bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monocyte-derived dendritic cell function in chronic hepatitis C is impaired at physiological numbers of dendritic cells
Authors: MacDonald A J , Semper A E , Libri N A , Rosenberg W M C 
Published: August 2010

SummaryMonocyte-derived dendritic cells (MoDCs) are a promising cellular adjuvant for effector immune responses against tumours and chronic viral infections, including hepatitis C virus (HCV). If autologous DC therapeutic approaches are to be applied in persistent HCV infections in patients, it is important to have an unambiguous understanding of the functional status of the cell type used, namely MoDCs from patients with chronic hepatitis C (CHC) infection. Because of conflicting published reports of either impaired or normal MoDC function in CHC infection, we re-examined the ability of MoDCs from CHC and normal healthy donors (NHD) to mature to an inflammatory stimulus [tumour necrosis factor (TNF)-α] and their subsequent functional capabilities. Expression of maturation-associated phenotypic markers [human leucocyte antigen (HLA)-DR, CD83, CD86, CD40], allostimulatory capacity in mixed lymphocyte reactions (MLRs) and CD40-ligand-induced cytokine and chemokine generation were compared in CHC- versus NHD-MoDCs. TNF-α-stimulated CHC-MoDCs up-regulated phenotypic markers, but to significantly lower levels than NHD-MoDCs. At physiological ratios of DCs to T cells, CHC-MoDCs were less allostimulatory than NHD-MoDCs, but not when DC numbers were substantially increased. CHC- and NHD-MoDCs generated equivalent amounts of cytokines [TNF-α, interleukin (IL)-1β, IL-6, IL-12p70, IL-15, IL-10] and chemokines [interferon-inducible protein (IP)-10, macrophage inflammatory protein (MIP)-1α, regulated upon activation, normal T expressed and secreted (RANTES)] after CD40 ligation. Because the functional defect was not apparent at high MoDC : T cell ratios, autologous MoDC therapy with sufficiently high numbers of DCs could, in theory, overcome any impairment of MoDC function in CHC.
Potato lectin activates basophils and mast cells of atopic subjects by its interaction with core chitobiose of cell-bound non-specific immunoglobulin E
Authors: Pramod S N , Venkatesh Y P , Mahesh P A 
Published: August 2010

SummaryA major factor in non-allergic food hypersensitivity could be the interaction of dietary lectins with mast cells and basophils. Because immunoglobulin E (IgE) contains 10–12% carbohydrates, lectins can activate and degranulate these cells by cross-linking the glycans of cell-bound IgE. The present objective focuses on the effect of potato lectin (Solanum tuberosum agglutinin; STA) for its ability to release histamine from basophils in vitro and mast cells in vivo from non-atopic and atopic subjects. In this study, subjects were selected randomly based on case history and skin prick test responses with food, pollen and house dust mite extracts. Skin prick test (SPT) was performed with STA at 100 µg/ml concentration. Histamine release was performed using leucocytes from non-atopic and atopic subjects and rat peritoneal exudate cells. SPT on 110 atopic subjects using STA showed 39 subjects positive (35%); however, none showed STA-specific IgE; among 20 non-atopic subjects, none were positive by SPT. Maximal histamine release was found to be 65% in atopic subjects (n = 7) compared to 28% in non-atopic subjects (n = 5); the release was inhibited specifically by oligomers of N-acetylglucosamine and correlates well with serum total IgE levels (R2 = 0·923). Binding of STA to N-linked glycoproteins (horseradish peroxidase, avidin and IgG) was positive by dot blot and binding assay. As potato lectin activates and degranulates both mast cells and basophils by interacting with the chitobiose core of IgE glycans, higher intake of potato may increase the clinical symptoms as a result of non-allergic food hypersensitivity in atopic subjects.
The CXCR4/CXCL12 (SDF-1) signalling pathway protects non-obese diabetic mouse from autoimmune diabetes
Authors: Aboumrad E , Madec A M , Thivolet C 
Published: August 2010

