Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Helge Scott is active.

Publication


Featured researches published by Helge Scott.


Gastroenterology | 1998

Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease

Ellen M. Nilsen; Frode L. Jahnsen; Knut E.A. Lundin; Finn-Eirik Johansen; Olav Fausa; Ludvig M. Sollid; Jørgen Jahnsen; Helge Scott; Per Brandtzaeg

BACKGROUND & AIMS Celiac disease appears to be a T cell-mediated enteropathy induced by gluten in genetically predisposed individuals. Duodenal biopsy specimens from patients with celiac disease and histologically normal controls were investigated to see if cytokine expression is related to disease activity. METHODS Cytokine messenger RNA (mRNA) expression was determined by quantitative reverse-transcription polymerase chain reaction and in situ expression by immunohistochemistry. RESULTS In normal controls, mRNA levels were usually below the quantitative limit, even after in vitro gluten stimulation. By contrast, interferon (IFN)-gamma mRNA was increased more than 1000-fold in untreated disease. In vitro gluten stimulation of specimens from treated patients (gluten-free diet) increased IFN-gamma mRNA to the levels of untreated patients. In addition, increased mRNA levels for interleukin (IL)-2, IL-4, IL-6, and tumor necrosis factor alpha were found after such stimulation, whereas mRNA for IL-5, IL-10, and IL-12p40 was usually below the quantitative level. Biopsy specimens from untreated patients contained on average 10-fold more lamina propria cells positive for IFN-gamma than normal controls, whereas cells containing IL-4 were rare in both subject groups. CONCLUSIONS The results show that mucosal gluten exposure in patients with celiac disease rapidly elicits high levels of IFN-gamma expression and lower levels of IL-2, IL-4, IL-6, and tumor necrosis factor alpha even in the virtual absence of IL-12.


Gut | 1995

Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Th1 or Th0 profile dominated by interferon gamma.

Ellen M. Nilsen; Knut E.A. Lundin; P. Krajci; Helge Scott; Ludvig M. Sollid; Per Brandtzaeg

Coeliac disease is precipitated in susceptible subjects by ingestion of wheat gluten or gluten related prolamins from some other cereals. The disease is strongly associated with certain HLA-DQ heterodimers, for example, DQ2 (DQ alpha 1*0501, beta 1*0201) in most patients and apparently DQ8 (DQ alpha 1*0301, beta 1*0302) in a small subset. Gluten specific T cell clones (TCC) from coeliac intestinal lesions were recently established and found to be mainly restricted by HLA-DQ2 or HLA-DQ8. Antigen induced production of cytokines was studied in 15 TCC from three patients, 10 being DQ2 and five DQ8 restricted. Cell culture supernatants were prepared by stimulation with gluten peptides in the presence of DQ2+ or DQ8+ Epstein-Barr virus transformed B cells as antigen presenting cells (APC). Supernatants were analysed for cytokines by bioassays, ELISA, and CELISA. Cellular cytokine mRNA was analysed semi-quantitatively by slot blotting and polymerase chain reaction (PCR). All TCC were found to secrete interferon (IFN) gamma, often at high concentrations (> 2000 U/ml); some secreted in addition interleukin (IL) 4, IL 5, IL 6, IL 10, tumour necrosis factor (TNF), and transforming growth factor (TGF) beta. The last TCC thus displayed a Th0-like cytokine pattern. However, other TCC produced IFN gamma and TNF but no IL 4, or IL 5, compatible with a Th1-like pattern. In conclusion, most DQ8 restricted TCC seemed to fit with a Th0 profile whereas the DQ2 restricted TCC secreted cytokines more compatible with a Th1 pattern. The TCC supernatants induced upregulation of HLA-DR and secretory component (poly-Ig receptor) in the colonic adenocarcinoma cell line HT-29.E10, most probably reflecting mainly the high IFN gamma concentrations. This cytokine, particularly in combination with TNF alpha, might be involved in several pathological features of the coeliac lesion. The characterised cytokine profiles thus support the notion that mucosal T cells activated in situ by gluten in a DQ restricted fashion play a central part in the pathogenesis of coeliac disease.


