bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of the development of immediate hypersensitivity by staphylococcal enterotoxin B
Authors: Saloga Joachim , Lack Gideon , Bradley Kathrine , Renz Harald , Larsen Gary , Leung Donald Y. M. , Gelfand Erwin W. 
Published: March 2007

AbstractWe investigated the ability of staphylococcal enterotoxin B (SEB) to modify the immediate hypersensitivity response induced in BALB/c mice following sensitization to ovalbumin (OVA), a response mediated by OVA‐reactive Vβ8 T cells. Mice were sensitized by skin painting with OVA every second day over a period of 2 weeks. SEB, a potent activator of Vβ8+ T cells, was administered at the same site where OVA was applied (skin of the lower abdomen) following two different protocols. In protocol (A) SEB was injected intradermally 1 day before painting with OVA and on day 7; in protocol B, SEB was injected each time OVA was applied to the skin (eight times). SEB (but not SEA) altered the development of immediate hypersensitivity to OVA, as demonstrated by the reduction in allergen‐specific IgE, decreased OVA‐specific immediate skin test responsiveness, and prevented the development of increased airways responsiveness after bronchial challenge with OVA. Injections of SEB did not alter the proliferative responses of local draining lymph node cells or spleen mononuclear cells to OVA, indicating that administration of SEB did not inhibit the sensitization to OVA, but shifted the immune response away from an immediate type response (IgE/IgG1) to IgG2a, IgG2b and IgG3. Although both protocols of SEB treatment did not lead to a major deletion of the Vβ8 T cell population, they did reduce the proliferative response of Vβ8+ T cells to OVA. These data indicate that the bacterial toxin SEB is capable of modifying the immediate hypersensitivity response induced by OVA by altering the functional capacity of antigen‐reactive Vβ8 T cells.
On the various manifestations of spontaneous autoimmune diabetes in rodent models
Authors: Degermann Sylvie , Reilly Christina , Scott Bernadette , Ogata Lynn , Boehmer Harald Von , Lo David 
Published: March 2007

AbstractAutoimmune (type 1) diabetes mellitus in mouse, rat, and humans shares several features, including T lymphocyte infiltration into pancreatic islets and a dependence on permissive class II major histocompatibility complex (MHC) alleles. We report here on an experimental model involving mice that express influenza hemagglutinin (HA) under the control of the insulin promoter and, at the same time, a transgenic class II MHC‐restricted T cell receptor (TcR) specific for an HA peptide. These mice spontaneously develop islet infiltrates resembling those found in NOD mice and most animals become diabetic within 8 weeks of age. Because of the availability of a clonotypic TcR antibody, we can be confident that the Ins‐HA transgene does not induce any measurable alterations in the vast majority of T cells with the transgenic TcR in primary and secondary lymphoid organs. Continuous export of large numbers of HA‐specific lymphocytes from the thymus was not required for the manifestation of the disease since mice thymectomized at 3 days after birth still developed the disease albeit with smaller infiltrates.
Elongated peptides, not the predicted nonapeptide stimulate a major histocompatibility complex class I‐restricted cytotoxic T lymphocyte clone with specificity for a bacterial heat shock protein
Authors: Schoel Bernd , Zügel Ulrich , Ruppert Thomas , Kaufmann Stefan H. E. 
Published: March 2007

