bluuebunny/crossref_metadata_2025_split huggingface dataset:
Charge‐dependent binding of granzyme A (MTSP‐1) to basement membranes
Authors: Vettel Ulrike , Brunner Georg , Bar‐Shavit Rachel , Vlodavsky Israel , Kramer Michael D. 
Published: March 2007

AbstractThe murine T cell‐associated serine proteinase granzyme A [also termed Murine Tcell‐associated serine proteinase‐1 (MTSP‐1), or SE‐1] expresses optimal enzymatic activity under extracellular milieu conditions. It degrades a variety of proteins that are constituents of basement membranes. Granzyme A is harbored within intracellular storage granules from which its release can be induced by appropriate ligand binding to extracellular matrix receptors of Tcells. Secreted granzyme A has, therefore, been implicated in the degradation of extracellular matrix barriers during T cell migration. Here we show that granzyme A binds to natural basement membranes in a charge‐dependent manner. Binding of granzyme A to charged surfaces protects it from inhibition by natural high molecular weight inhibitors. The interaction of granzyme A with in vitro‐produced extracellular matrices liberates basic fibroblast growth factor, which is bound to negatively charged heparan sulfate glycosaminoglycans of the extracellular matrix. We propose that the charge‐dependent interaction of granzyme A with basement membranes has multiple, biologically relevant consequences.
Co‐selection of the rare T cell receptor‐γ B haplotype in mouse lines selected for low responsiveness to red blood cell antigens
Authors: Roger Thierry , Pépin Louis‐Ferdinand , Couderc Jacques , de Franco Marcelo , Seman Michel 
Published: March 2007

AbstractTcell receptor (TcR)‐γ haplotype was investigated in seven pairs of murine Biozzi lines selected for low and high antibody (Ab) response to different antigens (Ag). High‐responder lines (H) express γA or γC haplotypes irrespective of the selecting Ag. In contrast, the γB haplotype, which is rare in laboratory mouse strains, is found in all Iow‐responder lines (L) to sheep erythrocyte Ag (SE). However, the TcR‐γB locus might only have a low penetrance in the control of the SE response. Moreover, investigations using LIVA mice, which were selected for low SE response from homozygous γA founder parents, indicate that the γB haplotype is neither necessary nor sufficient to achieve a low‐responder phenotype. The γB haplotype might, thus, be co‐selected to confer to L mice an improved resistance to bacterial infections mediated by γδ5 T cells compensating the profound and nonspecific immune perturbation associated with the low Ab response.
B7/BB1, the ligand for CD28, is expressed on repeatedly activated human T cells in vitro
Authors: Sansom David M. , Hall Nicolas D. 
Published: March 2007

AbstractThe activation of T cells is now thought to require at least two distinct signals. One signal is delivered through the interaction of the antigen‐specific T cell receptor with major histocompatibility complex (MHC) molecules and peptide, while the other is received from interactions with less precisely defined accessory or costimulatory molecules. In the absence of this second costimulatory signal, some T cells subsequently become unresponsive to antigenic stimulation. One of the major candidates for providing such a second signal to T cells is the molecule B7 interacting with the T cell glycoprotein CD28. In the present study we have investigated whether B7 is expressed on human T cell lines and clones, since these cells have the capacity to present antigen to each other by expressing MHC class II molecules. Our results demonstrate that B7 can be detected on T cell clones and on repeatedly activated but not freshly isolated peripheral blood T cells. The expression of B7 is dependent on the state of activation of the cells, being maximally expressed shortly after restimulation and becoming undetectable as the cells quiesce. Together, these results suggest that B7 expression may be of importance to T cells, perhaps in the avoidance of anergy.
Improved survival from potentially lethal graft‐vs.‐host disease by donor pretreatment with a recipient‐specific blood transfusion. II. Evidence for a principal role of the CD4+ T cell subset
Authors: Knulst Andre C. , Tibbe G. John M. , Bril‐Bazuin Clara , Benner Robbert 
Published: March 2007

