bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-incubation of pig islet cells with spleen cells from non-obese diabetic mice causes decreased insulin release by non-T-cell- and T-cell-mediated mechanisms
Authors: You S , Rivereau A-S , Gouin E , Saï P 
Published: March 2003

Summary
In vitro studies were conducted in the non-obese diabetic (NOD) mouse, prone to Type 1 autoimmune diabetes, to investigate the mechanisms involved in cell-mediated rejection of pig islet xenografts. Our previous work concerning the mechanisms of proliferation of xenogeneic lymphocytes to pig islet cells (PIC) was not indicative of PIC impairment. Consequently, a test was developed based on perifusion analysis of the alteration of basal and stimulated insulin release from adult PIC incubated with mouse splenocytes or subsets. Compared with PIC incubation alone or with syngeneic pig splenocytes, co-incubation with mouse whole spleen cells resulted in a decrease of basal and stimulated insulin release (P &lt; 0·001). Two components of this alteration were detected separately: PIC impairment was decreased (P &lt; 0·01) after removal of plastic-adherent cells from spleen cells, but maintained (P &lt; 0·01) when plastic-adherent cells alone were co-incubated with PIC. The increase of murine interleukin-1β when mouse plastic-adherent spleen cells were cultured with PIC (P &lt; 0·04) was indicative of macrophage activation. Soluble factors produced during co-incubation of mouse splenocytes or plastic-adherent cells with PIC were involved in the impairment process, since supernatant fluids collected during previous PIC–mouse cell co-incubations directly altered (P &lt; 0·01) insulin release from PIC. Moreover, impairment of PIC by mouse spleen cells was abolished (P &lt; 0·01) by gadolinium chloride (which inhibits macrophages), but not by cyclosporin A. Another mechanism was apparent, since co-incubation of PIC with purified mouse T cells or CD4+ T cells, re-mixed with antigen-presenting cells, led to a decrease (P &lt; 0·01) of insulin release. This model, based on the alteration of dynamic basal and stimulated insulin release, is indicative of in vitro cell-mediated alteration of PIC in the NOD mouse. The effect of whole spleen cells was rapid, and a crucial role was played by plastic-adherent cells. Two mechanisms were responsible for the behaviour of these cells: an early direct effect (at least in part via soluble products); and the indirect presentation of PIC xenoantigens (leading to impairment by CD4+ T lymphocytes).
Antigen-specific suppression of cultured lymphocytes from patients with neurocysticercosis
Authors: Bueno E C , Vaz A J , Machado L R , Livramento J A , Ávila S L M , Ferreira A W 
Published: March 2003

SummaryThe biological parasite–host interactions involved in neurocysticercosis (NC) are of a complex nature. A lymphoproliferation assay was performed using mononuclear cells from 11 patients with NC, who were classified according to the alterations obtained by imaging examinations. Antigen extracts from the membrane and/or scolex of Taenia solium and from the vesicular fluid of Taenia crassiceps were used. Mononuclear cells from patients with NC showed antigen-specific suppression when compared with a control group. The patients presenting calcified cysts showed higher suppression when compared with patients in the active phase of disease. The antigen in the vesicular fluid of T. crassiceps seems to play a suppressor role in vitro, completely inhibiting cell proliferation induced by the mitogens phytohaemagglutinin, concanavalin A and pokeweed mitogen.
De-novo humoral immune responses to cancer-associated autoantigens during transition from chronic liver disease to hepatocellular carcinoma
Authors: Zhang J Y , Zhu W , Imai H , Kiyosawa K , Chan E K L , Tan E M 
Published: March 2003

Summary
A feature of hepatocellular carcinoma (HCC) is that antecedent liver cirrhosis and chronic hepatitis are common precursor conditions and during transition to malignancy some patients develop autoantibodies which were not present during the preceding chronic liver disease phase. Serum samples from such patients can be used to immunoscreen cDNA expression libraries to identify genes encoding the new autoantigens. We demonstrate here the de novo appearance of antibodies to p62, a cytoplasmic protein which has been shown to bind to a developmentally regulated fetal species of insulin-like growth factor II (IGF-II) mRNA. Another antibody appearing during the transition period was against CENP-F, a cell cycle-related nuclear protein with maximum expression in the G2 and M phases of the cell cycle and previously shown to have a high association with malignancy. In three additional patients in whom serial serum samples were examined, new appearance of anti-p62 was detected in two patients and anti-CENP-F in one patient. This study demonstrates that transition to malignancy can be associated with autoantibody responses to certain cellular proteins which might have some role in tumorigenesis.
Flow cytometric measurement of intracellular migration inhibition factor and tumour necrosis factor alpha in the mucosa of patients with coeliac disease
Authors: O'Keeffe J , Lynch S , Whelan A , Jackson J , Kennedy N P , Weir D G , Feighery C 
Published: March 2003

