bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibronectin synthesis by activated T lymphocytes: up‐regulation of asurface‐associated isoform with signalling function
Authors: Wagner C. , Bürger A. , Radsak M. , Blum S. , Hug F. , Hänsch G. M. 
Published: March 2003

SummaryFibronectin (FN) is a major constituent of the extracellular matrix. We now provide evidence for a surface‐associated isoform of FN that is synthesized by T cells upon activation. The T‐cell‐derived FN has an unusual splice pattern: an additional domain, EDB, is produced whereas sequences within another domain, IIICS, are spliced out. CS1, the binding domain for very late antigen‐4 (VLA‐4), however, is still generated. To study the potential function of surface‐associated FN its synthesis was down‐regulated by an antisense oligonucleotide, then proliferation of T cells was induced by cross‐linked anti‐CD3. Proliferation was reduced as was expression of CD25. Moreover, when T cells were cultured in high density, the synthetic peptide QILDVPST, corresponding to CS1, inhibited proliferation, as did antibodies to VLA‐4. We propose that surface‐associated FN is a ligand for VLA‐4, which by binding to VLA‐4 on an adjacent cell, provides a costimulatory signal, thus sustaining T‐cell proliferation.
Thymus‐dependent modulation of Ly49 inhibitory receptor expression on NK1.1+γ/δ T cells
Authors: Hara T. , Nishimura H. , Hasegawa Y. , Yoshikai Y. 
Published: March 2003

SummaryMajor histocompatibility complex (MHC) class I‐specific inhibitory receptors are expressed not only on natural killer (NK) cells but also on some subsets of T cells. We here show Ly49 expression on γ/δ T cells in the thymus and liver of β2‐microglobulin‐deficient (β2m−/−) and C57BL/6 (β2m+/+) mice. Ly49C/I or Ly49A receptor was expressed on NK1.1+γ/δ T cells but not on NK1.1−γ/δ T cells. The numbers of NK1.1+γ/δ T cells were significantly smaller in β2m+/+ mice than in β2m−/− mice with the same H‐2b genetic background. Among NK1.1+γ/δ T cells, the proportions of Ly49C/I+ cells but not of Ly49A+ cells, were decreased in β2m+/+ mice, suggesting that cognate interaction between Ly49C/I and H‐2Kb is involved in the reduction of the number of Ly49C/I+γ/δ T cells in β2m+/+ mice. The frequency of Ly49C/I+ cells in NK1.1+γ/δ T cells was lower in both lethally irradiated β2m+/+ mice transplanted with bone marrow (BM) from β2m−/− mice and lethally irradiated β2m−/− mice transplanted with BM from β2m+/+ mice than those in adult thymectomized BM‐transplanted chimera mice. These results suggest that reduction of Ly49C/I+ NK1.1+γ/δ T cells in β2m+/+ mice is at least partly due to the down‐modulation by MHC class I molecules on BM‐derived haematopoietic cells or radioresistant cells in the thymus.
Protection of turkeys against Chlamydophila psittaci challenge by parenteral and mucosal inoculations and the effect of turkey interferon‐γ on genetic immunization
Authors: Vanrompay Daisy , Cox Eric , Kaiser Pete , Lawson Shelly , Van Loock Marnix , Volckaert Guido , Goddeeris Bruno 
Published: March 2003