AbstractThe peptides recognized by an H‐2Db‐restricted CD8 cytotoxic T lymphocyte (CTL) clone which is specific for the 60‐kDa mycobacterial heat shock protein (hsp) and cross‐reacts with stressed host cells were characterized. None of the nonapeptides from hsp60 conforming to the H‐2Db binding motif were able to sensitize target cells for lysis by this CTL clone. Sequence analysis of the stimulatory fraction from a trypsin digest of hsp60, together with synthetic peptide studies, defined a cluster of overlapping epitopes. Carboxy‐terminal extension by at least one amino acid of the nonamer predicted to bind best to H‐2Db was essential for CTL recognition. Two such elongated peptides, a 10‐mer and a 12‐mer stimulated the clone at similarly low concentrations in the 100 pM range. We assume that these two peptides comply best with the natural epitope. In contrast, the 11‐mer was inactive. The stimulatory 10‐mer bound to H‐2Db with an efficacy similar to that of the nonapeptide corresponding to the H‐2Db motif, as revealed by peptide induced major histocompatibility complex (MHC) surface expression on RMA‐S cells and competitive blocking of epitope recognition by the nonamer. Binding of these carboxy‐terminally extended peptides to the MHC groove can be explained by anchoring through the amino acid residue Asn in position 5 of the peptide and by intrusion of the hydrophobic carboxy‐terminal Ala (10‐mer) or Leu (12‐mer), but not Gly (11‐mer), into the hydrophobic pocket of the H‐2Db cleft. Because the carboxy‐terminal part is thus larger than predicted this region of the peptide may arch up from the binding groove. We assume that recognition of steric components of the MHC/peptide complex broaden the range of epitope specificity for a single T cell receptor. This flexibility not only promotes recognition of several overlapping peptides from a single antigen, but may also increase the chance of cross‐reaction with similar peptides from unrelated proteins, including autoantigens. Consistent with this latter assumption, the T cell clone cross‐recognizes mycobacterial hsp60 and stressed host cells.
Expression and regulation of adhesion molecules by γδ T cells from lymphoid tissues and intestinal epithelium
Authors: Chao Cheng‐Chi , Sandor Matyas , Dailey Morris O. 
Published: March 2007

AbstractT cells bearing the γδ T cell receptor localize largely in epithelial tissues, but are also present at low frequency in organized secondary lymphoid organs. To assess the role of cell surface adhesion molecules in the traffic and tissue localization of γδ T cells, we compared the expression of these molecules on both αβ and γδ T cells in several lymphoid and non‐lymphoid organs. In the gut epithelium, γδ cells express less LFA‐1 (CD11a), Pgp‐1 (CD44), and α4 integrin than the corresponding αβ cells. In lymph nodes (LN) and Peyer's patches (PP), adhesion molecule expression by γδ cells is heterogeneous, with some of the cells having a phenotype similar to that of intraepithelial γδ cells and the rest expressing high levels of CD44 and L‐selectin (CD62L) but lower β7 and αM290, a phenotype more like lymph node αβ cells. Therefore, the particular set of adhesion molecules expressed by a T cell is dependent, in part, on its anatomic location. Superimposed upon this, however, are differences in expression that are based on the type of T cell; LN and PP γδ T cells express less CD44 but much more β7, αM290 and ICAM‐1 (CD54) than αβ T cells in the same organ. The differences in adhesion molecules between αβ and γδ cells are not due simply to differences in their activation status, because these molecules are regulated differently after activation through the T cell receptor (TcR)/CD3 complex. The differential expression of adhesion molecules on cells bearing a particular TcR V region suggests that distinct adhesion phenotypes may arise from prior contact with specific antigen and resultant cell activation in vivo. Lastly, the presence of high level expression of α4β7 and αM290 on L‐selectinlo γδ cells in lymph nodes suggests that these γδ cells may be uniquely capable of migrating to the gut. The differences in adhesion molecule expression and regulation between γδ and αβ T cells could explain, in part, the distinct homing and tissue localization of these T cell subsets in vivo.
Induction by transforming growth factor‐β1 of the interleukin‐1 receptor antagonist and of its intracellular form in human polymorphonuclear cells
Authors: Muzio Marta , Sironi Marina , Polentarutti Nadia , Mantovani Alberto , Colotta Francesco 
Published: March 2007