AbstractPretreatment of prospective donors of hemopoietic cells with a single recipient‐specific blood transfusion can significantly decrease the morbidity and mortality of potentially lethal graft‐vs.‐host disease (GVHD) in lethally irradiated, allogeneically reconstituted mice. In a previous report we described the requirements for induction of this blood transfusion effect. In the present study we addressed in particular the mechanism underlying this effect. The beneficial effect of blood transfusion appeared to be due to the white blood cell population in the transfused blood. X‐irradiation (20 Gy) of the blood prior to transfusion did not abrogate the effect, which makes a veto cell mechanism unlikely. The blood transfusion effect in this model appeared to be mediated by the CD4+ T cell subset, since purified CD4+ spleen cells from transfused donors caused considerably less morbidity and mortality than naive CD4+ spleen cells. Apparently CD8+ cells were not involved, because their absence did not affect the beneficial effect. This observation was further confirmed by the finding that treatment of recipient mice that were reconstituted with spleen cells from transfused donors with anti‐CD8 monoclonal antibody (mAb) did not abrogate the blood transfusion effect. Interestingly, the blood transfusion effect was enhanced by administration of anti‐CD4 mAb to the recipients. The anti‐CD4 mAb might impair the interaction between T cells and antigen‐presenting cells, resulting in functional inactivation.
NK1.1+ CD4+ CD8‐ thymocytes with specific lymphokine secretion
Authors: Arase Hisashi , Arase Noriko , Nakagawa Ken‐Ichi , Good Robert A. , Onoé Kazunori 
Published: March 2007

AbstractCD4+8− or CD4−8+ thymocytes have been regarded as direct progenitors of peripheral T cells. However, recently, we have found a novel NK1.1+ subpopulation with skewed T cell antigen receptor (TcR) Vβ family among heat‐stable antigen negative (HSA−) CD4+8− thymocytes. In the present study, we show that these NK1.1+ CD4+8− thymocytes, which represent a different lineage from the major NK1.1− CD4+8− thymocytes or CD4+ lymph node T cells, vigorously secrete interleukin (IL)‐4 and interfron (IFN)‐γ upon stimulation with immobilized anti‐TcR‐αβ antibody. On the other hand, neither NK1.1− CD4+8−thymocytes nor CD4+ lymph node T cells produced substantial amounts of these lymphokines. A similar pattern of lymphokine secretion was observed with the NK1.1+ CD4+ T cells obtained from bone marrow. The present findings elucidate the recent observations that HSA− CD4+8− thymocytes secrete a variety of lymphokines including IFN‐γ, IL‐4, IL‐5 and IL‐10 before the CD4+8− thymocytes are exported from thymus. Our evidence indicates that NK1.1+ CD4+8− thymocytes are totally responsible for the specific lymphokine secretions observed in the HSA‐ CD4+8− thymocytes.
Intestinal T lymphocytes in the chicken express an integrin‐like antigen
Authors: Haury Matthias , Kasahara Yoshihito , Schaal Stefan , Bucy R. Pat , Cooper Max D. 
Published: March 2007

AbstractWe report the characterization of a molecule recognized on chicken T cells by the murine A19 monoclonal antibody that was generated by immunization with intestinal intraepithelial lymphocytes. Immunofluorescence analysis indicated that both αβ and γδ T cell subpopulations in the intestine express the A19 antigen, but natural killer cells and B cells do not. The A19‐marked T cells were preferentially localized in the intestinal epithelium and less frequently in the underlying lamina proprial, T cells appearing in the intestine during embryonic life were A19 negative but acquired the antigen within the first few days after hatching. Although rarely found on cells in non‐intestinal tissues at any age, very late expression of the A19 antigen could be induced by concanavalin A stimulation of splenic and circulating T cells. Transforming growth factor β1 enhanced this induction of A19 expression. The A19 molecules expressed by intestinal T cells and activated splenic T cells were biochemically identical, consisting of a multi‐molecular complex of proteins with approximate Mr of 205, 145 and 75 kDa under nonreducing conditions and 120, 90 and 28 kDa under reducing conditions. The characteristics of this multimolecular complex and its differential expression suggest that the A19 antigen is a member of the integrin family which may function in the retention of intestinal lymphocytes.
Transcriptional diversity at the duplicated human CD8β loci
Authors: Disanto James P. , Smith Deborah , De Bruin Derik , Lacy Elizabeth , Flomenberg Neal 
Published: March 2007