SummaryPlasmid DNA (pcDNA1::MOMP A) expressing the major outer membrane protein of an avian Chlamydophila psittaci serovar A strain was tested for its ability to induce protective immunity against challenge with the same C. psittaci serovar. A combined parenteral (intramuscular injection) and mucosal route (DNA drops administered to the nares) of DNA inoculation was compared to three other, different routes of administration (intramuscular inoculation, DNA drops administered to the nares and aerosol immunization). In addition, the effect of turkey interferon gamma (tIFN‐γ) on intramuscular immunization was evaluated by co‐expressing pCIneo::tIFN‐γ. A significant level of protection was observed in turkeys immunized via the combined parenteral/mucosal route, the intramuscular route or by aerosol. Severe clinical signs and lesions were observed in the non‐vaccinated control groups, in 80% of turkeys inoculated with a mixture of pcDNA1::MOMP A and pCIneo::tIFN‐γ, and in 60% of turkeys vaccinated with DNA drops administered to the nares. The use of MOMP‐based DNA vaccination as a means of preventing severe clinical signs and lesions in a turkey model of C. psittaci infection was demonstrated, as was down‐regulation of the immune response by co‐expression of tIFN‐γ.
Interleukin‐12 primes CD4+ T cells for interferon‐γ production and protective immunity during Mycobacterium avium infection
Authors: Silva Regina A. , Flórido Manuela , Appelberg Rui 
Published: March 2003

SummaryInterleukin‐12 (IL‐12) is a crucial cytokine for the generation of a protective immune response against Mycobacterium avium infection. In contrast to infected control mice, IL‐12‐deficient mice were unable to control bacterial proliferation and their spleen T cells were almost unresponsive in vitro to specific antigens of M. avium. Susceptibility of mice deficient in IL‐12 was similar to that of interferon‐γ (IFN‐γ)‐deficient mice. These data indicate a crucial role of IL‐12 in the development of a T‐cell population able to produce IFN‐γ and to mediate protection against M. avium infection. Treatment of M. avium‐infected mice with IL‐12 induced CD4+ T cells with enhanced capacity to produce IFN‐γ as well as to confer increased protection against M. avium.
Characterization of equine E‐selectin
Authors: Hedges Jodi F. , Demaula Christopher D. , Moore Brian D. , Mclaughlin Bridget E. , Simon Scott I. , Maclachlan N. James 
Published: March 2003

SummaryExpression of E‐selectin on activated endothelium is a critical initial step that leads to extravasation of leucocytes during inflammation, yet E‐selectin is largely uncharacterized in several animal species including the horse. We have sequenced and compared E‐selectin genes derived from activated cultures of purified equine (horse), cervid (black‐tailed deer) and ovine (sheep) pulmonary artery endothelial cells (ECs). Phylogenetic and amino acid sequence comparisons indicate that bovine, cervid and ovine E‐selectin are similar, whereas human and equine E‐selectin are more closely related to each other than to the ruminant molecules. Human E‐ and P‐selectin‐specific monoclonal antibodies that also recognize equine E‐selectin were identified and used to characterize its expression. Expression of E‐selectin was more readily induced by lipopolysaccharide treatment in equine ECs than in human ECs and supported adhesion and activation of neutrophils, consistent with the extreme sensitivity of horses to endotoxaemia and septic shock.
Suppressive effect of locally produced interleukin‐10 on respiratory syncytial virus infection
Authors: Ruan Yan , Okamoto Yoshitaka , Matsuzaki Zensei , Endo Shuichiro , Matsuoka Tomokazu , Kohno Tadashi , Chazono Hideaki , Eiko Ito , Tsubota Kazuo , Saito Ichiro 
Published: March 2003

SummaryInterleukin (IL)‐10 is known to be a multifunctional cytokine. This study was designed to evaluate the role of IL‐10 during respiratory syncytial virus (RSV) infection using a C57BL/6 transgenic (TG) mouse model in which the expression of murine IL‐10 cDNA was regulated by a human salivary amylase promoter (IL‐10 TG mice). These mice expressed a large amount of IL‐10 in the nasal mucosa and in salivary glands. Viral replication in the respiratory tract after intranasal infection with RSV was suppressed significantly in IL‐10 TG mice compared to non‐transgenic controls. This suppression was IL‐10 specific, because it was prevented by treating mice with neutralizing anti‐IL‐10 antibodies. We also found that IL‐10‐stimulated T cells displayed cytotoxic activity against infected murine nasal epithelial cells. Previous data indicated that IL‐10 induces Fas ligand (L) expression on mouse T cells. Taken together, these data suggest that Fas/Fas L mediated cytotoxicity is involved in the suppression of RSV replication observed in IL‐10 TG mice after intranasal infection.
Beneficial effect of co‐polymer 1 on cytokine production by CD4 T cells in multiple sclerosis
Authors: Fellay BenoîT , Chofflon Michel , Juillard Catherine , Paunier Anne‐Marie , Landis Theodor , Roth Serge , Gougeon Marie‐Lise 
Published: March 2003