SummaryThere is increasing evidence that proinflammatory cytokines contribute to many of the small intestinal features in coeliac disease. The aim of the study was to investigate the expression of two proinflammatory cytokines, migration inhibition factor (MIF) and tumour necrosis factor alpha (TNF-α) in duodenal biopsy specimens from patients with coeliac disease on a gluten-free diet and normal control subjects. A flow cytometric system was used to analyse intracellular protein levels of MIF and TNF-α in freshly isolated cells from duodenal biopsies taken from 12 patients with treated coeliac disease and 10 healthy control subjects. From the biopsy specimens, single cell suspensions of the epithelium and lamina propria were prepared using EDTA/DTT and enzymes. Intracellular cytokine expression was studied in intraepithelial lymphocytes (IELs), lamina propria T cells (LP T) and intestinal epithelial cells using different surface labelling antibodies. MIF protein was constitutively expressed in IELs, LP T cells and epithelial cells from normal intestinal mucosa. In contrast, although TNF-α was found in LP T cells, this cytokine was virtually undetectable in either IELs or epithelial cells. In coeliac disease, intracellular levels of MIF were significantly higher in epithelial cells compared with control subjects (P = 0·005). Raised levels of TNF-α were found in epithelial cells (P = 0·03) as well as IELs (P = 0·045) from coeliac patients compared with controls. The findings from this study show up-regulated expression of MIF and TNF-α in IELs and epithelial cells of histologically normal mucosa in patients with coeliac disease. Increased expression of proinflammatory cytokines in cells occupying the epithelial layer could help explain the rapidity with which the coeliac mucosa may respond to gluten challenge.
Localization of pro-inflammatory (IL-12, IL-15) and anti-inflammatory (IL-11, IL-13) cytokines at the foetomaternal interface during murine pregnancy
Authors: Zourbas S , Dubanchet S , Martal J , Chaouat G 
Published: March 2003

SummaryThe involvement of some interleukins (ILs) in early and established pregnancy has been convincingly demonstrated, but little is known about the potential role of the more recently discovered ones. However, since many of these have positive or negative regulatory effects on both NK and T cells, it is highly probable that they also have regulatory functions in both implantation and placental development. Therefore, as a first step in tackling this problem, we have investigated whether several recently described pro- (IL-12, IL-15) and anti-inflammatory (IL-11, IL-13) cytokines were expressed at the uteroplacental interface by use of immunohistochemistry at different stages of gestation in mice.Each of these molecules was found at the foetomaternal interface, with specific distributions and patterns of expression depending on both the cytokine itself and the stage of pregnancy. The significance of these data is discussed.
Elevated serum levels of matrix metalloproteinase-9 (MMP-9) in Kawasaki disease
Authors: Takeshita S , Tokutomi T , Kawase H , Nakatani K , Tsujimoto H , Kawamura Y , Sekine I 
Published: March 2003

SummaryMatrix metalloproteinases (MMPs) play an important role in the progression of tumour cells and the invasion of inflammatory cells by degrading the extracellular matrix. In the MMP family, MMP-9 gelatinase is thought to contribute to the pathogenesis of inflammatory arteritis by disrupting the elastic lamina. The aim of the present study is to investigate the potential role of MMP-9 in Kawasaki disease (KD), an acute type of systemic vasculitis in children. We studied the total levels of MMP-9 (free proMMP-9 and free MMP-9) in the sera using a new assay system and the expression of MMP-9 mRNA in the leucocytes using reverse transcription-polymerase chain reaction in 18 patients with KD, 10 patients with sepsis and 10 healthy children (HC). The serum MMP-9 levels were significantly higher (P &lt; 0·01) in the acute phase of KD than in the acute phase of sepsis and HC. In the time course of KD, the serum MMP-9 levels decreased significantly (P &lt; 0·01) from the subacute through the convalescent phases. In the acute phase of KD, the serum MMP-9 levels showed a significantly positive correlation (P &lt; 0·05) with the circulating leucocyte counts, especially the neutrophil counts. Furthermore, the expression of MMP-9 mRNA in the circulating leucocytes increased in the acute phase of KD and decreased from the subacute through the convalescent phases. These findings indicate that an excessive amount of MMP-9 is present in the plasma during the acute phase of KD, thus suggesting that circulating leucocytes may be a source of the MMP-9 secreted into the circulation.
T-cell re-population in HIV-infected children on highly active anti-retroviral therapy (HAART)
Authors: King D J S , Gotch F M , Larsson-Sciard E-L 
Published: March 2003

