Search results for "Dendritic Cell"

2014

The maturation status of dendritic cells determines whether interacting T cells are activated or if they become tolerant. Previously we could induce T cell tolerance by applying a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor (HMGCRI) atorvastatin, which also modulates MHC class II expression and has therapeutic potential in autoimmune disease. Here, we aimed at elucidating the impact of this therapeutic strategy on T cell differentiation as a consequence of alterations in dendritic cell function. We investigated the effect of HMGCRI during differentiation of peripheral human monocytes and murine bone marrow precursors to immature DC in vitro and assessed their phenotype. To …

Excessive CpG 1668 stimulation triggers IL-10 production by cDC that inhibits IFN-alpha responses by pDC.

2008

Upon stimulation with a wide range of concentrations of CpG oligodeoxynucleotide 2216 (CpG 2216), plasmacytoid DC are induced to produce type I IFN (IFN-alpha/beta). In contrast, CpG 1668 shows a bell-shaped dose-response correlation, i.e. only intermediate but not high doses of CpG 1668 induce IFN-alpha/beta. Interestingly, high-dose CpG 1668 completely inhibited IFN-alpha responses induced by CpG 2216. Experiments using supernatant of high-dose CpG-1668-treated cells indicated that secreted inhibitor(s) mediated the IFN-alpha shut-off. Among modulating cytokines, IL-10 turned out to be one important negative regulator. In line with this, supernatants of IL-10-deficient DC cultures stimula…

Virally Infected Mouse Liver Endothelial Cells Trigger CD8+ T-Cell Immunity

2009

Background & Aims Dendritic cell activation through ligation of pattern recognition receptors leading to full functional maturation causes induction of CD8 + T-cell immunity through increased delivery of costimulatory signals instead of tolerance. Here we investigate whether organ-resident antigen-presenting cells, such as liver sinusoidal endothelial cells (LSECs), also switch from tolerogenic to immunogenic CD8 + T-cell activation upon such stimulation. Methods Murine LSECs were isolated by immunomagnetic separation and analyzed for functional maturation upon triggering pattern recognition receptors or viral infection employing gene expression analysis and T cell coculture assays. In vivo…

Myeloid dendritic cell: From sentinel of immunity to key player of peripheral tolerance?

2009

Myeloid dendritic cells (DC) are "sentinels" of immunity, ideally positioned throughout the body gateways and equipped with unique properties to transport antigens from the periphery to lymphoid tissues. They are professional antigen-presenting cells transmitting incoming infectious signals to T cells, the key players of adaptive immunity. For induction of effective antigen-specific T-cell immunity, crosstalk of DC and naive T cells is mandatory. However, besides this essential immunostimulatory function of DC, consolidated findings from the DC research field in the last 10 years have shown that DC have an additional important function. They act as pivotal players in the peripheral toleranc…

Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naïve T cells, and favors expansion of regulatory T ce…

2007

AbstractRetroviruses have developed immunmodulatory mechanisms to avoid being attacked by the immune system. The mechanisms of this retrovirus-associated immune suppression are far from clarified. Dendritic cells (DCs) have been attributed a decisive role in these pathogenic processes. We have used the Friend retrovirus (FV) mouse model in order to acquire further knowledge about the role of infection of DCs in virus-induced immunosuppression. About 20% of the myeloid DCs that were generated from the bone marrow of FV-infected mice carried FV proteins. The infection was productive, and infected DCs transmitted the virus in cell culture and in vivo. FV infection of DCs led to a defect in DC …

Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated au…

2012

AbstractAntineutrophil cytoplasmic antibodies (ANCAs) target proteins normally retained within neutrophils, indicating that cell death is involved in the autoimmunity process. Still, ANCA pathogenesis remains obscure. ANCAs activate neutrophils inducing their respiratory burst and a peculiar form of cell death, named NETosis, characterized by formation of neutrophil extracellular traps (NETs), decondensed chromatin threads decorated with cytoplasmic proteins endorsed with antimicrobial activity. NETs have been consistently detected in ANCA-associated small-vessel vasculitis, and this association prompted us to test whether the peculiar structure of NET favors neutrophil proteins uploading i…

IL-17 promotes progression of cutaneous leishmaniasis in susceptible mice.

2009

Abstract Resistance to leishmaniasis in C57BL/6 mice depends on Th1/Tc1 cells. BALB/c mice preferentially develop Th2 immunity and succumb to infection. We now assessed the role of IL-17 in cutaneous leishmaniasis. During the course of Leishmania major infection, BALB/c CD4 cells and neutrophils produced increased amounts of IL-17 as compared with cells from C57BL/6 mice. This increase was associated with significantly increased IL-23 release from L. major-infected BALB/c dendritic cells (DC), whereas IL-6 and TGF-β1 production by BALB/c and C57BL/6 DC were comparable. Interestingly, lesion sizes in infected IL-17-deficient BALB/c mice were dramatically smaller and failed to progress as com…

Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses

2008

AbstractThe tyrosine kinase inhibitors sorafenib and sunitinib are approved for the treatment of patients with malignant diseases. To analyze the possible use of these compounds in combination with immunotherapeutic approaches, we analyzed the effects of both inhibitors on the immunostimulatory capacity of human dendritic cells (DCs) and the induction of primary immune responses in vivo. Sorafenib, but not sunitinib, inhibits function of DCs, characterized by reduced secretion of cytokines and expression of CD1a, major histocompatibility complex, and costimulatory molecules in response to TLR ligands as well as by their impaired ability to migrate and stimulate T-cell responses. These inhib…

A dendritic cell tumor in an HIV-infected patient: case report

2009

First results for resetting the antitumor immune response by immune corrective surgery in colon cancer.

1998

BACKGROUND: A critical step for cancer recurrence is the failure of the cellular immune response. It is suspected that chronic humoral immune responses against some tumor-associated antigens (TAA) can contribute to that failure. METHODS: In this study, we tested the ability of an immune corrective surgical procedure to prevent recurrences of colon cancer in stages I, II, and III. Radiolabeled anti-TAG antibodies injected intravenously become concentrated on TAG-72 immune complexes presented by follicular dendritic cells, which are responsible for the persistent humoral response against TAG-72 TAA. Using a hand-held gamma probe, we can intraoperatively detect and remove lymph nodes involved …