PubMed Health⌕ Search

Biomedical subjects

Jens F Dahlerup

Publications and source records attributed to Jens F Dahlerup.

7 recordsLinked to original sources
PubMed2006

[CD4 + CD25 + regulatory T cells and their importance to human illnesses].

Regulatory T cells ensure a balanced immune response that is competent both to fight pathogens, at the same time, to recognize self-antigens and commensals as harmless. Regulatory mechanisms are essential in preventing autoimmune disorders but may also facilitate the progression of malignant diseases and the establishment of latent infections via suppression of the host immune response. Regulatory T cells arise in the thymus, and regulatory T cell function can be induced in the periphery, so-called infectious tolerance. An absolute or relative defect in regulatory T cell function may contribute to the development of autoimmune disorders such as rheumatoid arthritis, type 1 diabetes mellitus, multiple sclerosis and chronic inflammatory bowel disease. Regulatory T cell therapy is a tempting strategy for reestablishing the immune balance and thus preventing or reversing these disorders. Reestablishment of the immune balance may be accomplished by adoptive transfer of ex vivo-propagated regulatory T cells or by induction of regulatory functions locally in the organs, although such strategies are in their infancy in human research.

Autoimmune Diseases↗
PubMed2004

Increased production of granulocyte-macrophage colony-stimulating factor in Crohn's disease--a possible target for infliximab treatment.

BACKGROUND: The presence of neutrophils among epithelial cells is one of the major features of the inflammation in Crohn's disease, and has been used to indicate disease activity. The survival of neutrophils outside the blood vessels is limited and their longevity is influenced by granulocyte-macrophage colony-stimulating factor (GM-CSF), which probably reduces neutrophil apoptosis. OBJECTIVE: To study GM-CSF production in intestinal cell cultures from Crohn's disease patients before and after infliximab treatment. PATIENTS: Colonic mucosal biopsies were obtained from 29 Crohn's disease patients before and after three infliximab infusions (5 mg/ml) and from ten healthy subjects. METHODS: Biopsies were cultured in RPMI at high concentrations of interleukin-2 (IL-2) (2000 U/ml) and IL-4 (500 U/ml), but without antigen addition. GM-CSF content was analysed after 5 days culture and related to the Crohn's disease activity index (CDAI) and compared with the GM-CSF production from healthy subjects. Peripheral leucocyte count, C-reactive protein and the degree of mucosal inflammation, evaluated histologically, were determined. In-vitro T cell GM-CSF production was studied with/without addition of infliximab and after stimulation. RESULTS: GM-CSF production was increased in Crohn's disease patients compared with healthy controls (P = 0.02) and correlated with the CDAI (Spearman rho = 0.65, P = 0.001). GM-CSF levels and mucosal histology score decreased (P = 0.007 and P = 0.01 respectively) after three infliximab infusions, as did the peripheral blood leucocyte count (P < 0.001). Infliximab inhibited in-vitro T cell GM-CSF production. CONCLUSION: In-vitro cell culture production of GM-CSF was increased in Crohn's disease and related to inflammation, but decreased after infliximab treatment, probably because intestinal T cell GM-CSF production was reduced.

Adolescent↗
PubMed2003

The effect of etanercept and infliximab on the production of tumour necrosis factor alpha, interferon-gamma and GM-CSF in in vivo activated intestinal T lymphocyte cultures.

BACKGROUND/AIMS: Infliximab (Ifx) is effective in the treatment of Crohn's disease (CD) and rheumatoid arthritis (RA), etanercept (Eta) in RA but not in CD. The mechanisms underlying these clinical differences are not fully understood, but this knowledge could be valuable to identify responders and develop new treatments. This study compares Eta and Ifx in vitro regarding transmembrane tumour necrosis factor alpha (tmb-TNF-alpha) expression and interferon-gamma (IFN-gamma), TNF-alpha and granulocyte macrophage colony stimulating factor (GM-CSF) production in intestinal T lymphocytes. METHODS: T lymphocyte cultures were established from biopsies from 10 CD patients and three healthy controls. The cytokine production and the expression of tmb-TNF-alpha were measured in the presence of Ifx/Eta. RESULTS: Eta and Ifx downregulated the production of IFN-gamma and GM-CSF in colonic T lymphocytes from CD patients and healthy controls. Both drugs bound tmb-TNF-alpha on activated T lymphocytes besides neutralising TNF-alpha, Eta less efficiently than Ifx (406 pg/ml (337-475); 133 pg/ml (119-147); p=0.004). TNF-alpha was detectable with the present assay in cell lines cultured in the presence of excess Eta. CONCLUSIONS: We have established that Eta is just as efficient as Ifx in downregulating IFN-gamma and GM-CSF production in vitro and Eta bound to tmb-TNF-alpha. However, Eta bound the TNF-alpha molecule, important in CD, less efficiently than Ifx.

Antibodies, Monoclonal↗
PubMed2002

T-cell vaccination in Crohn's disease: principles and presentation of the first two cases.

In Crohn's disease (CD) CD4(+) T-cells producing tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) are important for disease progression. T-cell vaccination with such attenuated (gamma-irradiated) CD4(+) T cells may ameliorate the auto-reactive actions of Type-1 T cells through stimulation of interleukin-10 (IL-10)-producing regulatory T cells. This study aimed to propagate and use gut-derived type-1 CD4(+) T-cells for vaccination in CD. In a case study, two patients with CD-activity index (CDAI) >150 for >1 year were vaccinated with 800 x 10(6) attenuated autologous gut-derived CD4(+) T cells producing Type-1 cytokine -- grown in the presence of high concentrations of only IL-2 and IL-4. The T-cell vaccination was safe, causing only minor redness and tenderness at the injection sites. In Case 2, the treatment brought 3-years with active steroid-resistant CD into remission. CDAI dropped from 171 to 76, CD-endoscopic index of severity fell from 20 to eight and C-reactive protein reduced from 165 to 70 nmol/L. Case 1 received rescue infliximab (there was disease progression before sufficient quantities of cells were ready for the second vaccination). We concluded that it is possible to propagate T cells for autologous vaccination for CD and that treatment was safe. One patient, vaccinated according to the protocol, improved with sustained result for >1 year.

Adult↗