Summary
In this pilot study, we address the nature of the re-population of the T-cell compartment in HIV-1+ (Human Immunodeficiency Virus 1), vertically infected children placed on successful regimens of HAART (highly active anti-retroviral therapy) incorporating 2 NRTI and a protease inhibitor. The clonality of the T-cell compartment and the abundance of RTEs (Recent Thymic Emigrants) were determined 2 weeks before and 20 weeks after initiation of HAART in a subgroup of children taking part in the PENTA (Paediatric European Network for the Treatment of AIDS) 5 trial. Analysis of the clonality of the circulating T-cell compartment was assessed using CDR3 spectratyping and analysed using the Kolmogorov–Smirnov two sample test. This revealed that a high degree of T-cell clonal restriction still exists 5 months into therapy, despite the appearance of previously undetectable T-cell clones within the periphery. We detected no increase in RTE abundance in this 5 month period, as determined by PCR detection of TRECs (T-Cell Receptor Excision Circles). We conclude that the observed re-population of T cells within the periphery of treated children is heavily reliant upon the maintenance/expansion of pre-existing cells during the 5 month period immediately following the initiation of therapy.
Generationin vitroof B-cell chronic lymphocytic leukaemia-proliferative and specific HLA class-II-restricted cytotoxic T-cell responses using autologous dendritic cells pulsed with tumour cell lysate
Authors: Goddard R V , Prentice A G , Copplestone J A , Kaminski E R 
Published: March 2003

SummaryImmunotherapy using dendritic cells has shown encouraging results in both haematological and non-haematological malignancies. In this study, monocyte-derived dendritic cells from patients with B-CLL were cultured for 6 days in the presence of IL-4 and GM-CSF. Autologous B-CLL T-cells were cultured alone or with B-CLL lysate-pulsed and unpulsed autologous dendritic cells. IFN-γ secretion was assessed using ELISA. Cytotoxicity was assessed, after 21 days in culture and re-stimulation, using flow cytometry with and without blockade by anti-HLA class I, anti-HLA class II, anti-CD4, anti-CD8 and anti-TCRαβ monoclonal antibodies. B-CLL T cells stimulated with B-CLL lysate-pulsed autologous dendritic cells showed a significant (P = 0·0004) increase in IFN-γ secretion and a significant (P = 0·0008) increase in specific cytotoxicity to autologous B-cell targets, but none to autologous T cell or B cell targets from healthy individuals. B-CLL T cells cultured with (non-B-CLL) B-cell lysate-pulsed B-CLL dendritic cells showed no significant response. Pulsing dendritic cells from healthy volunteers with an autologous (non-B-CLL) B-cell lysate did not stimulate proliferation, cytokine production or cytotoxicity by autologous T cells. Pulsing B-CLL dendritic cells with allogeneic B-CLL lysates and culturing with autologous T-cells elicited cytotoxicity against autologous B-CLL targets in some cases, but not in others. Cytotoxicity was significantly reduced by blocking with anti-HLA class II (P = 0·001), anti-TCRαβ (P = 0·03) and anti-CD4 (P = 0·046) antibodies. Phenotyping of the responding T-cell population demonstrated the majority to be CD4 positive. Our data demonstrate that HLA class II-restricted proliferative and cytotoxic T-cell responses to B-CLL can be generated using autologous dendritic cells pulsed with tumour cell lysate.
Children with atopic dermatitis who carry toxin-positiveStaphylococcus aureusstrains have an expansion of blood CD5− B lymphocytes without an increase in disease severity
Authors: Arkwright P D , Cookson B D , Haeney M R , Sanyal D , Potter M R , David T J 
Published: March 2003

SummaryToxin-positive strains of Staphylococcus aureus (T + S. aureus) are present on the skin of some but not all patients with atopic dermatitis. Many staphylococcal toxins are superantigens, which can stimulate the immune response and thus may potentially lead to the very high levels of IgE characteristic of this condition, as well as exacerbating the clinical disease. The aim of this study was to determine whether the presence of T + S. aureus on the skin of children with atopic dermatitis was associated with in vivo evidence of a heightened humoral immune response, higher IgE levels and more severe clinical disease. Toxin gene expression in S. aureus isolated from the eczematous lesions of 28 children with atopic dermatitis was assessed by PCR. Clinical and immune data were also collected from this cohort. Thirteen of the 28 children (46%) were colonized with T + S. aureus strains. The presence of T + S. aureus was associated with a significant expansion in peripheral blood CD5− B cells (P = 0·01), and the more toxin types identified the greater the B-cell expansion (P = 0·002). However, in this cohort of children with atopic dermatitis, despite th in vivo expansion of B cells in children harbouring T + S. aureus, there was no associated increase in IgE levels or in clinical disease severity scores.
Intranasal BCG vaccination protects BALB/c mice against virulentMycobacterium bovisand accelerates production of IFN-γ in their lungs
Authors: Lyadova I V , Vordermeier H M , Eruslanov E B , Khaidukov S V , Apt A S , Hewinson R G 
Published: March 2003

