bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐10 inhibits IgE‐mediated nitric oxide synthase induction and cytokine synthesis in normal human keratinocytes
Authors: Bécherel Pierre‐André , Le Goff Liliane , Ktorza Sandra , Ouaaz Fateh , Mencia‐Huerta Jean‐Michel , Dugas Bernard , Debré Patrice , Mossalayi M. Djavad , Arock Michel 
Published: March 2007

AbstractHuman keratinocytes (HK) generate nitric oxide (NO) and proinflammatory mediators following activation with either IgE/anti‐IgE immune complexes or a combination of lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ). Recently, interleukin‐10 (IL‐10) has been shown to down‐regulate various inflammatory responses and to be secreted by lymphocytes and dendritic cells during skin inflammatory reactions. We show here that IL‐10 down‐regulates the production of tumor necrosis factor (TNF)‐α and IL‐6 by activated HK. Also, induction of inducible nitric oxide synthase (iNOS) expression in HK by IgE/anti‐IgE or LPS/IFN‐γ is significantly reduced by the addition of IL‐10. This effect is dose dependent and correlates with reduction of iNOS mRNA production and enzyme level. Therefore, IL‐10 down‐regulates NO‐mediated HK inflammatory responses and may thus participate in the regulation of the skin immune network.
Clonal deletion of major histocompatibility complex class I‐restricted CD4+CD8+ thymocytes in vitro is independent of the CD95 (APO‐1/Fas) ligand
Authors: Müller Klaus‐Peter , Mariani Sara M. , Matiba Bernd , Kyewski Bruno , Krammer Peter H. 
Published: March 2007

AbstractThe CD95 (APO‐1/Fas) ligand (CD95L) mediates apoptosis in sensitive target cells, Ca2+‐independent cytotoxicity of cells from perforin knock‐out mice, and peripheral deletion of activated T cells through engagement of its cognate receptor CD95. Double‐positive thymocytes show a high constitutive expression of CD95. Therefore, we used a model system and investigated whether negative selection through apoptosis might involve CD95/CD95L. We analyzed whether CD95L may induce antigen‐specific deletion of double‐positive thymocytes from mice transgenic for a lymphocytic choriomeningitis virus (LCMV)/H2b‐specific T cell receptor (TCR). These cells are deleted in vitro upon addition of the LCMV‐peptide 33–41 in a major histocompatibility complex‐class I‐restricted fashion. Deletion was not blocked by soluble mouse and human CD95‐Fc receptor decoys. CD95‐Fc receptor decoys, however, were effective in blocking apoptosis induced by mouse CD95L‐transfected L929 cells in sensitive CD95+ target cells and in thymocytes. These results suggest that TCR‐induced deletion of immature thymocytes in vitro is independent of CD95L. Thus, our data argue against a role of CD95L in negative selection of MHC‐class I‐restricted autoreactive thymocytes.
β2‐microglobulin with an endoplasmic reticulum retention signal increases the surface expression of folded class I major histocompatibility complex molecules
Authors: Solheim Joyce C. , Johnson Nancy A. , Carreno Beatriz M. , Lie Wen‐Rong , Hansen Ted H. 
Published: March 2007

AbstractWith β2‐microglobulin− (β2m−) cell lines such as R1E/Db, the surface expression of class I major histocompatibility complex molecules is greatly impaired, and class I molecules that are on the surface are generally misfolded. To determine whether β2m must be continually present with the class I heavy chain for the class I molecule to reach the surface in a folded conformation, a sequence encoding an endoplasmic reticulum (ER) retention signal (KDEL) was attached onto the 3′ end of a β2m cDNA. After this chimeric cDNA was transfected into R1E/Db cells, β2m‐KDEL protein was detectable by an anti‐β2m serum within the cells but not at the cell surface. Interestingly, R1E/Db cells transfected with β2m‐KDEL were found to express a high level of conformationally correct Db molecules at the cell surface. This observation implies that β2m has a critical and temporal role in the de novo folding of the class I heavy chain. We propose that the critical time for β2m association is when the class I molecule is docked with the transporter associated with antigen processing (TAP) and first interacts with peptide.
Staphylococcal enterotoxin B and tumor‐necrosis factor‐α‐induced relapses of experimental allergic encephalomyelitis: Protection by transforming growth factor‐β and interleukin‐10
Authors: Crisi Giovanna M. , Santambrogio Laura , Hochwald Gerald M. , Smith Sidney R. , Carlino Joseph A. , Thorbecke G. Jeanette 
Published: March 2007