AbstractThe aim of this study was to examine the expression of interleukin‐1 receptor antagonist (IL‐1ra) in human polymorphonuclear cells (PMN) treated with transforming growth factor‐β1 (TGFβ1). TGFβ1 induced IL‐1ra transcripts in human circulating PMN and the induction was not blocked by protein synthesis inhibitors. Actinomycin D blocked induction by TGFβ1 of IL‐1ra transcripts, suggesting the involvement of gene transcription. The half life of IL‐1ra transcripts was prolonged by TGFβ1. By reverse transcriptase‐polymerase chain reaction, TGFβ1 was found to augment the transcripts coding for both the intracellular (keratinocyte type) and the secreted form of IL‐1ra. TGFβ1 induced the production of IL‐1ra in PMN. Induction of IL‐1ra by TGFβ1 in PMN may represent a further mechanism by which this molecule can counteract the potent pro‐inflammatory properties of IL‐1.
Functional and molecular characterization of B cell‐responsive Vδ1+ γδ T cells
Authors: Orsini Daniela L. M. , van Gils Mariëlle , Kooy Yvonne M. C. , Struyk Linda , Klein George , Elsen Peter Van Den , Koning Frits 
Published: March 2007

AbstractCells expressing the Vδ1+ gene segment are a minor γδ T cell population in human peripheral blood but predominate in epithelia and (inflamed) tissues. The characteristic dendritic‐like morphology of these γδ T cells is consistent with their putative immune surveillance role in epithelia. Their function, however, remains unknown. We and others previously reported that a subset of Vδ1+ γδ T cells proliferates after stimulation with Epstein‐Barr virus (EBV)‐transformed B lymphoblastoid cell lines (LCL), but not with fresh peripheral blood‐derived B cells. These responses were independent of the type of T cell receptor (TcR) γ chain co‐expressed with the Vδ1 chain. The in vivo relevance of this LCL‐mediated activation as well as the nature of the stimulatory ligand on the LCL is not well established. In this study, we tested the proliferative response of Vδ1+ LCL‐responsive T cells against non‐EBV‐transformed B cells, activated through CD40 by murine EL4 B5 cells, and to a panel of B cell lines differing in the expression of EBV nuclear antigen proteins and adhesion/co‐stimulatory molecules. The role of the Epstein‐Barr virus‐derived antigen in the induction of this response could be excluded as the activated (non‐EBV‐transformed) peripheral blood B cells were also able to induce a proliferative response in the LCL‐responsive Vδ1+ T cells. Therefore, the stimulatory ligand on B cells is of cellular rather than of viral origin, and its expression is up‐regulated upon activation of B cells. The expression of B7 and CD39 molecules on the surface of activated B cells appeared to be crucial since antibodies to these structures could block the induction of proliferation of the Vδ1+ T cells. Finally, we investigated the diversity of the responding Vδ1+ γδ T cell clones by sequence analysis of the TcRδ junctional regions. No restricted V‐D‐J sequences were found among the LCL‐responsive Vδ1+ T cell clones, arguing strongly against a mono‐ or oligoclonal Vδ1+ γδ T cell response to LCL. These findings may explain the presence of polyclonally activated Vδ1+ T cells in inflamed tissues where activated B cells are often present.
Detachment and cytolysis of human endothelial cells by proteinase 3
Authors: Ballieux Bart E. P. B. , Hiemstra Pieter S. , Klar‐Mohamad Ngaisah , Hagen E. Christiaan , van Es Leendert A. , van der Woude Fokko J. , Daha Mohamed R. 
Published: March 2007

