Biomedical subjects

Anders Elm Pedersen

Publications and source records attributed to Anders Elm Pedersen.

6 recordsLinked to original sources

PubMed2006

[Dendrite cell-based cancer vaccines--clinical application].

Dendritic cell (DC)-based vaccination against cancer is a specific immunotherapy with a new therapeutic approach for patients with cancer. Preclinical and clinical trials, in which more than 1,000 cancer patients received dendritic cell vaccination, have shown that it is possible to activate the immune system against cancer cells and to induce a clinical response in some of the patients. The treatment is so far experimental, and there is a need for well-designed trials that aim to improve the DC vaccine approach.

Cancer Vaccines↗

PubMed2004

Changes in protein expression in p53 deleted spontaneous thymic lymphomas.

By the use of high-resolution two-dimensional gel electrophoresis and computerized image analysis we investigated and compared the expression of cellular proteins from p53 positive (+/+) mouse thymocytes, p53-/- thymocytes before neoplastic transformation, and from cell lines derived from two spontaneous p53-/- thymic lymphomas, SM5 and SM7. A total of around 1500 proteins were detected on individual gels. Only changes in protein expression by a factor of 2 or more were considered. In the thymic lymphoma cells 3-5% of the proteins were found to be differentially regulated when compared with the protein expression in p53+/+ and p53-/- thymocytes. Only a minority (13 proteins) of the quantitatively changed proteins were common for the two thymic lymphoma cell lines, suggesting that the p53 deficiency mainly results in genetic dysfunctions which are individual for a given tumor. Two of the detected proteins increased their expression levels by more than 10 times from the p53+/+ to the p53-/- thymocytes and these high expression levels were also found in thymic lymphomas. The two proteins were identified by mass spectrometry as acidic ribosomal phosphoprotein P0 and a 33-kDa protein with a primary structure containing motifs of the glyoxalase-bleomycin resistance protein family (MDR) as deduced from the cDNA.

Animals↗

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

Demonstration of strong enterobacterial reactivity of CD4+CD25- T cells from conventional and germ-free mice which is counter-regulated by CD4+CD25+ T cells.

Unfractionated CD4+ T cells from the gut-associated lymphoid tissue (GALT) and peripheral lymph nodes are unresponsive when exposed to enterobacterial antigens in vitro. Under similar conditions, CD4+ T cells depleted in vivo or in vitro of CD4+CD25+ T cells proliferate extensively. The CD4+CD25- T cell reactivity depends on MHC class II presentation, specific TCR stimulation, CD4 ligation, and antigen processing by antigen-presenting cells. The CD4+CD25- T cells respond to autologous and heterologous enterobacterial antigens, but not to antigens from the feces of germ-free mice. Surprisingly, CD4+CD25- T cells obtained from the GALT of germ-free mice also proliferate when exposed to enterobacterial antigens, and adding back the conventional or germ-free CD4+CD25+ T cells to the enteroantigen-stimulated CD4+CD25- T cells abolishes proliferation. As judged from carboxyfluorescein diacetate succinimidyl ester-labeling experiments, 4-5% of the CD4+CD25- T cells respond to enteroantigen. The data show for the first time that CD4+CD25- T cells with reactivity towards the enterobacterial flora and regulatory CD4+CD25- T cells are present in both conventional and germ-free mice. The data suggest that a significant proportion of the peripheral pool of CD4+CD25- T cells express anti-enterobacterial reactivity, which, due to the presence of regulatory CD4+CD25+ T cells, is kept in a quiescent state.

Animals↗

PubMed2003

Tumor-associated antigens identified by mRNA expression profiling as tumor rejection epitopes.

Thirteen H-2b-binding peptides derived from six potentially overexpressed proteins in p53-/- thymoma (SM7) cells were studied for immunogenecity and vaccine-induced prevention of tumor growth in mice inoculated with SM7 tumor cells. Six of the peptides generated specific CTL responses after immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth. SM7 inoculated mice treated with a blocking antibody against the inhibitory T cell signal transducing molecule CTLA4 appeared to delay tumor take, suggesting that SM7 thymoma cells are recognized by the adaptive immune system of the host. However, prophylactic vaccination with RAD23-31 and RAD24-31 peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance. Our data would indicate that vaccination with immunogenic peptides derived from potentially overexpressed tumor proteins, as identified by mRNA expression profiling of p53-/- thymoma cells, at best results in a weak tumor protection thus questioning this way of detection of new tumor rejection epitopes.

Journal Article↗

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↗