AbstractIn order to understand the structural organization of the human CD8β locus, genomic clones containing CD8β sequences were isolated and analyzed. Physical linkage of these clones with the CD8α locus using pulsed‐field electrophoresis revealed a duplication of the CD8β locus. CD8B‐1 lies 35 kb upstream from the CD8α locus and contains eight exons, including four alternatively spliced cytoplasmic exons. The CD8B‐2 gene contains six exons and is at present unlinked to CD8B‐1. Analysis of sequences upstream to the leader exon of the CD8B‐1 and CD8B‐2 genes revealed a GC‐rich promoter which lacks canonical “CCAAT” and “TATA” motifs, but which has sites for multiple transcriptional activators and three additional elements which are conserved in the murine CD8β promoter. Seven unique CD8β cDNA isoforms were isolated and characterized, which derive from alternative splicing of the transmembrane and/or cytoplasmic exons. Three cDNA are membrane spanning, while the remaining four isoforms lack a transmembrane region and are potentially secreted. These transcripts are differentially expressed in the thymus and in the periphery. Transaction experiments in murine fibroblasts confirmed that the membrane CD8β isoforms could be expressed as heterodimers with the CD8α chain. The regulated expression of multiple CD8β cytoplasmic isoforms and their potential role in T lymphocyte signal transduction is discussed.
Only a small proportion of splenic B cells in adults are short‐lived virgin cells
Authors: Chan Eric Y.‐T. , Maclennan Ian C. M. 
Published: March 2007

AbstractA cohort of newly produced virgin B cells was followed from the marrow to the spleen of non‐immunized clean rats, which showed minimal antigen‐driven proliferation of B cells in their spleens. The progenitors of this cohort of virgin cells were labeled in vivo over 12 h with the thymidine analogue 5‐bromo‐2′‐deoxyuridine (BrdUrd) and their non proliferating progeny left the marrow 2‐3 days later. This coincided with the arrival of labeled B cells in the red pulp and T zones of the spleen. These appear to be short‐lived as few remained a week after the label was given. The short‐lived newly produced virgin B cells can only comprise a minority of splenic B cells, for it is shown that only 20% of splenic B cells are found in the red pulp and T zone. It is calculated that newly produced virgin B cells are likely to make up between 5% and 10% of splenic B cells. In the marginal zones and follicular mantle respective medians of 3.3% and 1.8% were already labeled at 1 day from the start of the BrdUrd pulse. The appearance of these cells seems likely to result from antigen‐driven B cell proliferation outside the marrow, for labeled virgin B cells have not started to leave the marrow at this stage. During day 2 and 3 the proportion of labeled follicular mantle B cells rose to 3.4%, which might in part reflect the recruitment of newly produced virgin B cells to the pool of recirculating follicular B cells. After day 3 in the follicles and day 1 in the marginal zones the proportion of labeled cells did not vary significantly through day 7. This appears to confirm the comparative longevity of the cells in these zones, which contain 80% of the non‐proliferating splenic B cells of adult rats.
Complement‐dependent synergistic effects of rat monoclonal IgG antibodies in vivo
Authors: Yousaf Nasim , Howard Jonathan C. , Williams Bryan D. 
Published: March 2007

AbstractWe describe studies aimed at maximizing the effector mechanisms responsible for eliminating target erythrocytes from the circulation in a fully homologous opsonization system in vivo. The effects on the subsequent fate of target erythrocytes were examined in both normal and decomplemented rats preinjected with a variety of rat IgG monoclonal antibodies (mAb) directed against different epitopes on the RTlAa, the classical class I major histocompatibiliy complex antigen of the DA rat. In general, the clearance of both DA and (DA × PVG)F1 erythrocytes in normal rats preinjected with various pairs of noncompetitive mAb was very rapid when compared with the overall clearance patterns seen with individual antibodies. With all mAb combinations containing IgG2b or IgG2a, an intact complement system was an essential requirement for augmenting the initial clearance and promoting hepatic sequestration of these target cells. The removal of (DA × PVG)F1 erythrocytes, expressing half as much antigen, was considerably slower than the DA cells for each antibody pair tested although a notable degree of heterogeneity was observed in the overall behavior of both types of target cells with different mAb combinations. Our results suggest that the limiting effects of low antigen density on the target cells combined with the use of mAb of an isotype like the rat IgG2a can be overcome using pairs of mAb that recognize different epitopes on the same target antigen.
Human interleukin‐5 induces staphylococcal A Cowan 1 strain‐activated human B cells to secrete IgM
Authors: Bertolini John N. , Sanderson Colin J. , Benson Elizabeth M. 
Published: March 2007

