Search results for "CD40"
showing 10 items of 122 documents
Tc9 cells, a new subset of CD8+T cells, support Th2-mediated airway inflammation
2013
Similar to T-helper (Th) cells, CD8(+) T cells also differentiate into distinct subpopulations. However, the existence of IL-9-producing CD8(+) T (Tc9) cells has not been elucidated so far. We show that murine CD8(+) T cells activated in the presence of IL-4 plus TGF-β develop into transient IL-9 producers characterized by specific IFN-γ and IL-10 expression patterns as well as by low cytotoxic function along with diminished expression of the CTL-associated transcription factors T-bet and Eomesodermin. Similarly to the CD4(+) counterpart, Tc9 cells required for their differentiation STAT6 and IRF4. Tc9 cells deficient for these master regulators displayed increased levels of Foxp3 that in t…
Functionally Active T Cell Receptor/CD3 Complexes Are Present at the Surface of Cloned Cytotoxic T Cells without Fluorescence-Immunological Detectabi…
1996
The cytotoxic T cell clone 10BK.1 is activated in response to the ovalbumin peptide OVA257-264 in a major histocompatibility complex class I-restricted manner. Following activation 10BK.1 cells proliferate, secrete lymphokines, and kill syn- and allogeneic target cells. Using immunofluorescence analysis we detected CD8, LFA-1, and ICAM-1 on the surface of 10BK.1 cells, but no CD3 or T cell receptor (TCR). In contrast, the proliferative response of 10BK.1 cells to antigen was efficiently blocked by soluble antibodies directed at CD3 epsilon or TCR alpha beta, but not by antibodies directed at TCR gamma delta. In addition, lysis of target cells was blocked by F(ab')2 fragments of antibodies d…
Genome wide identification of new genes and pathways in patients with both autoimmune thyroiditis and type 1 diabetes
2015
Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340…
The RNA binding protein tristetraprolin influences the activation state of murine dendritic cells
2010
Abstract Dendritic cells (DCs) serve to maintain peripheral tolerance under steady state conditions. Upon triggering by activation signals they initiate strong immune responses. The activation of DCs is accompanied by a rapid upregulation of proinflammatory cytokines, which were shown in other cell types to be regulated by mechanisms at the transcriptional and posttranscriptional level. Tristetraprolin (TTP), an important RNA binding protein, is involved in the regulation of mRNA stability of such cytokines. In this study we analyzed the significance of TTP for mouse DCs, which were derived from TTP −/− and WT bone marrow progenitor cells (BM-DCs). Unstimulated BM-DCs of TTP −/− mice expres…
Release of IL-12 by dendritic cells activated by TLR ligation is dependent on MyD88 signaling, whereas TRIF signaling is indispensable for TLR synerg…
2010
Abstract Synergistic activation of dendritic cells by combinations of TLR ligands requires both MyD88- and TRIF-dependent signaling. Recently, it has been shown that certain combinations of TLR ligands act in synergy to induce the release of IL-12 by DCs. In this study, we sought to define the critical parameters underlying TLR synergy. Our data show that TLR ligands act synergistically if MyD88- and TRIF-dependent ligands are combined. TLR4 uses both of these adaptor molecules, thus activation via TLR4 proved to be a synergistic event on its own. TLR synergy did not affect all aspects of DC activation but enhanced primarily the release of certain cytokines, particularly IL-12, whereas the …
Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells.
1996
Abstract BACKGROUND & AIMS: Inflammatory liver disease as well as rejection of liver allografts are thought to be mediated by resident antigen- presenting cells in the liver. At the same time, in vivo antigen presentation in the liver appears to be a more tolerogenic than systemic antigen challenge. The aim of this study was to show and characterize the antigen-presenting capability of sinusoidal endothelial cells and Kupffer cells. METHODS: Purified murine sinusoidal endothelial cells and Kupffer cells were studied for their ability to serve as accessory cells and antigen-presenting cells by proliferation assays. They were also studied for their expression of interleukin 1 and the B7 costi…
Phenotypic characterisation of pro-inflammatory monocytes and dendritic cells in peripheral arterial disease
2012
SummaryAtherosclerosis is a chronic inflammatory process involving antigen-presenting cells like monocytes and dendritic cells (DC). The aim of this study was to perform a phenotypic characterisation of these cell types in patients with different degrees of peripheral arterial disease (PAD). Sixty patients with PAD [N= 30 intermittent claudication (IC), N= 30 critical limb ischemia (CLI)] and 30 controls were included. Peripheral blood leucocytes were analysed from peripheral blood by flow cytometry using different gating strategies to directly identify and analyse monocytes, myeloid DC, (mDC) and plasmacytoid DC (pDC). PAD patients showed a significantly higher proportion of proinflammator…
CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db/db mice
2018
Abstract Aims CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia. Methods and results Male wild type and CD40L−/− mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks. Weight, cholesterol, HDL, and LDL levels, endothelial function (isometric tension recording), oxidative stress (NADPH oxidase expression, dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide synthase, interleukin-6 expression) were assessed. CD40L exp…
Reactive plasmacytoses are expansions of plasmablasts retaining the capacity to differentiate into plasma cells.
1999
Abstract Circulating plasma cells in 10 cases of reactive plasmacytosis had a shared phenotype with early plasma cell (CD19+CD38+ CD138+ CD40+CD45+ CD11a+ CD49e−CD56−). In most cases, a minor subpopulation of CD28+ plasma cells was also detected. Reactive plasma cells were highly proliferative, suggesting the presence of circulating progenitors (plasmablasts). After CD138+ plasma cell removal, highly proliferative CD138− plasmablasts differentiated into CD138+ plasma cells within a few days. This differentiation, which was associated with increased CD38 and decreased HLA-DR expression, was further confirmed by a large increase in intracellular Ig content (associated with Ig secretion) and w…
Uptake of microparticle-adsorbed protein antigen by bone marrow-derived dendritic cells results in up-regulation of interleukin-1α and interleukin-12…
1995
Dendritic cells synthesize and express major histocompatibility complex (MHC) class II peptide-binding elements constitutively and, therefore, belong to the category of professional antigen-presenting cells. Unlike other cells that show constitutive class II expression, such as B cells and certain T cell clones, dendritic cells possess the unique capacity to activate naive T cells. Using dendritic cells generated in vitro by culture of mouse bone marrow in the presence of low doses of recombinant mouse granulocyte/macrophage colony-stimulating factor, we found that discrete maturation stages of these cells can be distinguished which were correlated with defined functional capabilities. The …