised against bacterially expessed hu α‐2,6‐ST fusion protein was used to localize the sialyltransferase in two cell lines with high expression of either endogenous (B cell line JOK‐1) or recombinant (COS α‐2,6‐ST cells) hu α‐2,6‐ST. In both cell lines, the enzyme was detected only intracellularly in the juxtanuclear region and not on the cell surface. In contrast, CDw75, formerly proposed to be identical with an α‐2,6‐ectosialyltransferase, was strongly expressed on the cell surface. The different expression patterns show that neither the CDw75 antigen nor any of the other sialylated antigens analyzed is identical with the hu α‐2,6‐ST. Furthermore, the presence of a surface‐expressed α‐2,6‐ST appears unlikely in these cell lines. We propose that CDw75, CD76, HB‐4, and EBU‐65 represent a unique group of B cell differentiation antigens the production of which requires the enzymatic activity of α‐2,6‐ST.
Interleukin‐3‐treated non‐B, non‐T cells switch activated B cells to IgG1/IgE synthesis
Authors: Ledermann Fritz , Heusser Christoph , Schlienger Claude , Le Gros Graham 
Published: March 2007

AbstractThe switch of activated B cells to IgE synthesis is an interleukin (IL)‐3‐dependent process. It is currently thought that specific T cells activated by antigen presented in the context of class II major histocompatibility complex are the major source of IL‐4. Recently it has been demonstrated that a splenic non‐T non‐B cell population (termed NBNT) has the capacity to produce IL‐4 following IgE and IgG receptor cross‐linkage. In this study we demonstrate that IL‐4 producing NBNT cells can induce the switch of lipopolysaccharide‐activated B cells to the synthesis of IgG1 and IgE antibodies. Furthermore, it was found that not only IgE receptor cross‐linkage but IL‐3 was able to stimulate NBNT cells to produce IL‐4 and induce the switch of B cells to IgE synthesis. NBNT cells derived from the spleen and bone marrow of SCID mice were able to produce IL‐4 on exposure to IL‐3. This suggested that the ability of IL‐3 to stimulate IL‐4 production was not dependent on prior exposure of the NBNT cells to antibody complexes in vivo. Taken together these findings represent the first observation that enough IL‐4 is produced by NBNT cells to actually influence a B cell IgG/Ig response. The findings also clearly demonstrate that B cells do not need high concentrations of IL‐4 to be directed to switch to IgG1 and IgE synthesis.
Structural and functional epitopes of the human adhesion receptor CD58 (LFA‐3)
Authors: Dengler Thomas J. , Hoffmann Jörg C. , Knolle Percy , Albert‐Wolf Marion , Roux Matthias , Wallich Reinhard , Meuer Stefan C. 
Published: March 2007

AbstractCD58 (LFA‐3), a heavily glycosylated protein of 40–70 kDa, is expressed on a broad range of hematopoietic and non‐hematopoietic cells. It serves as a physiological ligand of the CD2 receptor, present on T cells and natural killer cells, and plays, thus, an important role in lymphocyte adhesion and T cell activation through CD2. Whereas several epitopes and their respective function are known for CD2, a similarly detailed characterization of CD58 is still lacking. We raised a panel of novel murine monoclonal antibodies (mAb) against recombinant human CD58 and describe here the identification of six structurally and/or functionally distinct epitopes on the CD58 molecule. All epitopes were found to be present in equal numbers on a wide range of CD58+ cells, none of them being differentially up‐regulated following cell activation or malignant transformation. Two of these epitopes represent functionally relevant sites, involved in binding of CD58 to CD2 and T cell activation via CD2. One further epitope appears to be selectively involved in CD58‐mediated activation, whereas the other three displayed no functional effects. The new mAb allow for the first time the detection of CD58 in enzyme‐linked immunosorbent assays and immunofluorescence while bound to its receptor CD2 in human serum or on freshly isolated blood cells. Finally, one mAb was found to specifically cross‐react with T11TS, the equivalent of CD58 in sheep.