AbstractStudies on the role of human interleukin (IL)‐5 in B cell growth and differentiation have yielded conflicting results. To clarify this issue, we studied the role of purified recombinant IL‐5 on activated human B cells which were depleted of Tcells and adherent cells. Human IL‐5 augments IgM secretion, but not IgG or IgA secretion of purified human B cells activated with staphylococcal A Cowan 1 strain (SAC). However, the period of B cell activation with SAC is critical for the B cell to respond to IL‐5. After 24 h of SAC activation, human B cells are responsive to the IL‐5 signal, but with longer periods of activation, IL‐5 responsiveness diminishes. This may explain some of the previous conflicting results. The IgM enhancement was not seen when B cells were activated with pokeweed mitogen. In addition, human recombinant IL‐4 synergized with IL‐5 in augmenting IgM secretion by SAC‐activated B cells, while IL‐5 synergized with IL‐2 to augment IgM, IgG and IgA secretion by SAC‐activated B cells. As the purified IL‐5 was derived from a COS‐1 cell supernatant, and COS‐1 cells secrete IL‐6, we examined whether a polyclonal IL‐6 antibody blocked the IgM‐enhancing activity of IL‐5. IL‐6 antibody did not block the IL‐5 enhancement of IgM secretion, but a monoclonal antibody to IL‐5 inhibited the human IL‐5 activity on human B cells. These results demonstrate that human IL‐5 augments IgM secretion of SAC‐activated human B‐cells. In addition, this lymphokine synergizes with IL‐4 and IL‐2 in supporting Ig secretion.
A sequence pattern for peptides presented to cytotoxic T lymphocytes by HLA B8 revealed by analysis of epitopes and eluted peptides
Authors: Sutton Julian , Rowland‐Jones Sarah , Rosenberg William , Nixon Douglas , Gotch Frances , Gao Xiao‐Ming , Murray Nick , Spoonas Anna , Driscoll Paul , Smith Michael , Willis Anthony , McMichael Andrew 
Published: March 2007

AbstractHLA B8‐restricted cytotoxic T lymphocytes (CTL) specific for influenza A virus were generated and shown to recognize the nucleoprotein (NP). The dominant epitope was mapped using recombinant vaccinia viruses that expressed fragments of the NP and then synthetic peptides baseds on the NP amino acid sequence. The peptide 380‐393 was first identified and further refined; it was shown that the glutamic acid at position 380 was essential for recognition by CTL and that the nonamer 380‐388 was the optimum peptide. Six HLA B8‐positive influenza immune donors that we have tested respond to this peptide as part of their influenza‐specific CTL response. The amino acid sequence of the peptide epitope was compared to six other known virus peptides known to be restricted by HLA B8 and a sequence homology was identified, which predicted nonamer and octamer epitope sequences. Probable anchor residues were identified at peptide residues 3 (lysine/arginine), 5 (lysine/arginine) and 9 (leucine/isoleucine). Support for this pattern came from sequencing peptides eluted from purified HLA B8 molecules, where lysines were predominant at positions 3 and 5. One of the predicted epitope peptides was made and shown to be recognized by specific CTL. These and the two others were shown to compete with NP 380‐388 for binding to HLA B8. A model was made of the HLA B8 molecule and negatively charged pockets predicted, which could accomodate the positively charged side chains of the peptide anchor residues.
Covalent binding of guanine nucleotides to the CD3‐γ chain of the T cell receptor/CD3 complex
Authors: Peter Marcus E. , Wileman Thomas , Terhorst Cox 
Published: March 2007

AbstractIn a search for proteins involved in signal transduction through the T cell receptor (TcR/CD3 complex), a recently developed highly efficient method for labeling of nucleotide binding proteins in permeabilized cells was applied. Here, we report that human CD3‐γ could be labeled by periodate‐oxidized [α‐32P] GTP (GTPoxi). In contrast to GTPoxi labeling of CD3‐ξ, (Peter, M. E., Hall, C, Ruhlmann, A., Sancho, J. and Terhorst, C, EMBOJ. 1992. 11: 933), GTP‐specific labeling of CD3‐γ reached a maximum when nucleotides were added 60 min prior to the cross‐linking reaction. As CD3‐γ did not contain a known consensus sequence for nucleotide binding and since labeling kinetics of CD3‐γ coincided with those of cytosolic GTP‐binding proteins, labeling may have been caused by a GTP‐binding protein. This putative protein was not T cell specific because labeling of CD3‐γ could also be achieved when expressed in the endoplasmic reticulum of Chinese hamster ovary (CHO) cells. In CHO cells, labeling by GTPoxi took place only when CD3‐γ was associated with CD3‐ξ, whereas labeling could not be established upon association of CD3‐γ with CD3‐δ or TcR α. The observation that CD3‐γ was labeled without leaving the endoplasmic reticulum led to the hypothesis that the association of CD3‐γ with a GTP‐binding protein might be involved in an early step of the TcR/CD3 complex formation or transport.
The soluble interleukin‐6 receptor is generated by shedding
Authors: Mülberg Jürgen , Schooltink Heidi , Stoyan Tanja , Günther Monika , Graeve Lutz , Buse Gerhard , Mackiewicz Andrzej , Heinrich Peter C. , Rose‐John Stefan 
Published: March 2007