AbstractA study was made of the ability of the superantigen staphylococcal enterotoxin B (SEB) to induce relapses of experimental allergic encephalomyelitis (EAE) in SJL mice that had partially or completely recovered from acute EAE. We find that a single injection of 0.05 mg SEB i.v. induces mild relapses in 50% of such mice. In addition, tumor necrosis factor (TNF)‐α (0.2 μg, i.p.) also induces EAE relapses in 43% of SJL mice when injected 1–2 months after recovery. SEB does not induce a second relapse if reinjected when Vβ17a+ T cells are still partially deleted. In these mice, however, TNF‐α is equally effective in inducing relapses as in mice that did not receive SEB previously. We showed earlier that transforming growth factor (TGF)‐β and TNF‐α have antagonistic effects on experimental autoimmune diseases; e.g., in spontaneously relapsing EAE, TGF‐β and anti‐TNF were protective, while anti‐TGF‐β caused disease exacerbation. Interleukin (IL)‐10 is also known to counteract certain TNF effects. We now find that both human IL‐10 and TGF‐β2 lower the incidence of EAE relapses when given simultaneously with SEB or TNF‐α. The protective effect of TGF‐β is significant only against relapses induced by SEB (reduced to 9%), and that of IL‐10 only against relapses induced by TNF (reduced to 0%) with the treatment regimens employed. Neutralizing anti‐TGF‐β does not increase the incidence of SEB‐induced EAE relapses. In contrast, anti‐IL‐10 increases both the incidence and the severity of such relapses. We conclude that TNF production is probably important in causing EAE relapses, but that other aspects of the SEB‐induced reactivation of myelin‐specific T cells also contribute. Furthermore, endogenous IL‐10 rather than TGF‐β production appears to limit the susceptibility to induction of EAE relapses in this model.
Structural and functional analysis of the promoter of the murine Vγ1.1 T cell receptor gene
Authors: Ofir Rivka , Novick Itai , Krup Margalit , Cleveland John L. , Ihle James N. , Weinstein Yacob 
Published: March 2007

AbstractThe expression of the germ‐line gene Vγ1.1‐Cγ4 of the T cell receptor (TcR) γ chain depends on interleukin (IL)‐3 induction in hematopoietic cells, while in T cells, the rearranged gene is expressed constitutively. To understand the mechanism that controls TcRγ gene expression, we cloned and characterized the structure and function of the Vγ1.1‐Cγ4TcR promoter. IL‐3‐dependent cell lines and T cell lines utilized the same transcriptional start sites. In chloramphenicol acetyltransferase (CAT) assays, the minimal 70‐bp promoter confers strong transcriptional activity which is 50–60% of the Moloney long terminal repeat promoter activity. The 500‐bp promoter region linked to the CAT gene exhibits IL‐3 dependency similar to the endogenous TcRγ gene. The immediate 3′ and 5′ flanking sequences inhibit the promoter activity two‐ to fourfold. The promoter lacks an obvious TATA box or CAAT box sequences, but contains a GC box in the untranslated region 3′ to the promoter. The GC box is the core sequence of the element which binds Sp1‐like proteins. Cloning of this Sp1 binding element in front of the thymidine kinase (TK) promoter and mutations generated in this site demonstrate its function as a silencer. Ultraviolet cross‐linking analysis with the Sp1 binding site from the TcRγ promoter revealed binding of a 90–100‐kDa protein in a T cell line (EL‐4) and 40–50 and 90–100‐kDa proteins in FDC‐P1 cells. The possible function of the Sp1‐like protein in silencing the minimal promoter activity is discussed.
Autoreactive T cells in healthy individuals show tolerance in vitro with characteristics similar to but distinct from clonal anergy
Authors: Filion Mario C. , Bradley Amanda J. , Devine Dana V. , Décary Francine , Chartrand Pierre 
Published: March 2007