Scandinavian Journal of Immunology | 1989

Intraepithelial T Cells of the TcRγ/δ+CD8− and Vδ1/Jδ1+ Phenotypes are Increased in Coeliac Disease

Trond S. Halstensen; Helge Scott; Per Brandtzaeg

Expression of the γ/δ T‐Cell receptor (TcR) for antigen on CD3+ intraepithelial lymphocytes (IEL) was studied in situ by two‐colour immunofluorescence on jejunal tissue secretions from 24 patients with coeliac disease and 17 controls. The proportion of intraepithelial TcRγ/δ+ cells was significantly increased (P<0.002) in untreated (median 20%, range 11–53%) as well in treated (gluten‐free diet) coeliac disease (median 23%, range 16–55%) compared with controls (median 2%, range 0–39%). Although TcRγ/β+ IEL dominated both in controls and coeliac disease. T cells expressing the TcRα/δ were preferentially located within the epithelium rather than in the lamina propria. Paired staining for TcRγ/δ and CD8 revealed that most (∼90%) intraepithelial TcRγ/δ+ lymphocytes in coeliac disease were CD8−. A remarkably large fraction (median 67%, range 58–94%) of intraepithelial TcRγ/δ+ cells expressed the Vδ1/Jδ1‐encoded epitope revealed by monoclonal antibody δTCS1. Our results suggested that increase of the intraepithelial TcRγ/δ+ CD8− subset of T cells is particularly related to coeliac disease.


Gut | 1994

Increased macrophage subset in inflammatory bowel disease: apparent recruitment from peripheral blood monocytes.

J Rugtveit; Per Brandtzaeg; Trond S. Halstensen; Olav Fausa; Helge Scott

Mucosal specimens from active Crohns disease (ileum, n = 6; colon, n = 6), active ulcerative colitis (n = 9), normal ileum (n = 6), and normal colon (n = 6) were subjected to paired immunofluorescence staining for characterisation of macrophage subsets in situ. In the normal state, only few CD68+ macrophages (< 10%) expressing the myelomonocytic L1 antigen (calprotectin) were seen. In inflamed mucosa, especially near small vessels, the CD68+L1+ fraction increased with the degree of inflammation, near ulcers to median 65% (range 35-91%). Cells reactive with the monoclonal antibody RFD7 were also increased in inflammation but less than 5% of them costained for L1 antigen. It is concluded that L1 producing macrophages are distinct from the RFD7+ subset and probably recently recruited from peripheral blood monocytes. Like granulocytes, L1+ macrophages may be important in non-specific defence, providing calprotectin with putative anti-microbial and anti-proliferative properties.


American Journal of Transplantation | 2002

The Impact of Cytomegalovirus Infection and Disease on Rejection Episodes in Renal Allograft Recipients

Solbjørg Sagedal; Knut P. Nordal; Anders Hartmann; Ståle Sund; Helge Scott; Miklos Degré; Aksel Foss; Torbjørn Leivestad; Kåre Osnes; Per Fauchald; Halvor Rollag

Cytomegalovirus (CMV) infection and disease are potential risk factors for acute allograft rejection in renal transplant recipients. The present study specifically addresses this issue. From October 1994 to July 1997, 477 consecutive renal allograft recipients (397 first transplants and 80 retransplants) were included in the study. CMV infection (cytomegalovirus pp65 antigen in leukocytes) and disease (infection and clinical symptoms or signs of disease) were examined prospectively for 3 months. No CMV prophylaxis was given, and CMV disease was treated with intravenous (i.v.) ganciclovir. The retransplantation of four patients transplanted twice during the study and 22 patients receiving kidneys from human leucocyte antigen (HLA)‐identical siblings were excluded from statistical analysis. Rejections were evaluated clinically [277(61%)] and 173 (38%) also had a biopsy verified rejection. CMV infection occurred in 64% of the patients and 24% experienced CMV disease. In a multiple time‐dependent Cox analysis, CMV infection and CMV disease were independent significant predictors for clinical acute rejections, RR = 1.6 (1.1–2.5, p = 0.02) and RR = 2.5 (1.2–5.1, p = 0.01), respectively. Among 173 patients with biopsy verified rejection, 72% of the patients had tubulointerstitial rejection whereas 28% had a vascular rejection. CMV disease, but not CMV infection was a predictor of tubulointerstitial rejection, RR = 3.1 (1.1–9.3, p = 0.04). CMV infection and disease are independent risk factors for clinical acute rejection in kidney allograft recipients. CMV disease is an independent risk factor for biopsy verified acute tubulointerstitial rejection in kidney allograft recipients.