SummaryMultiple sclerosis (MS) has been associated with an imbalance in the T helper type 1 (Th1) and Th2 subsets. We investigated, at the single‐cell level, the synthesis of pro‐inflammatory cytokines by CD4 and CD8 T cells from MS patients. We report the relationship between priming of CD4 and CD8 T cells for interleukin‐2 (IL‐2), interferon‐γ (IFN‐γ) and tumour necrosis factor‐α (TNF‐α) and disease evolution in MS patients, clinically subdivided into relapsing–remitting MS (RRMS) in remission, RRMS in relapse, or chronic progressive MS (CPMS). Moreover, we report the in vivo influence of co‐polymer 1 (COP) treatment on the pattern of cytokine producers in RRMS patients. We show that the frequency of CD4 T cells primed for TNF‐α synthesis increased in all stages of MS, including RRMS remitting, and was normalized to control values in COP‐treated patients (43·2 ± 11·8% in treated patients versus 47 ± 7·3% in RRMS remitting versus 40·3 ± 8% in controls). In addition, a significant decrease in the frequency of CD4 T cells primed for IL‐2 was found in COP‐treated patients as compared to the other groups of patients, reaching values below that of controls (59·1 ± 9·9% in treated patients versus 70 ± 11·6% in RRMS remitting versus 67·1 ± 7·4% in controls). Unexpectedly, COP‐treated patients also showed a significantly decreased priming for IFN‐γ at the CD4 T‐cell level (9·1 ± 3·4% in treated patients versus 18·8 ± 0·6.4% in RRMS remitting versus 15·4 ± 4·7% in controls), but not at the CD8 T‐cell level. This bystander suppression on the inflammatory cells should be considered in the monitoring of MS patients submitted to COP treatment, in order to evaluate better its clinical efficacy.
Reduced T‐cell receptor CD3ζ‐chain protein and sustained CD3ε expression at the site of mycobacterial infection
Authors: Seitzer Ulrike , Kayser Klaus , Höhn Hanni , Entzian Peter , Wacker Hans‐Heinrich , Ploetz Sabine , Flad Hans‐Dieter , Gerdes Johannes , Maeurer Markus J. 
Published: March 2003

SummaryControl of mycobacterial infection by the cellular immune system relies both on antigen‐presenting cells and on T lymphocytes. The quality of an effective cellular immune response is dependent on functional signal transduction residing in the cytoplasmic tails of the T‐cell receptor CD3 components. In order to investigate potential effects of mycobacteria on T‐cell receptor signalling, we examined the protein expression of T‐cell signal transduction molecules (CD3ζ, ZAP‐70, p59fyn, p56l ck). In Western blots of peripheral blood mononuclear cells of Mycobacterium tuberculosis infected patients, only the CD3ζ‐chain showed a marked reduction in protein expression. To investigate the situation in situ, immunoenzymatic and immunofluorescence stainings for CD3ε and CD3ζ expression were performed on sections of normal lymphoid tissue, M. leprae infected and sarcoid tissue. CD3ε and CD3ζ expression were similar with respect to intensity, localization and the number of cells stained in normal lymphoid tissue and in sarcoid granulomas. In contrast, the granulomas of M. leprae infected tissues showed a significantly reduced expression of CD3ζ compared to CD3ε. Using double immunofluorescence analysis, virtually no CD3ζ expression could be detected in comparison to the CD3ε expression in the lesions. Apparently, mycobacteria are capable of significantly reducing CD3ζ‐chain expression, which may be restored by cytokines. IL‐2‐enhanced ζ‐chain expression and T‐cell effector functions, defined by interferon‐γ release, in M. tuberculosis‐specific and human leucocyte antigen‐DR restricted CD4+ T cells isolated from granuloma lesions from patients with pulmonary tuberculosis. Because CD3ζ is essential for CD3 signalling and for eliciting T‐cell effector functions, reduced CD3ζ protein expression could result in altered signal transduction and inefficient T‐cell effector functions. Alternatively, reduced CD3ζ‐chain expression may protect T cells from repetitive TCR stimulation associated with anergy or apoptosis.
Synergistic interactions of the two classes of ligand, sialyl‐Lewisa/x fuco‐oligosaccharides and short sulpho‐motifs, with the P‐ and L‐selectins: implications for therapeutic inhibitor designs
Authors: Galustian Christine , Childs Robert A. , Stoll Mark , Ishida Hideharu , Kiso Makoto , Feizi Ten 
Published: March 2003