AbstractPeripheral tolerance to self antigens has been suspected to play an important role in the regulation of the immune response in humans since autoreactive T cells can be isolated from the peripheral blood of healthy individuals. The mechanism of this tolerance is not known, but a number of groups have shown that autoreactive T cells can be induced to proliferate in vitro by the addition of their specific antigen and exogenous interleukin (IL)‐2. In this report, we present the analysis of autoreactive T cells, isolated from healthy individuals, to the autoantigen GpIIb‐IIIa present on circulating bone‐marrow‐derived cells and on thymic epithelial cells. We found that the response of GpIIb‐IIIa autoreactive T cells in vitro, when stimulated with GpIIb‐IIIa, shares characteristics with the response found for anergic T cells. In response to GpIIb‐IIIa, the GpIIb‐IIIa‐autoreactive T cells are neither able to proliferate nor produce IL‐2 on their own, but do express IL‐2 receptors α on their cell surface and produce IFN‐γ. This state of unresponsiveness can be broken by the addition of exogenous IL‐2 and IL‐7, as in the case of anergic T cells. However, GpIIb‐IIIa‐autoreactive T cells differ from anergic T cells in their capacity to be stimulated by IL‐12 and by their production of IL‐2 mRNA. Interestingly, once the unresponsive state to GpIIb‐IIIa has been broken by the addition of IL‐2, GpIIb‐IIIa autoreactive T cells can produce IL‐2 and proliferate when restimulated by GpIIb‐IIIa alone. Altogether, these results suggest that the tolerance of GpIIb‐IIIa autoreactive T cells from healthy individuals could involve post‐transcriptional regulation of IL‐2 expression.
Fas receptor expression on B‐lineage cells
Authors: Mandik Laura , Nguyen Kim‐Anh T. , Erikson Jan 
Published: March 2007

AbstractMice homozygous for the lpr mutation have B and T cell defects and develop autoantibodies, suggesting that lpr plays a role in their genesis. The lpr defect has been identified as a mutation in the apoptosis‐associated Fas receptor (FasR) gene. To begin to define the role of FasR in B cells, we have surveyed FasR expression on B‐lineage cells from early progenitors in the bone marrow through their maturation in the periphery. Contrary to some reports, we found that FasR is expressed on B cells at all stages of their development and is highest on germinal center B cells. FasR is not expressed on lpr/lpr‐derived cells. These data are consistent with the idea that lpr/lpr mice have an intrinsic B cell defect that may be manifested in developing as well as peripheral B cells. An unexpected finding is that B‐1 (CD5) B cells do not constitutively express FasR: FasR becomes detectable on B‐1 B cells only after activation.
Der p I, a major allergen of the house dust mite, proteolytically cleaves the low‐affinity receptor for human IgE (CD23)
Authors: Schulz Oliver , Laing Peter , Sewell Herb F. , Shakib Farouk 
Published: March 2007

AbstractThe nature of the proteases that cleave CD23 in vivo is of considerable interest, but remains unknown. Here, we demonstrate that Der p I, a major allergen of the house dust mite Dermatophagoides pteronyssinus, cleaves CD23 from the surface of cultured human B cells (RPMI 8866 B cell line). The cleavage of the receptor from the B cell surface was associated with a parallel increase in soluble CD23 (sCD23) in the culture supernatant. Furthermore, the proteolytic effect of Der p I was specific for CD23, since none of the other B cell markers tested (CD20, HLA‐DR, CD71 and CD49d) were affected. Labeled antibody experiments and protease inhibition assays clearly demonstrate that Der p I is a cysteine protease that directly cleaves a 25‐kDa fragment of CD23. These data suggest that the cysteine protease Der p I, in addition to being highly immunogenic, may up‐regulate IgE synthesis by virtue of its ability to cleave CD23.
Differential interactions between the immunoglobulin heavy chain μ intron and 3′ enhancer
Authors: Mocikat Ralph , Kardinal Christian , Klobeck Hans‐Gustav 
Published: March 2007

