Biomedical subjects

Mogens Helweg Claesson

Publications and source records attributed to Mogens Helweg Claesson.

6 recordsLinked to original sources

PubMed2006

Chemokines involved in protection from colitis by CD4+CD25+ regulatory T cells.

Chemokines are small proteins involved in the direction of migration of immune cells both during normal homeostasis and inflammation. Chemokines have been implicated in the pathology of many different inflammatory disorders and are therefore appealing therapeutic targets. Using a chemokine/chemokine receptor-specific gene expression profiling system of 67 genes, the authors have determined the expression profile of chemokine and chemokine receptor genes in the rectum of colitic mice and in mice that have been protected fromcolitis by CD4CD25 regulatory T cells. In mice protected from colitis, the authors found down regulation of the mRNA expression of the inflammatory chemokine receptors CCR1 and CXCR3 and their ligands CXCL9, CXCL10, CCL5, and CCL7. Also the transcripts for CCR9, CCL25, CCL17, and CXCL1 are found down regulated in protected compared with colitic animals. In addition, the authors' results suggest that CCL20 is used by CCR6 regulatory T cells in the complex process of controlling colitis because transcripts for this chemokine were expressed to a higher level in protected animals. The chemokine pathways identified in the present study may be of importance for the development of new targets for anti-inflammatory treatment strategies in human inflammatory bowel disease.

Animals↗

PubMed2006

CXC chemokine receptor 3 expression increases the disease-inducing potential of CD4+ CD25- T cells in adoptive transfer colitis.

BACKGROUND: CD4CD25 T cells induce severe colitis when injected into immunodeficient recipients. The migration of disease-inducing cells to the bowel is controlled by adhesion molecules and chemotactic proteins. Chemokine receptors expressed on the T cells are therefore potential targets for anti-inflammatory therapy in inflammatory bowel disease. In this study, we have investigated the role of the chemokine receptor CXCR3 in the development of chronic colitis in a murine model. METHOD: Expression of CXCR3 on CD4 T cell from normal and colitic mice was assessed by flow cytometry. Development of colitis was followed after transfer of either normal or CXCR3CD4CD25T cell into immunodeficient host. In addition, the ability of regulatory T cell to function in vivo in the absence of CXCR3 was tested. RESULTS: We find CXCR3 to be expressed on 80% to 90% of CD4 T cells isolated from colitic mice compared with only 4% to 10% of CD4 T cells in normal naïve mice. Injecting CD4CXCR3CD25 T cells into immunodeficient hosts results in an ameliorated form of colitis with a lack of clinical symptoms, suggesting that CXCR3 expression is important for enteroantigen priming of CD4 T cells and/or subsequent migration into the gut wall. In contrast, CXCR3 expression does not affect the function of regulatory T cells because CXCR3 regulatory T cells are just as capable as their wild-type counterpart of controlling disease development. The diminished disease-inducing capability of CXCR3 T cells is not caused by the absence of enteroantigen specificity; we also tested the enteroantigen-specific proliferative ability of CD4CD25 T cells from CXCR3 mice in vitro and found that they respond even more strongly than wild-type cells. CONCLUSIONS: The present data indicate that CXCR3 plays an important role in controlling the migration of disease-inducing CD4CD25 T cells into the gut wall. In contrast, lack of CXCR3 expression by regulatory T cells does not compromise their function in this model of colitis.

Adoptive Transfer↗

PubMed2005

Colitic scid mice fed Lactobacillus spp. show an ameliorated gut histopathology and an altered cytokine profile by local T cells.

BACKGROUND: Scid mice transplanted with CD4 T blast cells develop colitis. We investigated if the disease was influenced in colitic mice treated with antibiotic and fed Lactobacillus spp. METHODS: Colitic scid mice were treated for 1 week with antibiotics (vancomycin/meropenem) followed or not followed by a 3-week administration of Lactobacillus reuteri DSM-12246 and Lactobacillus rhamnosus 19070-2 at 2x10 live bacteria/mouse/24 hours. After 12 weeks, the rectums were removed for histology, and CD4 T cells from the mesenteric lymph nodes (MLN) were polyclonally activated for cytokine measurements. RESULTS: Irrespective of no treatment or treatments with antibiotics and probiotics, all mice transplanted with T cell blasts lost 10% of their body weight during the 12-week experimental period, whereas the nontransplanted mice had a 10% weight increase (P<0.001). All mice treated with antibiotics but not fed probiotics showed severe gut inflammation, whereas only 2 of the 7 mice fed probiotics showed signs of severe colitis (P<0.05). MLN-derived CD4 T cells from this latter group of mice showed lower levels of interleukin-4 secretion (P<0.05) and a tendency to higher interferon-gamma production than mice not fed probiotics. CONCLUSIONS: Our data suggest that probiotics added to the drinking water may ameliorate local histopathological changes and influence local cytokine levels in colitic mice but not alter the colitis-associated weight loss.

Animal Feed↗

PubMed2004

Induction of regulatory dendritic cells by dexamethasone and 1alpha,25-Dihydroxyvitamin D(3).

Dendritic cells (DC) modulated to induce T cell hyporesponsiveness have promising potential in immunotherapy of autoimmune disorders and for the prevention of allograft rejection. While studying the effect of immunosuppressive agents on the maturation of DC we found that 1alpha,25-Dihydroxyvitamin D(3) the active form of Vitamin D(3) (D(3)) in combination with dexamethasone (Dex) has a synergistic effect on LPS-induced maturation of DC. Monocyte-derived DCs cultured with D(3) and Dex during LPS-induced maturation have a low stimulatory effect on allogeneic T cells comparable with that of immature DCs. But in contrast to immature DCs, D3/Dex exposed DCs secrete IL-10 and show upregulated transcription of mRNA encoding the Ig-like inhibitory receptor ILT4. D3/Dex exposed DCs also inhibit alloreactivity and slightly enhance the degree of apoptosis in mature DCs. Thus, D(3)/Dex is an effective immunosuppressive drug combination for the induction of DCs capable of inducing T cell hyporesponsiveness.

Anti-Inflammatory Agents↗

PubMed2004

Identifying multiple tumor-specific epitopes from large-scale screening for overexpressed mRNA.

The rationale of a T-cell epitope-based approach to cancer treatment is primarily rooted in the hypothesis that CD8(+) cytotoxic T cells (CTLs) can be manipulated to specifically identify and kill cancer cells. A solid understanding of CTL specificity and activation is a fundamental requirement for tumor immunotherapy. The means to identify tumor-specific CTL epitopes and to monitor corresponding CTL responses are important enabling technologies. Recent advances in these enabling technologies include their ability to exploit genomic, transcriptomic and proteomic information. These advances constitute new opportunities, which will enable approaches to tumor immunotherapy that encompass both human diversity and tumor heterogeneity, increase the efficacy of tumor immunotherapy and potentially provide the opportunity for individualized therapy.

Epitopes, T-Lymphocyte↗

PubMedDate not supplied

Dendritic cells in peripheral tolerance and immunity.

Dendritic cells capable of influencing immunity exist as functionally distinct subsets, T cell-tolerizing and T cell-immunizing subsets. The present paper reviews how these subsets of DCs develop, differentiate and function in vivo and in vitro at the cellular and molecular level. In particular, the role of DCs in the generation of regulatory T cells is highlighted.

Animals↗