SummaryChemokines and their receptors are part of polarized T helper 1 (Th1)- and Th2-mediated immune responses which control trafficking of immunogenic cells to sites of inflammation. The chemokine stromal cell-derived factor-1 CXCL-12 (SDF-1) and its ligand the CXCR4 chemokine receptor are important regulatory elements. CXCR4 is expressed on the surface of CD4+ T cells, dendritic cells and B lymphocytes. Levels of CXCR4 mRNA were increased in pancreatic lymph nodes (PLNs) of 4-week-old non-obese diabetic (NOD) mice in comparison to Balb/C mice. However, a significant reduction of CXCR4 was noticed at 12 weeks both at the mRNA and protein levels while expression increased in the inflamed islets. The percentage of SDF-1 attracted splenocytes in a transwell chemotaxis assay was significantly increased in NOD versus Balb/c mice. SDF-1 attracted T cells completely abolished the capacity of diabetogenic T cells to transfer diabetes in the recipients of an adoptive cell co-transfer. When T splenocytes from NOD females treated with AMD3100, a specific CXCR4 antagonist, were mixed with diabetogenic T cells during adoptive cell co-transfer experiments, prevalence of diabetes in the recipients rose from 33% to 75% (P &lt; 0·001). This effect was associated with an increase of interferon (IFN)-γ mRNA and a reduction of interleukin (IL)-4 mRNA levels both in PLNs and isolated islets. AMD3100 also reduced IL-4 and IL-10 production of plate-bound anti-CD3 and anti-CD28-stimulated splenocytes. Immunofluorescence studies indicated that AMD3100 reduced the number of CXCR4+ and SDF-1 positive cells in the inflamed islets. We can conclude that the CXCL-12/CXCR4 pathway has protective effects against autoimmune diabetes.
Chemokine and chemokine receptor analysis reveals elevated interferon-inducible protein-10 (IP)-10/CXCL10 levels and increased number of CCR5+ and CXCR3+ CD4 T cells in synovial fluid of patients with enthesitis-related arthritis (ERA)
Authors: Aggarwal A , Agarwal S , Misra R 
Published: August 2010

Summary
Chemokines and chemokine receptors play a major role in homing of cells to the site of inflammation. Enthesitis-related arthritis (ERA) is a chronic inflammatory arthritis and no data are available on chemokines and their receptors in ERA. Blood (20) and synovial fluid (SF) (11) was collected from patients with ERA, and peripheral blood (PB) was collected from 12 patients with polyarticular juvenile idiopathic arthritis (JIA), nine patients with systemic onset and 18 healthy controls. Chemokines [interleukin (IL)-10/CXCL10, thymus and activation-regulated chemokine (TARC)/CCL17 and regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5] were measured in serum and SF. Chemokine receptor expression was measured by flow cytometry. There was no difference in blood CD4+ T cells bearing CCR5, CCR4 and CXCR3 in ERA and healthy controls. In paired samples the median frequency of CCR5+ CD4+ T cells was higher in SF compared to PB (15·8 versus 3·9%, P &lt; 0·005), as was the frequency of CXCR3+ T cells (21·61% versus 12·46%, P &lt; 0·05). Median serum interferon-inducible protein-10 (IP-10)/CXCL10 levels were higher in patients with ERA compared to controls (139 versus 93 pg/ml; P &lt; 0·05). Further median SF IP-10/CXCL10 levels were higher than the serum levels (2300 pg/ml versus 139 pg/ml; P &lt; 0·01). Serum levels of RANTES/CCL5 were higher in patients (150 ng/ml) compared to control (99 ng/ml; P &lt; 0·01). The SF levels were significantly lower compared to serum (P &lt; 0·05). TARC/CCL17 levels in SF were lower than serum. There is increased homing of CCR5 and CXCR3+ CD4 cells to the SF. Increased SF levels of IP-10/CXCL10 may be responsible for this migration in patients with ERA.
Antibodies to CRMP3–4 associated with limbic encephalitis and thymoma
Authors: Knudsen A , Bredholt G , Storstein A , Oltedal L , Davanger S , Krossnes B , Honnorat J , Vedeler C A 
Published: August 2010

Summary
We present a case with subacute limbic encephalitis (LE) and thymoma. Neither classical onconeural antibodies nor antibodies to voltage gated potassium channels (VGKC) were detected, but the serum was positive for anti-glutamic acid decarboxylase (GAD). The patient serum also stained synaptic boutons of pyramidal cells and nuclei of granule cells of rat hippocampus. The objective of the study was to identify new antibodies associated with LE. Screening a cDNA expression library identified collapsin response mediator protein 3 (CRMP3), a protein involved in neurite outgrowth. The serum also reacted with both CRMP3 and CRMP4 by Western blot. Similar binding pattern of hippocampal granule cells was obtained with the patient serum and rabbit anti-serum against CRMP1–4. The CRMP1–4 antibodies stained neuronal nuclei of a biopsy from the patient's temporal lobe, but CRMP1–4 expression in thymoma could only be detected by immunoblotting. Absorption studies with recombinant GAD failed to abolish the staining of the hippocampal granule cells. Our findings illustrate that CRMP3–4 antibodies can be associated with LE and thymoma. This has previously been associated with CRMP5.
Aberrant activation profile of cytokines and mitogen-activated protein kinases in type 2 diabetic patients with nephropathy
Authors: Wong C K , Ho A W Y , Tong P C Y , Yeung C Y , Kong A P S , Lun S W M , Chan J C N , Lam C W K 
Published: August 2010

Summary
Cytokine-induced inflammation is involved in the pathogenesis of type 2 diabetes mellitus (DM). We investigated plasma concentrations and ex vivo production of cytokines and chemokines, and intracellular signalling molecules, mitogen-activated protein kinases (MAPK) in T helper (Th) cells and monocytes in 94 type 2 diabetic patients with or without nephropathy and 20 healthy controls. Plasma concentrations of inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-18 and chemokine CCL2 in patients with diabetic nephropathy (DN) were significantly higher than control subjects, while IL-10, CXCL8, CXCL9, CXCL10 and adiponectin concentrations of DN were significantly higher than patients without diabetic nephropathy (NDN) and control subjects (all P &lt; 0·05). Plasma concentrations of TNF-α, IL-6, IL-10, IL-18, CCL2, CXCL8, CXCL9, CXCL10 and adiponectin exhibited significant positive correlation with urine albumin : creatinine ratio in DN patients. The percentage increases of ex vivo production of IL-6, CXCL8, CXCL10, CCL2 and CCL5 upon TNF-α activation were significantly higher in both NDN and DN patients than controls (all P &lt; 0·05). The percentage increases in IL-18-induced phosphorylation of extracellular signal-regulated kinase (ERK) in Th cells of NDN and DN were significantly higher than controls (P &lt; 0·05), while the percentage increase in TNF-α-induced phosphorylation of p38 MAPK in monocytes and IL-18-induced phosphorylation of p38 MAPK in Th cells and monocytes were significantly higher in NDN patients than controls. These results confirmed that the aberrant production of inflammatory cytokines and chemokines and differential activation of MAPK in different leucocytes are the underlying immunopathological mechanisms of type 2 DM patients with DN.
Salmonella typhimurium stimulation combined with tumour-derived heat shock proteins induces potent dendritic cell anti-tumour responses in a murine model
Authors: Shilling D A , Smith M J , Tyther R , Sheehan D , England K , Kavanagh E G , Redmond H P , Shanahan F , O'Mahony L 
Published: August 2010

Summary
Appropriate activation of the immune system and effective targeting of tumour cells are the primary hurdles to be overcome for cancer immunotherapy to be successful and applicable to a wide range of tumour types. Our studies have examined the ability of bacterial-stimulated dendritic cells (DCs), loaded with tumour-associated antigens, to inhibit tumour growth in a murine model. Immature murine bone marrow-derived DCs were stimulated in vitro with the cytoplasmic fraction (CM) of Salmonella typhimurium in combination with heat shock proteins (hsps) from 4T1 tumours, isolated using heparin affinity chromatography. Activated DCs were administered subcutaneously. Tumours were generated by orthotopic inoculation of 4T1 cells in Balb/c mice. Primary tumour growth was measured using Vernier calipers, while lung metastases were measured using the clonogenic assay. S. typhimurium CM induced potent tumour necrosis factor (TNF)-α responses from DCs accompanied by significant up-regulation of CD80 and CD86 expression. When injected into mice, bacterial-stimulated DCs loaded with 4T1 hsps inhibited the formation of new 4T1 tumours and reduced the growth rate of established tumours. In addition, the number of lung metastatic nodules was reduced significantly in the DC-treated mice (1·6 ± 0·6 versus 245·9 ± 55·6, P = 0·0015). DCs stimulated with CM alone, exposed to tumour hsps alone or exposed to tumour hsps from an unrelated tumour cell line did not induce a protective immune response. Dendritic cells primed with a proinflammatory bacterial stimulus and tumour-associated antigens induce a protective anti-tumour immune response in this murine model.
Contributions to our understanding of T cell physiology through unveiling the T cell proteome
Authors: Grant M M , Scheel-Toellner D , Griffiths H R 
Published: August 2010

SummarySince the sequencing of the human genome was completed, attention has turned to examining the functionality of the molecular machinery, in particular of protein expression. Differential proteome analysis by two-dimensional electrophoresis has been adopted to study changes in T cell proteomes during T cell activation, and this work is increasing our understanding of the complexity of signals elicited across multiple pathways. The purpose of this review is to summarize the available evidence in the application of proteomic techniques and methodologies to understand T cell receptor activation from lipid raft and cytoskeletal rearrangements, through to signalling cascades, transcription factor modulation and changes in protein expression patterns. These include post-translational modifications, which are not encoded by the genome.
FOXP3 gene expression in a tuberculosis case contact study
Authors: Burl S , Hill P C , Jeffries D J , Holland M J , Fox A , Lugos M D , Adegbola R A , Rook G A , Zumla A , McAdam K P W J , Brookes R H 
Published: August 2010

Summary
Regulatory T lymphocytes (Tregs) that express FOXP3 are involved in the beneficial attenuation of immunopathology, but are also implicated in down-regulation of protective responses to infection. Their role in tuberculosis (TB) is unknown. We classified 1272 healthy TB contacts according to their tuberculin skin test (TST) and interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) results and 128 TB cases, and studied the expression of FOXP3 and interleukin (IL)-10 in blood samples. Compared to the uninfected contact group (TST–, ELISPOT–), we observed higher levels of FOXP3 mRNA in blood from TB patients (&lt; 0·001), but IL-10 expression was slightly lower (P = 0·04). In contrast, FOXP3 expression levels were significantly lower (P = 0·001) in the recently infected contacts (TST+, ELISPOT+) but there was no difference for IL-10 (P = 0·74). We hypothesize that during early/subclinical TB, most of which will become latent, FOXP3+ Tregs may be sequestered in the lungs, but when TB becomes progressive, FOXP3 reappears at increased levels in the periphery. While these findings do not reveal the role, beneficial or harmful, of Tregs in TB, they emphasize the probable importance of these cells.
Levels of CD40 expression on dendritic cells dictate tumour growth or regression
Authors: Murugaiyan G , Martin S , Saha B 
Published: August 2010

SummaryTumour regression requires activation of T cells. It has been shown that the interaction between T cell-expressed CD40-ligand (CD40-L) and antigen-presenting cell-expressed CD40 plays a crucial role in T cell activation. CD40-L- or CD40-deficient mice are susceptible to tumour growth. CD40-based therapies are also shown to control tumour growth significantly, suggesting that CD40–CD40-L interaction induces anti-tumour T cell responses and tumour regression. We demonstrate that the anti-tumour T cell response can be modulated reciprocally as a function of the levels of CD40 expression. At low expression levels, CD40 promotes tumour growth; at higher expression levels, CD40 induces tumour-regressing T cell response. Dendritic cells (DC) sorted onto major histocompatibility complex (MHC)-II expression are found to be similar in CD40 and CD80 expression. The MHC-IIhi/CD40hi DC induce interleukin (IL)-12-dominated and T helper 1 (Th1)-type response, whereas MHC-IIlo/CD40lo DC promote high IL-10 and Th2-type T cells. The T cells induced by these DC also differ in terms of regulatory T cell markers, lymphocyte activation gene-3 (LAG-3) and glucocorticoid-induced tumour necrosis factor (TNF) receptor family-related gene (GITR). Thus, we report for the first time that CD40-induced effector T cell response depends on CD40 expression levels in vivo.
Characterization of the main placental cytokine profiles from HIV-1-infected pregnant women treated with anti-retroviral drugs in France
Authors:   the ANRS 1267 study team and the HIV-1 PMTCT-PlaNet, Faye A , Pornprasert S , Mary J-Y , Dolcini G , Derrien M , Barré-Sinoussi F , Chaouat G , Menu E 
Published: August 2010

SummaryCytokines are involved in regulating HIV-1 infection. They are also placental environment major components. We assessed the potential impact of HIV-1 infection and/or anti-retroviral drugs on the placental cytokine profiles that may be involved in controlling HIV-1 placental dissemination. Placental explants were obtained after elective caesarean section from anti-retroviral-treated HIV-1-infected pregnant women and from HIV-1 non-infected pregnant women. The main placental cytokines were assessed for protein secretion in the supernatants of 24-h placental culture explants and/or in uncultured placental explants for mRNA expression levels. The cytokine profiles were different between the HIV-1-infected and the non-infected groups. Higher medians of leukaemia inhibiting factor (LIF), tumour necrosis factor (TNF)-α and interleukin (IL)-8 secretion were found in the 24-h culture supernatant of term placenta from HIV-1-infected women. High median levels of IL-16 and regulated upon activation normal T cell expressed and secreted (RANTES) levels were found in both groups. The mRNA expression medians were lower for TNF-α and IL-8 and higher for stromal cell-derived factor-1 (SDF-1) in uncultured placental explants from HIV-1-infected women. In the HIV-1-infected group, but not in the non-infected group, the secretion levels of TNF-α and IL-8, as well as their mRNA expression levels, were highly positively correlated; furthermore, their secretion levels were correlated positively with LIF and IL-10 secretion levels. We found no correlation between the cytokine levels and the immunovirological status of the HIV-1-infected mothers or the type or duration of treatment. These results highlight the potential impact of HIV-1 and of the anti-retroviral treatments on the placental cytokines pattern, independently of their anti-viral activity.
Hydroxyurea exerts an anti-proliferative effect on T cells but has no direct impact on cellular activation
Authors: Benito J M , López M , Lozano S , Ballesteros C , González-Lahoz J , Soriano V 
Published: August 2010