AbstractThe immunoglobulin heavy chain 3′ enhancer may be a novel type of a transcriptional regulation element in as much as its function is position dependent. We show that there are interactions between the μ intron and 3′ enhancer which are differentially regulated depending on the distance between the two elements. Thus, a transcriptional repression is exerted by the 3′ enhancer when juxtaposed to the intron enhancer. Whereas no or only modest synergism between the immunoglobulin μ intron and 3′ enhancer has been reported to date, we show here that the stimulatory effect is substantially increased by extending the distance between the two enhancers. In our stable expression system, the μ intron enhancer insulated the test gene from neighboring chromatin.
Relevance of residue 116 of HLA‐B27 in determining susceptibility to ankylosing spondylitis
Authors: D'amato Mauro , Fiorillo Maria Teresa , Carcassi Carlo , Mathieu Alessandro , Zuccarelli Angelo , Bitti Pier Paolo , Tosi Roberto , Sorrentino Rosa 
Published: March 2007

AbstractAnkylosing spondylitis (AS) is an autoimmune disorder strongly associated with HLA‐B27. A direct role of B27 molecules in the disease pathogenesis has been postulated, possibly by presenting to T cells an as‐yet unidentified arthritogenic peptide that triggers the autoimmune response. There are nine HLA‐B27 alleles differing from each other at one or more amino acid positions. It is important, for the identification of the arthritogenic peptide, to define which alleles, and therefore which polymorphic positions, predispose to the disease. Here, we report that HLA‐B★2709 is not associated with AS, as it was not found in patients. HLA‐B★2709 differs from the most frequent and disease‐associated HLA‐B★2705 allele for a single substitution (His vs. Asp) at position 116. Amino acid 116 is located at the bottom of the groove where the antigenic peptide sits, and it has been proven to influence the peptide‐binding specificity of HLA class I molecules. The most likely interpretation of these data is that the differences in charge and size that accompany the His‐to‐Asp substitution exclude the acceptance of the arthritogenic peptide.
Epitopes for human CD4+ cells on diphtheria toxin: Structural features of sequence segments forming epitopes recognized by most subjects
Authors: Raju Raghavanpillai , Navaneetham Duraiswamy , Okita David , Diethelm‐Okita Brenda , McCormick Daniel , Conti‐Fine Bianca M. 
Published: March 2007

AbstractThe sequence regions of diphtheria toxin (DTX) recognized by CD4+ T cells of seven healthy humans of different major histocompatibility complex haplotypes were identified. Overlapping synthetic peptides, screening the DTX sequence, were used to test in proliferation assays unselected blood CD4+ cells, or DTX‐specific CD4+ lines propagated by stimulation with DTX of blood mononuclear cells. Blood CD4+ cells and DTX‐specific CD4+ lines gave consistent results. Although each subject had an individual pattern of peptide recognition, six peptide sequences (residues 271–290, 321–340, 331–350, 351–370, 411–430 and 431–450) were recognized by all subjects. In the native DTX molecule, these sequence regions are flanked by sequence loops exposed on the DTX surface. They overlap uncharged segments of the DTX sequence. These structural properties may be general requirements for immunodominance in CD4+ cell sensitization in humans.
Raf‐1 provides a dominant but not exclusive signal for the induction of CD69 expression on T cells
Authors: Taylor‐Fishwick David A. , Siegel Jeffrey N. 
Published: March 2007