AbstractThe ligand‐binding subunit (gp80) of the human interleukin‐6 receptor (IL‐6R) was transiently expressed in COS‐7 cells. The metabolically labeled protein was shown to be quantitatively released from the membrane within 20 h. We identified the protein released from the transfected COS‐7 cells after purification to homogeneity and N‐terminal sequencing as a soluble form of the gp80/IL‐6R. Shedding of the gp80 protein was strongly induced by 4β‐phorbol‐12‐myristate‐13‐acetate, indicating that the process was regulated by protein kinase C (PKC). This was further corroborated by the finding that co‐transfection of a PKC expression plasmid led to enhanced shedding of the gp80 protein. Since shedding of gp80 could not be prevented by treatment of the cells with inhibitors of all known classes of proteases, a novel protease seems to be involved. As a control, an unrelated membrane protein (vesicular stomatitis virus glycoprotein) was transfected into COS‐7 cells and analyzed for shedding. Since the turnover of this protein was not mediated by shedding, we conclude that the release of gp80 from COS‐7 cells is a specific process. The shed gp80 protein specifically binds IL‐6, and this complex shows biological activity on human hepatoma cells. Human peripheral blood monocytes released a soluble form of the gp80 protein into the culture medium upon PMA treatment indicating that PKC‐regulated shedding is the physiological mechanism of generation of the soluble IL‐6R.
Evidence for a human IgG1 class switch program
Authors: Irsch Johannes , Hendriks Rudolf , Tesch Hans , Schuurman Ruud , Radbruch Andreas 
Published: March 2007

AbstractIn activated murine B lymphocytes, immunoglobulin class switch recombination occurs as a highly regulated process which is targeted to distinct switch regions. Here we present first evidence that in human B lymphocytes, switch recombination is targeted to distinct switch regions as well. In a panel of clonally unrelated IgG1‐expressing human B cells, immortalized by Epstein‐Barr virus (EBV) transformation, seven out of nine cells show switch recombination between Sμ and Sγ1 on both alleles, the active and inactive one. The remaining cells show no switch recombination on the inactive IgH locus. The very strong correlation of switch recombination on both alleles of IgG1‐expressing cells proves that class switch recombination to IgG1 is not random but directed in human B lymphocytes.
Diverse T cell receptor β chain usage by rat encephalitogenic T cells reactive to residues 68‐88 of myelin basic protein
Authors: Sun Deming , Le Junyi , Coleclough Christopher 
Published: March 2007

AbstractEncephalitogenic T cells not only cause experimental autoimmune encephalomyelitis (EAE), but they induce resistance against subsequent induction of the disease as well. The T cell receptor (TcR) of encephalitogenic T cells is believed to contribute to their vaccinating activity. Findings in support of this assumption include the apparent restricted use of particular TcR elements, such as Vβ8.2. However, results from other laboratories including ours do not support this idea. We previously showed that rat T cells reactive against the conserved encephalitogenic epitope of myelin basic protein [MBP (87‐99)] use the TcR in a heterogeneous fashion (Sun, D. et al., Eur. J. Immunol. 1992. 22: 591). Here we show, in Lewis rats, that the TcR β chain usage of T cells specific for the dominant MBP (68‐88) epitope is not restricted to Vβ8.2. Not only did such cells rely on diverse Vβ chains, but some non‐Vβ8‐bearing cells were highly encephalitogenic. We also show that antigen‐presenting cells (APC) play an important role in determining the TcR usage of MBP‐specific T cells. Stimulation of MBP (68‐88)‐specific T cell lines by cloned APC derived from different sources resulted in selection of encephalitogenic T cells bearing different TcR β chains.