AbstractActivation and degranulation of polymorphonuclear leukocytes (PMN) with release of proteolytic enzymes, such as proteinase 3 (PR3) and elastase, in the vessels of patients with Wegener's granulomatosis (WG) is thought to play an important role in the vascular endothelial cell damage. We have investigated the detachment and cytolysis of 51Cr‐labeled umbilical vein endothelial cells (HUVEC) induced by highly purified, enzymatically active, PR3 and elastase. Incubation of confluent monolayers of HUVEC with 100 mU/ml of PR3 for 3 h at 37°C generally resulted in 20% detachment and 30% cytolysis. Elastase (350 mU/ml) induced approximately 40% detachment and 15% cytolysis. Both PR3‐mediated and elastase‐mediated detachment and cytolysis were fully inhibited by alpha‐1‐proteinase inhibitor (α1PI), while anti‐leukoprotease (ALP) only inhibited elastase‐mediated endothelial damage. By selective inhibition of an azurophilic granule extract with either α1PI or ALP we calculated that PR3 is responsible for 23% of the total detachment and cytolysis induced by the extract. Elastase was responsible for 60% of the detachment and 19% of the cytolysis. Detachment induced by PR3 was inhibited by three out of five IgG preparations purified from c‐ANCA‐positive sera of WG patients. PR3‐mediated cytolysis was inhibited by each of the c‐ANCA + IgG preparations and also to a limited extent by control IgG, suggesting a partial nonspecific stabilization of the endothelial cells. These studies provide evidence that besides elastase, PR3 also plays an important role in the PMN‐mediated endothelial cell damage.
Interleukin‐4 but not interleukin‐10 inhibits the production of leukemia inhibitory factor by rheumatoid synovium and synoviocytes
Authors: Dechanet Julie , Taupin Jean‐Luc , Chomarat Pascale , Rissoan Marie‐Clotilde , Moreau Jean‐François , Banchereau Jacques , Miossec Pierre 
Published: March 2007

AbstractThe expression of the proinflammatory cytokine leukemia inhibitory factor (LIF) has been reported in the cartilage and synovium of rheumatoid arthritis (RA) patients. Here, we show that high levels of LIF were constitutively produced by cultures of synovium pieces. Low levels of LIF were produced spontaneously by isolated synoviocytes, but interleukin (IL)‐1β caused a fourfold enhancement of this secretion. The anti‐inflammatory cytokine IL‐4 reduced the production of LIF by synovium pieces by 75%, as observed earlier with IL‐6, IL‐1β and tumor necrosis factor (TNF)‐α. IL‐4 had a direct effect since it inhibited LIF production by unstimulated and IL‐1β‐ or TNF‐α‐stimulated synoviocytes. Conversely, IL‐4 enhanced the production of IL‐6, which shares with LIF biological activities and receptor components. The inhibitory effect of IL‐4 was dose dependent and was reversed using a blocking anti‐IL‐4 receptor antibody. Similar inhibitory action of IL‐4 on LIF production was observed on synovium pieces from patients with osteoarthritis and on normal synoviocytes. IL‐10, another anti‐inflammatory cytokine acting on monocytes, had no effect on LIF production by either synovium pieces or isolated synoviocytes. Thus, the production of LIF by synovium tissue was inhibited by IL‐4 through both a direct effect on synoviocytes and an indirect effect by inhibition of the production of LIF‐inducing cytokines.
Induction of natural killer cell migration by monocyte chemotactic protein−1, −2 and −3
Authors: Allavena Paola , Bianchi Giancarlo , Zhou Dan , Van Damme Jo , Jílek Petr , Sozzani Silvano , Mantovani Alberto 
Published: March 2007

AbstractUnder certain physiological and pathological conditions, naturall killer (NK) cells rapidly accumulate in tissues. Chemokines are an essential component of the current paradigm of leukocyte recruitment. The present study was designed to investigate the responsiveness of NK cells to the prototypic C‐C chemokine, monocyte chemotactic protein‐1 (MCP‐1). MCP‐1 induced migration across filters of interleukin (IL)‐2‐activated NK cells, whereas it was a weak attractant for unstimulated cells. Maximal induction of migration required a positive concentration gradient between the lower and the upper compartment of the chemotaxis chamber. Preliminary characterization of the MCP‐1 receptor on NK cells indicated that the chemotactic response to MCP‐1 was blocked by pre‐treatment of cells with Bordetella pertussis toxin, and MCP‐1 but not IL‐8 displaced 125I‐labeled MCP‐1 from IL‐2‐activated NK cells.The related chemokines MCP‐2 and MCP‐3 were also active – though less potent – attractants for activated NK cells. Thus the spectrum of action of MCP‐1, ‐2 and ‐3 encompasses NK cells and chemokines are likely to play a role in regulating extravasation of these cells.
T cell receptor and peptide‐contacting residues in the HLA‐DR17(3) β1 chain
Authors: Geluk Annemieke , Fu Xin‐Ting , van Meijgaarden Krista E. , Jansen Yanourishka Y. R. , de Vries René R. P. , Karr Robert W. , Ottenhoff Tom H. M. 
Published: March 2007