SummaryThe E‐, L‐ and P‐selectins are carbohydrate‐recognizing cell‐adhesion molecules mediating selective leucocyte recruitment in inflammation. The 3′‐sialyl‐ and 3′‐sulpho‐oligosaccharides of Lewisx (Lex) and Lewisa (Lea) series are bound by them, but for high‐avidity binding of P‐ and L‐selectins to the glycoprotein counter‐receptor known as P‐selectin glycoprotein ligand, PSGL‐1, there is a requirement for sulpho‐tyrosines neighbouring a sialyl‐Lex glycan. The two selectins can also bind 3‐O‐ or 6‐O‐sulphated galacto‐lipids (sulphatides). Here we compare some features of the interactions of P‐ and L‐selectins with a novel lipid‐linked sulpho‐tyrosine probe, and with the sulphatides and neoglycolipids of sialyl‐ and sulpho‐Lex/Lea fuco‐oligosaccharides. The sulpho‐tyrosine probe is bound by both selectins. There are close similarities in the interactions of the two selectins with sulpho‐tyrosine and the sulphatides; the binding is relatively resistant to chelation of calcium ions, in contrast to the absolute requirement of calcium ions with the long fuco‐oligosaccharides, including 6‐sulpho‐sialyl‐Lex. With both selectins, there is striking synergy in binding signals elicited by the two ligand types when presented as equimolar mixtures on a matrix. Thus, there are two operationally distinct binding sites on both L‐ and P‐selectin; and the binding sites for sulphate groups in the two ligand types are probably distinct. When sulpho‐tyrosine and sialyl‐Lex are presented on liposomes, a potent inhibitory activity is generated toward the binding of P‐selectin to HL60 cells, with 50% inhibitory concentration (IC50) values in the nanomolar range. These features of the lipid‐linked ligand analogues, and the simple approach for their display on liposomes, may have applications in designs and screening of selectin inhibitors as anti‐inflammatory compounds.
Endothelial cell and cAMP regulation of T‐cell CD40 ligand: relevance of calcium/calmodulin‐dependent kinase IV signalling
Authors: Nielson Christopher P. , Wingett Denise 
Published: March 2003

SummaryCD40 ligand (CD40L) expression is now recognized to contribute in the pathogenesis of vascular disease. Because increased CD40L has been associated with myocardial infarction, effects of endothelial cells and cAMP with respect to CD40L regulation may be of clinical relevance. In the present study, endothelial cells are shown to markedly increase CD40L on naïve CD4+ T cells with a more modest effect on memory T cells. Furthermore, the addition of dibutyryl cyclic AMP (dbcAMP) synergistically increased naïve cell CD40L but inhibited memory cell CD40L. Although it has previously been recognized that human endothelial cells can increase T‐cell CD40L, this is the first description of the difference in responses of naïve and memory cells and the first demonstration of synergistic effects of endothelial cells and cAMP on CD40L regulation. Consistent with previous reports that CD40L regulation is distinctive, another marker of early activation (CD69) was not similarly regulated. The mechanisms of CD40L regulation were related to calcineurin and calcium/calmodulin dependent kinase IV (CaMKIV) signalling pathways. Endothelial cell costimulation of CD40L was found to be dependent upon calcineurin activity while cAMP actions to increase CD40L were dependent upon CaMKIV. Expression of a dominant negative CaMKIV construct further indicated an important role for CaMKIV in regulation of CD40L and cAMP responses. These data indicate that endothelial cell costimulation can interact with cAMP through calcium signalling pathways to synergistically enhance CD40L expression. Because increased CD40L is associated with atherosclerotic plaque and instability, results are relevant to the pathogenesis of atherosclerosis and myocardial infarction.
Products from human mast cell line cells enhance the production of interferon‐γ by CD8+ and CD4+ T cells
Authors: De Pater‐Huijsen Francina L. , De Riemer MariËlle J. , Reijneke Richard M. R. , Pompen Marjolein , Lutter René , Jansen Henk M. , Out Theo A. 
Published: March 2003

