Biomedical subjects

C Zelle-Rieser

Publications and source records attributed to C Zelle-Rieser.

4 recordsLinked to original sources

PubMed2001

Mannosylated lipoarabinomannans inhibit IL-12 production by human dendritic cells: evidence for a negative signal delivered through the mannose receptor.

IL-12 is a key cytokine in directing the development of type 1 Th cells, which are critical to eradicate intracellular pathogens such as Mycobacterium tuberculosis. Here, we report that mannose-capped lipoarabinomannans (ManLAMs) from Mycobacterium bovis bacillus Calmette-Guérin and Mycobacterium tuberculosis inhibited, in a dose-dependent manner, the LPS-induced IL-12 production by human dendritic cells. The inhibitory activity was abolished by the loss of the mannose caps or the GPI acyl residues. Mannan, which is a ligand for the mannose receptor (MR) as well as an mAb specific for the MR, also inhibited the LPS-induced IL-12 production by dendritic cells. Our results indicate that ManLAMs may act as virulence factors that contribute to the persistence of M. bovis bacillus Calmette-Guérin and M. tuberculosis within phagocytic cells by suppressing IL-12 responses. Our data also suggest that engagement of the MR by ManLAMs delivers a negative signal that interferes with the LPS-induced positive signals delivered by the Toll-like receptors.

Carbohydrate Sequence↗

PubMed2001

A clinically approved oral vaccine against pneumotropic bacteria induces the terminal maturation of CD83+ immunostimulatory dendritic cells.

Dendritic cells (DCs) are important antigen-presenting cells of the immune system that have attracted interest as cellular adjuvants to induce immunity in clinical settings. We have investigated the effects of Broncho-Vaxom, an oral vaccine composed of lysates from eight pneumotropic bacteria, on human monocyte-derived dendritic cells (moDCs). Broncho-Vaxom induced the terminal maturation of CD83+ moDCs. MoDCs stimulated with Broncho-Vaxom displayed a phenotype of activated DCs with high levels of major histocompatibility complex (MHC) molecules and increased levels of adhesion and co-stimulatory molecules. In addition, moDCs activated with Broncho-Vaxom exhibited enhanced T cell-stimulatory capacity in the allogeneic mixed leukocyte reaction. Broncho-Vaxom at 100 microg/ml was as potent as TNF-alpha at 1000 U/ml in activating human moDCs. Neither LPS-like activity nor bacterial DNA was found to be responsible for the maturation-inducing activity of Broncho-Vaxom, suggesting that Broncho-Vaxom contains other bacterial factors that are capable of inducing the terminal maturation of moDCs. In DC-based immunotherapy, Broncho-Vaxom could be used as a stimulus of DC maturation, which meets the standards of good manufacturing practice (GMP). In addition, vaccination with Broncho-Vaxom-loaded moDCs may be an attractive treatment option in preventing recurrent airway infection in predisposed individuals.

Adjuvants, Immunologic↗

PubMed2001

The disabled dendritic cell.

Dendritic cells are important antigen-presenting cells of the immune system that induce and modulate immune responses. They interact with T and B lymphocytes as well as with natural killer cells to promote activation and differentiation of these cells. Dendritic cells generated in vitro from monocytes by use of the cytokines GM-CSF and IL-4 are increasingly used clinically to enhance antitumor immunity in cancer patients. However, recent studies revealed that the functional repertoire of monocyte-derived dendritic cells may be incomplete. Important functions of monocyte-derived dendritic cells such as migration or the ability to induce natural killer cell activation or type 2 T helper cell differentiation appear to be impaired. We propose that all these deficiencies relate to a single biochemical deficiency of monocyte-derived dendritic cells. IL-4, which is used to generate monocyte-derived dendritic cells, suppresses phospholipase A2, the enzyme that liberates arachidonic acid from membrane phospholipids and contributes to the synthesis of platelet-activating factor. Monocyte-derived dendritic cells must therefore fail to generate platelet-activating factor as well as arachidonic acid derivatives such as prostaglandins, leukotrienes, and lipoxins, collectively referred to as eicosanoids. Since eicosanoids and platelet-activating factor are known to play an important role in processes such as leukocyte migration, natural killer cell activation, and type 2 T helper cell differentiation, the deficiency in eicosanoid and platelet-activating factor biosynthesis may be responsible for the observed handicaps of monocyte-derived dendritic cells.

Antigen-Presenting Cells↗

PubMed2001

Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma.

PURPOSE: The 32 to 44 kDa. oncofetal antigen-immature laminin receptor (OFA-iLR) is a multifunctional protein expressed by various tumors, including breast, lung, ovary and prostate carcinoma as well as lymphoma. OFA-iLR has been implicated in tumor invasiveness, metastasis and growth. Interferon-gamma producing effector T cells and interleukin (IL)-10 producing suppressor T cells specific for OFA-iLR have been described. MATERIALS AND METHODS: The 43515 IgG2a anti-OFA-iLR monoclonal antibody was used to detect OFA-iLR expression in human renal cell carcinoma tissue by flow cytometry and immunoblotting. Spontaneous or therapy induced immune responses against OFA-iLR were determined in patients with metastatic renal cell carcinoma. Proliferative and cytokine (interferon-gamma and IL-10) responses of peripheral blood mononuclear cells from patients with renal cell carcinoma against recombinant OFA-iLR were assessed. RESULTS: Using flow cytometry OFA-iLR was detected in all 13 tumors tested. Immunoblotting revealed differences in OFA-iLR expression in renal cell carcinoma and normal kidney tissue. OFA-iLR specific proliferative and cytokine responses of mononuclear cells were detected in all 6 patients tested. Importantly evidence was also obtained that treating metastatic renal cell carcinoma with tumor lysate pulsed dendritic cells would enhance OFA-iLR specific immunity. CONCLUSIONS: This study demonstrates that OFA-iLR is an immunogenic tumor associated antigen in human renal cell carcinoma. OFA-iLR specific effector T cells producing interferon-gamma may have a role in the control of tumor growth, whereas suppressor T cells producing IL-10 may promote tumor tolerance and, thus, tumor progression.

Antigens, Neoplasm↗