AbstractPreviously, we have proposed that the β1 residues 9–13, 26, 28 and 86 in HLA‐DR17, the most common subtype of DR3, might be critical for the binding of an immunodominant, mycobacterial epitope (peptide 3–13 of the 65‐kDa heat shock protein). In order to examine directly (i) which DR17 residues are involved in peptide binding, (ii) whether the same or other DR17 residues are involved in the binding of different peptides, and (iii) whether subtle differences in the mode of peptide binding can influence T cell stimulation, we have now systematically mutated 15 highly polymorphic DR17β1 residues, located in the proposed peptide binding groove of DR17, and examined the effect thereof on binding and presentation of two peptides, hsp65 p3–13 and p56–65 of the 30/31‐kDa secreted mycobacterial protein. Mutations in residues 28 (D → H) and 86 (V → G) completely eliminated binding of p3–13 and significantly reduced binding of p56–65. A mutation in residue 26 (Y → F) decreased binding of p3–13 but did not affect binding of p56–65. Substitutions of amino acid residues 28, 67, 71 and 86 in the DR17β1 chain abrogated peptide‐specific stimulation of both the p3–13‐ and the p56–65‐specific T cell clones, while specific stimulation by only one peptide was eliminated by substitution at positions 26 and 74 (p3–13) and by substitution of residues 11 and 37 (p56–65). The observation that substitution of several other peptide‐contacting DR17β1 chain residues does not significantly affect peptide binding but does affect T cell stimulation, suggests that these substitutions alter the conformation of the bound peptide.
Experimental therapy of systemic lupus erythematosus: the treatment of NZB/W mice with mouse soluble interferon‐γ receptor inhibits the onset of glomerulonephritis
Authors: Ozmen Laurence , Roman Danièle , Fountoulakis Michael , Schmid Georges , Ryffel Bernhard , Garotta Gianni 
Published: March 2007

AbstractFemale NZB/W F1 mice develop an autoimmune disease similar to human systemic lupus erythematosus (SLE), and ultimately die of glomerulonephritis. Starting at the age of 16 weeks NZB/W F1 mice were treated for a period of 19 weeks with soluble interferon‐γ receptor (sIFN‐γR), anti‐IFN‐γ monoclonal antibody (mAb) or IFN‐γ. All mice treated with sIFN‐γR or anti‐IFN‐γ mAb were alive 4 weeks after the treatment was discontinued, whereas 50% of mice died in the placebo groups and 78% of the mice died in the IFN‐γ‐treated group. Histologically, there was severe membrano‐proliferative glomerulonephritis in IFN‐γ‐ and placebo‐treated mice, and minimal or no mesangioproliferative disease in mice receiving sIFN‐γR or anti‐IFN‐γ mAb. The renal mononuclear infiltrate (T lymphocytes and monocytes), expression of major histocompatibility complex class II antigen and glomerular immunoglobulin and complement deposition were reduced in those mice. These data suggest that an IFN‐γ inhibitor, such as the soluble IFN‐γR, can be used for SLE therapy in the early stages of the disease.
Regulation of non‐classical protein kinase C isoenzymes in a human T cell line
Authors: Keenan Carolyn , Kelleher Dermot , Long Aideen 
Published: March 2007