SummaryIn patients with allergic asthma, T‐cell cytokines are implicated in the regulation of the local inflammation in the airways. The ability of sensitized mast cells to release mediators and cytokines early upon allergen stimulation makes them important candidates for local immunoregulation. We have studied the effects of human mast cells on T cells with the use of the human mast cell line HMC‐1. We showed that activated human mast cells or their soluble products induced and enhanced the interferon‐γ (IFN‐γ) production by T cells up to about 60‐fold. The production of interleukin (IL)‐4 was hardly affected and that of IL‐5 was slightly enhanced. The enhancement of IFN‐γ production was induced both in polyclonal CD4+ and CD8+ T cells and in CD4+ and CD8+ T‐cell clones. Further characterization of the factors involved demonstrated a molecular mass above 30 000. Our results implicate that by this mechanism mast cells may account for a negative feedback system locally down‐regulating allergen‐induced T helper 2 responses via IFN‐γ production by the T cells.
Identification of cytotoxic T lymphocyte epitopes of human herpesvirus 8
Authors: Micheletti Fabiola , Monini Paolo , Fortini Cinzia , Rimessi Paola , Bazzaro Martina , Andreoni Massimo , Giuliani Massimo , Traniello Serena , Ensoli Barbara , Gavioli Riccardo 
Published: March 2003

SummaryThe human herpesvirus 8 (HHV‐8) is a human γ2‐herpesvirus that is implicated in the development of Kaposi's sarcoma (KS), primary effusion lymphoma and Castelman's disease. Since the responses of cytotoxic T lymphocytes (CTL) play a key role in the control of herpesvirus infection, it is important to identify and to characterize the CTL target epitopes of HHV‐8 viral antigens. In this study, using peptide‐binding motifs, we selected potential human leucocyte antigen (HLA)‐A2‐binding peptides from kaposin A and glycoprotein H (gH), that are latent and lytic HHV‐8 antigens, respectively. HLA‐A2‐binding peptides were tested for their capacity to induce CTL responses in HHV‐8‐negative healthy donors. By this approach, we found that the majority of individuals responded to two HHV‐8‐derived CTL epitopes, namely, VLLNGWRWRL (amino acids 16–25), which derives from kaposin A, and FLNWQNLLNV (amino acids 59–68), which derives from gH. In addition, memory CTL responses to these epitopes were detected in disease‐free individuals infected by HHV‐8 demonstrating that the two epitopes are relevant targets of CTL‐mediated immunity in vivo. The identified epitopes may be investigated for the development of immunotherapeutic strategies against HHV‐8‐associated malignancies.
Opposing cytokine‐specific effects of all trans‐retinoic acid on the activation and expression of signal transducer and activator of transcription (STAT)‐1 in THP‐1 cells
Authors: Chen Qiuyan , Ma Yifan , Ross A. Catharine 
Published: March 2003