SummaryLocal immune reactivity in the lungs of BALB/c mice was studied following (i) intranasal (i.n.) vaccination with Mycobacterium bovis BCG, (ii) intravenous (i.v.) challenge with a virulent M. bovis field isolate and (iii) i.n. vaccination with M. bovis BCG followed by i.v. challenge with an M. bovis field isolate. The results demonstrated that i.n. vaccination with BCG induced a high degree of protection against systemic M. bovis challenge, and that this protection correlated with a rapid production of IFN-γ after M. bovis challenge by lung T cells from vaccinated mice.
IL-15-induced conversion of monocytes to mature dendritic cells
Authors: Saikh K U , Khan A S , Kissner T , Ulrich R G 
Published: March 2003

SummaryIL-15 is produced by a wide variety of tissues in response to inflammatory stimuli. We examined the effect of IL-15 in supporting the maturation of monocytes to dendritic cells in ex vivo culture. IL-15 transformed CD14+ monocytes to mature dendritic cells. These dendritic cells were similar to those obtained from monocyte cultures treated with a combination of the cytokines GM-CSF, IL-4 and TNF-α. The effects of IL-15 did not depend on endogenously produced GM-CSF. The IL-15-induced dendritic cells also expressed chemokines and stimulated strong allo-responses that were characteristic of mature dendritic cells. These data indicate that CD14+ monocytes respond to IL-15 by undergoing morphological transformation and acquiring characteristic dendritic cell features that facilitate antigen-specific responses of T cells. Thus, the release of IL-15 by inflammatory stimuli may induce the conversion of monocytes to immuno-stimulatory dendritic cells to support primary immune responses against pathogens.
Cytokine receptor signalling in neonatal macrophages: defective STAT-1 phosphorylation in response to stimulation with IFN-γ
Authors: Maródi L , Goda K , Palicz A , Szabó G 
Published: March 2003

SummaryWe reported earlier that neonatal monocyte-derived macrophages (MDM) could not be fully activated with IFN-γ, a finding that could not be attributed to lower expression of IFN-γ receptors on the neonatal cells. In this study we explored elements of IFN-γR-mediated signalling in cord monocytes and MDM. Intracellular expression of STAT-1 was analysed by flow cytometry. We have assessed phosphorylation of STAT-1 by using MoAbs that distinguish native and phosphorylated forms of STAT-1 on a discrete cell basis. Using MoAbs against the native form of STAT-1 revealed comparable expression of this protein in cord and adult cells (both monocytes and MDM). However, STAT-1 phosphorylation in response to IFN-γ was significantly decreased in neonatal monocytes (P &lt; 0·05) and MDM (P &lt; 0·01) compared to adult cells (n &gt; 5 for each). These data suggest deficient cytokine-receptor signalling in neonatal mononuclear phagocytes exposed to IFN-γ. We propose that decreased STAT-1 phosphorylation and activation may represent developmental immaturity and may contribute to the unique susceptibility of neonates to infections by intracellular pathogens.
Comparative protective effects of recombinant DNA andMycobacterium bovisbacille Calmette–Guérin vaccines againstM. aviuminfection
Authors: Martin E , Triccas J A , Kamath A T , Winter N , Britton W J 
Published: March 2003

SummaryA range of strategies are being explored to develop more effective vaccines against mycobacterial infection, including immunization with DNA plasmids encoding single mycobacterial bacterial genes and the use of recombinant live vectors based on the current vaccine, Mycobacterium bovis bacille Calmette–Guérin (BCG). We have compared these two approaches using a model of virulent M. avium infection, and the gene for the immunodominant 35 kDa protein which is shared by M. avium and M. leprae, but absent from BCG. Recombinant BCG over-expressing the M. avium 35 kDa protein (BCG-35) induced strong antigen-specific proliferative and interferon-γ (IFN-γ)-secreting T cell responses. These were comparable to those induced by a single immunization with a plasmid expressing the same antigen (DNA-35); however, repeat DNA-35 immunization evoked the strongest IFN-γ release. Immunization with BCG-35 significantly reduced the growth of virulent M. avium, although this effect was similar to that induced by wild-type BCG. Immunization with DNA-35 resulted in significantly greater (2 × log10) reduction in the growth of M. avium. Prime-boost strategies combining DNA-35 and BCG-35 increased the protective effect above that achieved by BCG-35, but they were not more protective than DNA-35 alone. Therefore, recombinant BCG-35 and BCG induced similar levels of protection in this model, and maximal protection against M. avium infection was attained by immunization with DNA encoding the 35 kDa protein.
Death-inducing receptors and apoptotic changes in lymphocytes of patients with heart transplant vasculopathy
Authors: Ankersmit H J , Moser B , Roedler S , Teufel I , Zuckermann A , Roth G , Lietz K , Back C , Gerlitz S , Wolner E , Boltz-Nitulescu G 
Published: March 2003

SummaryThe specific role of lymphocyte apoptosis and transplant-associated atherosclerosis is not well understood. The aim of our study was to investigate the impact of T cell apoptotic pathways in patients with heart transplant vasculopathy. Amongst 40 patients with cardiac heart failure class IV who have undergone heart transplantation, 20 recipients with transplant-associated coronary artery disease (TACAD) and 20 with non-TACAD were investigated one year postoperative. Expression of CD95 and CD45RO, and annexin V binding were measured by FACS. Soluble CD95, sCD95 ligand (sCD95L), tumour necrosis factor receptor type 1 (sTNFR1), and histones were measured in the sera by ELISA. The percentage of cells expressing CD3 and CD4 was significantly reduced in TACAD as well as in non-TACAD patients as compared with control volunteers. Interestingly, the proportion of CD19+ (B cells) and CD56+ (NK) cells was increased in TACAD groups (versus non-TACAD; P &lt; 0·01, and P &lt; 0·001, respectively). In contrast to sCD95, the expression of CD95 (APO-1/Fas) and CD45RO (memory T cells), and sCD95L were significantly increased in non-TACAD and TACAD patients. T cell activation via CD95 with consecutive apoptosis was increased in both groups. The concentration of sTNFR1, IL-10 and histones was significantly elevated in sera from TACAD than non-TACAD patients, and in both groups than in healthy controls. These observations indicate that the allograft may induce a pronounced susceptibility of CD4+ T cells to undergo apoptosis and antibody-driven activation-induced cell death. This data may suggest a paradox immune response similar to that seen in patients with autoimmune diseases.
IL-15 in human visceral leishmaniasis caused byLeishmania infantum
Authors: MILANO S , BELLA G DI , D’AGOSTINO P , BARBERA C , CARUSO R , ROSA M LA , FERLAZZO V , VITALE G , RUSSA C LA , GAMBINO G , CHIFARI N , MANSUETO S , CILLARI E 
Published: March 2003

SummaryInterleukin (IL)-15 is a recently discovered cytokine with the ability to stimulate the proliferation activity of Th1 and/or Th2 lymphocytes. Here, we investigated the involvement of IL-15 in the immune response to Leishmania infantum infection by studying patients with visceral leishmaniasis (VL). We found that IL-15 is produced by leishmanial antigen (LAg)-stimulated peripheral blood mononuclear cells (PBMC) from active VL patients at a significantly higher level than those produced by cells from healed VL subjects or healthy controls. A significant increase in IL-15 serum blood levels was also observed in acute VL patients compared with healed ones. Furthermore, recombinant IL-15 had an appreciable effect in vitro in reducing IL-4 and increasing the production of IL-12 in response to LAg, but it was ineffective in altering the production of interferon-γ (IFN-γ). The production of endogenous IL-15 in acute VL patients appeared to be insufficient to activate both IFN-γ and IL-12, as attested by the absence of modification of these two cytokines by neutralization experiments in the presence of anti-IL-15 monoclonal antibodies (MoAB). On the contrary, the neutralization of IL-15 increased IL-4 production. Together, these results indicate that endogenous IL-15 plays a role in the suppression of Th2-type cytokines, even though it does not enhance the production of Th1 cytokines in acute VL patients. Since IL-15, in the presence of anti-IL-4 MoAb, caused a further increase in IL-12 production and led to a significant production of IFN-γ, one of its indirect effects on Th1 cell activation could be due to the latter’s effect on Th2 cytokines such as IL-4. Therefore, our observations indicate that there is a potential for IL-15 to augment the T-cell response to human intracellular pathogens.