AbstractWe have examined the expression and responses to activation, of novel/atypical protein kinase C (PKC) isoforms ε,ζ, and δ in the T cell lymphoma cell line K‐4. The effects of 1‐h phorbol 12‐myristate 13‐acetate (PMA) and OKT3 activation of K‐4 cells on PKC isoform distribution were examined. In addition, the effects of PMA‐mediated down‐regulation on the expression of PKC ε and ζ were determined using high concentrations of PMA over 24‐ and 48‐h time periods in these cells. PKC ε expression was not altered by incubation of K‐4 cells with up to 200 ng/ml PMA over a 24‐ or 48‐h period. PKC ε was down‐regulated in a concentration‐dependent manner by PMA after both 24‐ and 48‐h of activation. Expression of PKC ε was not completely depressed, however, even at the highest concentration of the phorbol ester after 48‐h incubation with PMA. The presence of PKC ε, ζ, and δ was confirmed by immunohistochemistry with distinct patterns of expression observed. PMA‐induced PKC activation for a 1‐h period resulted in a translocation of PKC δ from resting cytoplasmic/nuclear staining to a cytoplasmic aggregate. Following 1‐h activation through the T cell receptor‐associated complex CD3, PKC δ translocated from a peri‐nuclear/cytoplasmic compartment to a putative cytoskeletal location in K‐4 cells. This translocation was time dependent and redistributed to a cytoplasmic aggregate prior to the cytoskeleton. Similarily, following 1‐h activation through the T cell receptor, PKC ζ redistributed directly to what is possibly a cytoskeletal cell compartment. The cytoplasmic distribution of PKC ζ was unaltered following activation with PMA over a 1‐h time period. There was no apparent redistribution of PKC ε cytoplasmic staining pattern following a 1‐h direct or indirect activation. These results underline the differences in individual PKC isoform distribution, and responses to different stimuli, thereby providing additional evidence for the use of discrete PKC isoform signaling pathways in T cells. Furthermore, this data underlines the differences in PMA‐mediated PKC activation and activation through the T cell receptor.
Actions of the chemotactic cytokines MCP‐1, MCP‐2, MCP‐3, RANTES, MIP‐1α and MIP‐1β on human monocytes
Authors: Uguccioni Mariagrazia , D'Apuzzo Massimo , Loetscher Marcel , Dewald Beatrice , Baggiolini Marco 
Published: March 2007

AbstractThe activities of six synthetic CC chemokines, MCP‐1, MCP‐2, MCP‐3, RANTES, MIP‐1α and MIP‐1β on human blood monocytes were studied. All CC chemokines elicited a bimodal migration response in vitro. Highest numbers of migrating cells were obtained with the monocyte chemotactic proteins (MCP) and RANTES, somewhat lower numbers with MIP‐1α, and only weak migration with MIP‐1β. The most potent attractants were MCP‐1 and MIP‐1α which reached maximum efficacy at 0.1 to 1 nM. All CC chemokines also induced the release of N‐acetyl‐β‐D‐glucosaminidase from cytochalasin B‐pretreated monocytes. The MCP were most effective (MCP‐1 > MCP‐3 > MCP‐2), RANTES and MIP‐1α showed moderate (1/3 of MCP‐1 activity), and MIP‐1β only minimal activity. Cytosolic free Ca2+ changes and exocytosis were used to monitor receptor desensitization. Marked cross‐desensitization was observed among MCP‐1, MCP‐2 and MCP‐3 on the one hand, and RANTES, MIP‐1α and MIP‐1β on the other, indicating receptor sharing within these two subgroups of CC chemokines. The responses to RANTES, MIP‐1α and MIP‐1β were also moderately to markedly desensitized by pretreatment with MCP‐1, MCP‐2 or MCP‐3, while the responses to the MCP were virtually unaffected by pretreatment with RANTES, MIP‐1α and MIP‐1β. These results suggest that the MCP also interact with receptors recognized by RANTES, MIP‐1α and MIP‐1β, but not vice versa. Binding studies were performed with radiolabeled MCP‐1 or MIP‐1α. All MCP competed readily for labeled MCP‐1 yielding a concentration‐dependent sigmoidal displacement curve. Displacement with RANTES, MIP‐1α and MIP‐1β was observed at higher concentrations, but was not complete. Radiolabeled MIP‐1α was displaced efficiently by MIP‐1α or MIP‐1β, but only partially by RANTES. Of the MCP, only MC‐3 completely displaced MIP‐1α, while only partial displacement was observed with MCP‐1 and MCP‐2.