SummaryThe regulation of signal transducer and activator of transcription‐1 (STAT‐1) by cytokines and all‐trans‐retinoic acid (RA) was investigated in THP‐1 monocytic cells cultured with RA and stimulated with lipopolysaccharide (LPS), tumour necrosis factor‐α (TNF‐α), interferon‐β (IFN‐β), and IFN‐γ, individually or in combinations. While RA (10−8 m) alone did not alter STAT‐1 activation or expression in THP‐1 cells, RA enhanced or prolonged STAT‐1 activation (tyrosine 701 phosphorylation) and gene expression (mRNA and protein) induced by either IFN‐β or IFN‐γ. However, in contrast, RA reduced STAT‐1 activation and gene expression induced by LPS and/or TNF‐α by about 50–70%, and lowered in vitro DNA binding activity to both a STAT‐1 consensus element and a nuclear factor kappa B (NFκB) binding element. These results imply that RA can significantly rebalance STAT‐1‐dependent responses, and that one of the mechanisms may be through the inhibition of the NFκB pathway.
Cross‐presentation of cell‐associated antigens by CD8α+ dendritic cells is attributable to their ability to internalize dead cells
Authors: Schulz Oliver , Reis e Sousa Caetano 
Published: March 2003

SummaryIn the mouse, cross‐presentation is an exclusive property of the CD8α+ subset of dendritic cells (DC) but the basis for this selectivity remains unclear. Here we report that splenic CD8α+ DC are much superior to other DC subsets in internalizing dying cells in vitro. In contrast, CD8α+, CD8α– CD4+ and CD8α– CD4– DC subsets phagocytose bacteria or latex beads to a similar extent. Although CD8α+ DC are better than CD4+ DC at presenting ovalbumin (OVA)‐loaded splenocytes to naïve OT‐I T lymphocytes, CD4+ DC are better at presenting OVA‐expressing Escherichia coli to the same T cells. In both cases, presentation is abrogated by lactacystin. These results show that both splenic CD8α+ and CD8α– DC can present exogenous antigens on major histocompatibility complex (MHC) class I via a proteasome‐dependent pathway and suggest that the specialized cross‐presenting function of CD8α+ DC is a result of their ability to endocytose dying cells rather than a unique pathway for handling endosomal contents.
Haptoglobin directly affects T cells and suppresses T helper cell type 2 cytokine release
Authors: Arredouani M. , Matthijs P. , Van Hoeyveld E. , Kasran A. , Baumann H. , Ceuppens J. L. , Stevens E. 
Published: March 2003

SummaryT helper cell type 1 (Th1) and type 2 (Th2) immune responses are characterized by a different pattern of cytokine expression following T‐cell activation. Alterations of the ratio of Th1 to Th2 cells are important determinants of susceptibility to viral and parasitic infections, allergies, anti‐tumour responses, and autoimmunity. In this work we bring new evidence for an effect of haptoglobin (Hp), a positive acute‐phase protein, on T‐lymphocyte functions. We show that Hp specifically interacts with both resting and activated CD4+ and CD8+ T cells. This specific binding results in a strong suppression of induced T‐cell proliferation. In addition, Hp exhibits a strong in vitro inhibitory effect on Th2 cytokine release, while the production of interferon‐γ (IFN‐γ) and interleukin‐2 (IL‐2) is only slightly inhibited at high Hp doses. As a result, the presence of Hp promotes Th1 activation over Th2 activation in vivo as evidenced in Hp‐deficient mice. Anti‐CD3 monoclonal antibody injection indeed resulted in predominant IL‐4 production in Hp−/− mice, in contrast to predominant IFN‐γ production in Hp+/+ mice. We conclude that Hp plays a modulating role on the Th1/Th2 balance by promoting a dominant Th1 cellular response. This points to a role of acute‐phase proteins in balancing immune responses.
Group support systems in Hong Kong: an action research project
Authors: Davison Robert , Vogel Doug 
Published: March 2003

Abstract.The last dozen years have seen a considerable investment of resources into the research and development of group support systems (GSS) technology. This paper describes how GSS was used to support a process improvement project in a Hong Kong accounting firm. Although the project encountered many difficulties, the application of action research facilitated the adaptation of the GSS to the shifting circumstances, and the project was successfully completed. A variety of lessons concerning the use of GSS are presented, while increased use of action research in complex organizational contexts is recommended.