AbstractStimulation of the T cell antigen receptor (TCR) induces a number of intracellular signaling pathways which lead to the transcription of a variety of new genes. Of the newly synthesized proteins, the earliest to be detected on the cell surface is the type II integral membrane protein CD69. Cross‐linking of this activation antigen induces signaling events related to T cell activation. The proto‐oncogene product Ras has been reported to up‐regulate CD69. However, which of the potential effectors of Ras induces the expression of CD69 has remained unclear. Using transient transfection, we have shown a constitutively active form of the serine/threonine kinase Raf‐1 to be sufficient to induce CD69 expression in human Jurkat T cells. Raf‐1 was further shown to be necessary for PMA‐induced CD69 expression, since transfection of a dominant inhibitory form of Raf‐1 blocked the up‐regulation of CD69 by PMA. In addition, studies with the calcium ionophore ionomycin identified a previously uncharacterized pathway regulating the expression of CD69 in T cells. Elevation of intracellular calcium induced the expression of CD69 in both Jurkat cells and peripheral blood T cells. This effect was sensitive to the immunosuppressive drug cyclosporin A, indicating that calcium‐induced CD69 expression is mediated by the protein phosphatase calcineurin. Taken together, these results define Raf‐1 as the major signaling mediator of CD69 expression in T cells and suggest that multiple mechanisms exist to regulate the level of CD69 expression following TCR stimulation.
The roles of perforin‐ and Fas‐dependent cytotoxicity in protection against cytopathic and noncytopathic viruses
Authors: Kägi David , Seiler Peter , Pavlovic Jovan , Ledermann Birgit , Bürki Kurt , Zinkernagel Rolf M. , Hengartner Hans 
Published: March 2007

AbstractIn vitro, T cell‐dependent cytotoxicity is mediated by two distinct mechanisms, one being perforin‐, the other Fas‐dependent. The contribution of both of these mechanisms to clearance of viral infections was investigated in mice for the noncytopathic lymphocytic choriomeningitis virus (LCMV) and the cytopathic vaccinia, vesicular stomatitis (VSV) and Semliki forest (SFV) viruses. Clearance of an acute LCMV infection was mediated by the perforin‐dependent mechanism without measurable involvement of the Fas‐dependent pathway. For the resolution of vaccinia virus infection and for resistance against VSV and SFV, however, neither of the two pathways was required. These data suggest that perforin‐dependent cytotoxicity mediated by T cells is crucial for protection against noncytopathic viruses, whereas infections with cytopathic viruses are controlled by nonlytic T cell‐dependent soluble mediators such as cytokines (IFN‐γ against vaccinia virus) and neutralizing antibodies (against VSV and SFV).
Peptide anchor residue glycosylation: effect on class I major histocompatibility complex binding and cytotoxic T lymphocyte recognition
Authors: Haurum John S. , Tan Linda , Arsequell Gemma , Frodsham Penny , Lellouch Annemarie C. , Moss Paul A. H. , Dwek Raymond A. , McMichael Andrew J. , Elliott Tim 
Published: March 2007