PLOS Medicine | 2004

The Molecular Basis for Oat Intolerance in Patients with Celiac Disease

Helene Arentz-Hansen; Burkhard Fleckenstein; Øyvind Molberg; Helge Scott; Frits Koning; Günther Jung; Peter Roepstorff; Knut E.A. Lundin; Ludvig M. Sollid

ABSTRACT Background Celiac disease is a small intestinal inflammatory disorder characterized by malabsorption, nutrient deficiency, and a range of clinical manifestations. It is caused by an inappropriate immune response to dietary gluten and is treated with a gluten-free diet. Recent feeding studies have indicated oats to be safe for celiac disease patients, and oats are now often included in the celiac disease diet. This study aimed to investigate whether oat intolerance exists in celiac disease and to characterize the cells and processes underlying this intolerance. Methods and Findings We selected for study nine adults with celiac disease who had a history of oats exposure. Four of the patients had clinical symptoms on an oats-containing diet, and three of these four patients had intestinal inflammation typical of celiac disease at the time of oats exposure. We established oats-avenin-specific and -reactive intestinal T-cell lines from these three patients, as well as from two other patients who appeared to tolerate oats. The avenin-reactive T-cell lines recognized avenin peptides in the context of HLA-DQ2. These peptides have sequences rich in proline and glutamine residues closely resembling wheat gluten epitopes. Deamidation (glutamine→glutamic acid conversion) by tissue transglutaminase was involved in the avenin epitope formation. Conclusions We conclude that some celiac disease patients have avenin-reactive mucosal T-cells that can cause mucosal inflammation. Oat intolerance may be a reason for villous atrophy and inflammation in patients with celiac disease who are eating oats but otherwise are adhering to a strict gluten-free diet. Clinical follow-up of celiac disease patients eating oats is advisable.


Gastroenterology | 1997

Cytokine profiles differ in newly recruited and resident subsets of mucosal macrophages from inflammatory bowel disease

Jarle Rugtveit; Ellen M. Nilsen; Arne Bakka; Hege S. Carlsen; Per Brandtzaeg; Helge Scott

BACKGROUND & AIMS Most macrophages in the normal intestinal mucosa have a mature phenotype. In inflammatory bowel disease (IBD), a monocyte-like subset (CD14+ L1+) accumulates. The aim of this study was to characterize its potential with regard to cytokines. METHODS Lamina propria mononuclear cells were adherence-separated, with or without depletion of CD14+ cells, and production of cytokines was investigated by bioassay, enzyme-linked immunosorbent assay, or immunocytochemistry. RESULTS Tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-1 receptor antagonist were found mainly in cells positive for myelomonocytic L1. In undepleted IBD cultures, TNF-alpha, IL-1alpha and beta, and IL-10 were markedly up-regulated by pokeweed mitogen stimulation; IL-1alpha and beta and IL-10 were also up-regulated by stimulation of interferon gamma and lipopolysaccharide in combination. The latter stimulation had no effect on normal control or CD14-depleted IBD cultures. Indomethacin caused a marked increase of TNF-alpha, particularly in undepleted IBD cultures, whereas IL-10 and IL-4 decreased TNF-alpha and IL-1beta in both CD14+ and CD14 macrophages. CONCLUSIONS In IBD mucosa, macrophages with a monocyte-like phenotype are primed for production of TNF-alpha and IL-1alpha/beta and may therefore be of significant pathogenic importance [corrected]. However, this CD14+ subset, as well as the mucosal resident macrophages, have preserved responsiveness to several down-regulatory factors such as the macrophage deactivators IL-10 and IL-4.