SummaryHydroxyurea (HU) is a cytostatic drug which has been used as an anti-HIV agent due mainly to its synergistic activity when combined with certain anti-retrovirals. In addition, HU might have a beneficial effect on parameters involved in the pathogenesis of HIV infection, such as immune activation. To test this hypothesis, the effect of HU on T cell proliferation and T cell activation, as well as the potential association between these two phenomena, were examined in an in vitro model. HU exerted a dose-dependent anti-proliferative effect on T cells, and modulated the expression of different activation markers. In cells exposed to HU, expression of CD25 and CD38 diminished in a dose-dependent manner, whereas expression of CD69 increased. However, when the expression of these markers was examined separately on proliferating and non-proliferating lymphocytes, HU did not exert any significant effect. Thus, the effect of HU on T cell activation is not direct and seems to be mediated through its effect on T cell proliferation.
Dose-dependent synergy of Th1-stimulating cytokines on bacille Calmette–Guérin-induced interferon-γ production by human mononuclear cells
Authors: Chen X , O'Donnell M A , Luo Y 
Published: August 2010

SummarySuccessful bacille Calmette–Guérin (BCG) immunotherapy of bladder cancer depends on the proper induction of a T helper-type 1 (Th1) immune response. In this study we investigated the possible involvement of Th1-stimulating cytokines in BCG-induced interferon (IFN)-γ production as well as their potential roles in enhancing BCG-induced IFN-γ from human peripheral blood mononuclear cells (PBMCs). BCG efficiently induced IFN-γ production by PBMCs in a dose-dependent manner. Neutralization of endogenous cytokines interleukin (IL)-2, IL-12 and IFN-α reduced BCG-induced IFN-γ by 38%, 67% and 49%, respectively. Although single recombinant (r) IL-2, rIL-12 and rIFN-α induced no or a marginal amount of IFN-γ, a combination of any two or three cytokines increased IFN-γ production. When BCG (a subsaturated dose) was combined with mono, dual or triple cytokines, a synergy on IFN-γ production was observed. Such a synergy was readily achievable even when minimal or low doses of cytokines were used. No saturation of IFN-γ production was observed even when a subsaturated BCG dose was combined with very high doses of cytokines. A robust IFN-γ production was also observed when a minimal BCG dose was combined with minimal doses of triple cytokines. In addition, we demonstrated that IL-2- and IFN-α-expressing rBCGs were superior to wild-type BCG for PBMC IFN-γ induction and that combination of both rBCGs showed a synergy in IFN-γ production. Taken together, these results suggest that combination of BCG with certain exogenous or endogenous (expressed by rBCGs) Th1-stimulating cytokines is a rational candidate for further study in bladder cancer treatment.
Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease
Authors: Boyton R J , Altmann D M 
Published: August 2010

SummaryNatural killer cells constitute a potent, rapid part of the innate immune response to infection or transformation, and also generate a link to priming of adaptive immunity. Their function can encompass direct cytotoxicity as well as the release of cytokines and chemokines. In humans, a major component of natural killer (NK) cell target recognition depends mainly on the surveillance of human leucocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIR). Different KIR can transmit inhibitory or activatory signals to the cell, and effector function is considered to result from the balance of these contributing signals. The regulation of NK cell responses depends on a number of variables: KIR genotype, HLA genotype, heterozygosity versus homozygosity for these, whether there is cognate recognition between the HLA and KIR products carried by an individual, clonal variation between individual NK cells in KIR expression, and the specific modulation of HLA expression by infection, transformation or peptide binding. Different HLA/KIR genotypes can impart different thresholds of activation to the NK cell repertoire and such genotypic variation has been found to confer altered risk in a number of diseases including human immunodeficiency virus (HIV) susceptibility and progression, hepatitis C virus clearance, idiopathic bronchiectasis, autoimmunity and cancer.