AbstractThis study extends our previous observation that glycopeptides bind to class I major histocompatibility complex (MHC) molecules and elicit carbohydrate‐specific CTL responses. The Sendai virus nucleoprotein wild‐type (WT) peptide (FAPGNYPAL) binds H‐2Db using the P5‐Asn as an anchor. The peptide K2 carrying a P5 serine substitution did not bind Db. Surprisingly, glycosylation of the serine (K2‐O‐GlcNAc) with N‐acetylglucosamine (GlcNAc), a novel cytosolic O‐linked glycosylation, partially restored peptide binding to Db. We argue that the N‐acetyl group of GlcNAc may fulfil the hydrogen bonding requirements of the Db pocket which normally accomodates P5‐Asn. Glycosylation of the P5‐Asn residue itself abrogated binding similar to K2, probably for steric reasons. The peptide K2‐O‐GlcNAc readily elicited Db‐restricted cytotoxic T lymphocytes (CTL), which did not cross‐react with K2 or WT. However, all Db‐restricted CTL raised against K2‐O‐GlcNAc cross‐reacted strongly with another glycopeptide, K3‐O‐GlcNAc, where the GlcNAc substitution is on a neighboring P4‐Ser. Furthermore, Db‐restricted CTL clones raised against K2‐O‐GlcNAc or K3‐O‐GlcNAc displayed a striking TCR conservation. Our interpretation is that the carbohydrate of K2‐O‐GlcNAc not only mediates binding to Db, but also interacts with the TCR in such a way as to mimic K3‐O‐GlcNAc. This unusual example of molecular mimicry extends the known effects of peptide glycosylation from what we and others have previously reported: glycosylation may create a T cell neo‐epitope, or, conversely, abrogate recognition. Alternatively, glycosylation may block peptide binding to MHC class I and finally, as reported here, restore binding, presumably through direct interaction of the carbohydrate with the MHC molecule.
Interleukin‐4‐producing CD4+ NK1.1+ TCRα/βintermediate liver lymphocytes are down‐regulated by Listeria monocytogenes
Authors: Emoto Masashi , Emoto Yoshiko , Kaufmann Stefan H. E. 
Published: March 2007

AbstractExperimental infection of mice with the intracellular bacterium, Listeria monocytogenes, provides a paragon model for immune defence dominated by T helper type 1 (Th1) responses. Potent production of interleukin (IL)‐12 by infected macrophages is considered the determining factor in Th1 cell development. In contrast, it is assumed that IL‐4 producers remain virtually unstimulated in listeriosis. In the liver, the major target organ of listeriosis, an unusual T lymphocyte population exists with the intriguing phenotype CD4+NK1.1+ TCRα/βintermediate (TCRα/βint). Here we show that IL‐4‐producing CD4+NK1.1+TCRα/βint liver lymphocytes are down‐regulated early in listeriosis. We assume that curtailment of IL‐4‐producing CD4+NK1.1+TCRα/βint liver lymphocytes promotes unconstrained development of Th1 cells which are central to protection against intracellular bacteria.
Malignant B lymphocytes from non‐Hodgkin's lymphoma induce allogeneic proliferative and cytotoxic T cell responses in primary mixed lymphocyte cultures: An important role of co‐stimulatory molecules CD80 (B7‐1) and CD86 (B7‐2) in stimulation by tumor cells
Authors: Plumas Joël , Chaperot Laurence , Jacob Marie‐Christine , Molens Jean‐Paul , Giroux Claudine , Sotto Jean‐Jacques , Bensa Jean‐Claude 
Published: March 2007

AbstractWe analyzed the stimulating capacities of malignant B cells from non‐Hodgkin's lymphomas (NHL) to induce an allogeneic response in primary mixed lymphocyte reaction (MLR). T cells purified from a single healthy donor (KS) were used to compare the responses induced by either malignant or hyperplastic cells. Malignant B cells induced strong proliferation of KS cells independently of their level of expression of adhesion molecules. The KS cells after MLR were predominantly CD3+, CD25+, HLA‐DR+, Ki67+ and CD45RO+ T cells, and the CD4/CD8 ratio was heterogeneous (from 0.8 to 2.7). To investigate the role of co‐stimulatory molecules CD80 and CD86 for the stimulatory capacities of B cells, the expression of both molecules was analyzed before and during the MLR. Most fresh malignant B cells were negative for CD80 and CD86, whereas co‐cultured B cells expressed high levels of both molecules. This expression was crucial for T cell proliferation, since monoclonal antibodies directed against CD80 and CD86 completely abrogated the MLR. We also report that KS responding cells at the end of co‐culture were able to lyse fresh B cells used as stimulator cells to different extents (from 10 to 51%), and the level of lysis was enhanced after PMA activation of the target cells. Inhibition experiments using CD8 and CD4 mAb showed that effector cells were mainly CD8+. This report is the first to describe the accessory function of human malignant B cells from NHL and their sensitivity to lysis mediated by CD8+ T cells, and suggests new strategies for the development of antitumor immunity in NHL.