Human Immunology | 1994

T cells from the small intestinal Mucosa of a DR4, DQ7/DR4. DQ8 celiac disease patient preferentially recognize gliadin when presented by DQ8

Knut E.A. Lundin; Helge Scott; Olav Fausa; Erik Thorsby; Ludvig M. Sollid

CD is an immunologic disease of the small intestine which is precipitated by ingestion of wheat gliadin. Most patients carry the HLA-DQ (alpha 1*0501, beta 1*0201) (DQ2) heterodimer. We recently reported that a preponderance of gliadin-specific T cells from the small intestinal mucosa of DQ2-positive CD patients were restricted by this DQ heterodimer. However, a small percentage of CD patients do not carry this DQ heterodimer, and most of them instead carry DQ (alpha 1*0301, beta 1*0302) (DQ8). Here we report that a majority of gliadin-specific T cells from the small intestinal mucosa of a DR4,DQ7/DR4,DQ8 heterozygous CD patient are restricted by DQ8. Thus, preferential presentation of gliadin-derived peptides to T cells by the CD-associated DQ2 and DQ8 molecules may be an initial and important immunopathogenic step in CD.


American Journal of Pathology | 2008

Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenic or proinflammatory activation.

Axel M. Küchler; Jürgen Pollheimer; Johanna Balogh; Jon Sponheim; Linda Manley; Dag R. Sorensen; Paula M. De Angelis; Helge Scott; Guttorm Haraldsen

Interleukin (IL)-33 is a novel member of the IL-1 family of cytokines that promotes Th2 responses in lymphocytes as well as the activation of both mast cells and eosinophils via the ST2 receptor. Additionally, IL-33 has been proposed to act as a chromatin-associated transcriptional regulator in both endothelial cells of high endothelial venules and chronically inflamed vessels. Here we show that nuclear IL-33 is expressed in blood vessels of healthy tissues but down-regulated at the earliest onset of angiogenesis during wound healing; in addition, it is almost undetectable in human tumor vessels. Accordingly, IL-33 is induced when cultured endothelial cells reach confluence and stop proliferating but is lost when these cells begin to migrate. However, IL-33 expression was not induced by inhibiting cell cycle progression in subconfluent cultures and was not prevented by antibody-mediated inhibition of VE-cadherin. Conversely, IL-33 knockdown did not induce detectable changes in either expression levels or the cellular distribution of either VE-cadherin or CD31. However, activation of endothelial cell cultures with either tumor necrosis factor-alpha or vascular endothelial growth factor and subcutaneous injection of these cytokines led to a down-regulation of vascular IL-33, a response consistent with both its rapid down-regulation in wound healing and loss in tumor endothelium. In conclusion, we speculate that the proposed transcriptional repressor function of IL-33 may be involved in the control of endothelial cell activation.


Scandinavian Journal of Immunology | 1980

HLA‐DR‐like Antigens in the Epithelium of the Human Small Intestine

Helge Scott; B. G. Solheim; Per Brandtzaeg; Erik Thorsby

Sections of ethanol‐fixed, paraffin‐embedded tissue specimens from different parts of the human gastrointestinal tract were stained by an indirect immunofluorescence method with a rabbit antiserum to HLA‐DR‐antigens from B lymphocytes. A specific staining reaction was seen in a patchy pattern apically in the columnar cells of the normal small intestine, decreasing in intensity from the top of the villi towards the crypts. No HLA‐DR‐like antigens could he detected in colon or stomach epithelium, whereas cellS with the morphology of lymphocytes and histiocytes in the lamina propria and also capillary walls were specifically stained throughout the gastrointestinal tract.

Collaboration


Dive into the Helge Scott's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Erik H. Strøm

Oslo University Hospital

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge