Search results for " Present"
showing 10 items of 566 documents
Monitoring of anti-vaccine CD4 T cell frequencies in melanoma patients vaccinated with a MAGE-3 protein.
2005
Abstract Quantitative evaluation of T cell responses of patients receiving antitumoral vaccination with a protein is difficult because of the large number of possible HLA-peptide combinations that could be targeted by the response. To evaluate the responses of patients vaccinated with protein MAGE-3, we have developed an approach that involves overnight stimulation of blood T cells with autologous dendritic cells loaded with the protein, sorting by flow cytometry of the T cells that produce IFN-γ, cloning of these cells, and evaluation of the number of T cell clones that secrete IFN-γ upon stimulation with the Ag. An important criterion is that T cell clones must recognize not only stimulat…
A CD40/CD40L feedback loop drives the breakdown of CD8+T-cell tolerance following depletion of suppressive CD4+T cells
2014
Dendritic cells (DCs) are the key APCs not only for the priming of naive T cells, but also for the induction and maintenance of peripheral T-cell tolerance. We have recently shown that cognate interactions between Foxp3(+) Tregs and steady-state DCs are crucial to maintain the tolerogenic potential of DCs. Using DIETER mice, which allow the induction of antigen presentation selectively on DCs without altering their maturation status, we show here that breakdown of CD8(+) T-cell tolerance, which ensues after depletion of suppressive CD4(+) T cells, is driven by a positive feedback loop in which autoreactive CD8(+) T cells activate DCs via CD40. These data identify ligation of CD40 on DCs as …
Use of CD64 for the diagnosis of sepsis: a case-control study.
2010
CD64 is the high-affinity receptor of IgG. It is upregulated by inflammatory cytokines on neutrophils. The upregulation of CD64 is linked with PMN activation in SIRS or sepsis. Our aim is to verify these correlations.
Differential expression of alternative H2-M isoforms in B cells, dendritic cells and macrophages by proinflammatory cytokines.
1999
Major histocompatibility (MHC) class II heterodimers bind peptides generated by degradation of endocytosed antigens and display them on the surface of antigen presenting cells (APCs) for recognition by CD4+ T cells. Efficient loading of MHC class II molecules with peptides is catalyzed by the MHC class II-like molecule H2-M. The coordinate regulation of MHC class II and H2-M expression is a prerequisite for efficient MHC class II/peptide assembly in APCs determining both the generation of the T cell repertoire in the thymus and cellular immune responses in the periphery. Here we show that expression of H2-M and MHC class II genes is coordinately and cell type-specific regulated in splenic B…
H2-M, a facilitator of MHC class II peptide loading, and its negative modulator H2-O are differentially expressed in response to proinflammatory cyto…
2000
H2-M is a major histocompatibility complex (MHC) class II-like molecule that catalyzes peptide binding to MHC class II molecules. Recently, the H2-O heterodimer, encoded by H2-Oa and H2-Ob in the MHC class II region, has been shown to be physically associated with H2-M in B cells and to downregulate H2-M function. Examination of H2-O expression in freshly isolated mouse organs revealed that H2-Oa- and H2-Ob-specific transcripts are present in both lymphoid and nonlymphoid tissues. To evaluate the gene regulation and functional impact of H2-O on antigen presentation, we examined the effects on MHCII, invariant chain (Ii), H2-M, and H2-O gene expression of interleukin (IL)-4, IL-10, and inter…
Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompati…
2002
To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal alphaDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c- cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When alphaDEC-205:OVA was injected subcutaneously, OVA protein was identified over a …
Tumor-Derived Lactic Acid Modulates Dendritic Cell Activation and Differentiation.
2004
Abstract The tumor milieu can influence DC differentiation in vivo and in vitro. We analyzed DC differentiation in a 3-dimensional tumor model and propose a new mechanism of DC modulation by the tumor environment. Monocytes were cultured in the presence of IL-4 and GM-CSF within multicellular tumor spheroids (MCTS) generated from urothelial carcinoma (J82, UMUC3) and melanoma cell lines (MelIm, Mel108). Monocytes invaded the tumor spheroids and differentiated into tumor-associated dendritic cells (TADC) that displayed an altered phenotype compared to DC generated without tumor contact. The expression of CD1a was reduced on TADC whereas CD80, CD86 and CD16 were upregulated. In addition, TADC…
T-Cell Epitope Processing (The Epitope Flanking Regions Matter)
2009
Epitopes presented by major histocompatibility complex (MHC) class I molecules for cytotoxic T-lymphocyte (CTL) recognition are derived mainly from cytosolic proteins. Antigen presentation on the cell surface requires correct processing of epitopes by the proteasome, cytosolic and endoplasmic reticulum (ER) aminopeptidases, efficient TAP transport, and sufficient binding to MHC class I molecules. The efficiency of the epitope generation depends not only on the epitope itself but also on its flanking regions. To investigate preferences at the C-terminal epitope extension on processing and presentation, the SIINFEKL (S8L) epitope can be used as a model epitope. By exchanging the amino acids a…
Activity of the dietary flavonoid, apigenin, against multidrug-resistant tumor cells as determined by pharmacogenomics and molecular docking
2015
Apigenin is a common dietary flavonoid with considerable cytotoxic activity in vitro and in vivo. Despite many mechanistic studies, less is known about resistance factors hampering apigenin's activity. We investigated the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5. Multidrug-resistant cells overexpressing these ABC transporters were not cross-resistant toward apigenin. Moreover, apigenin inhibited not only P-glycoprotein but also BCRP by increasing cellular uptake of doxorubicin and synergistic inhibition of cell viability in combination with doxorubicin or docetaxel in multidrug-resistant cells. To perform in silico molecular docki…
Allorestricted T lymphocytes with a high avidity T-cell receptor towards NY-ESO-1 have potent anti-tumor activity.
2009
The cancer-testis antigen NY-ESO-1 has been targeted as a tumor-associated antigen by immunotherapeutical strategies, such as cancer vaccines. The prerequisite for a T-cell-based therapy is the induction of T cells capable of recognizing the NY-ESO-1-expressing tumor cells. In this study, we generated human T lymphocytes directed against the immunodominant NY-ESO-1(157-165) epitope known to be naturally presented with HLA-A*0201. We succeeded to isolate autorestricted and allorestricted T lymphocytes with low, intermediate or high avidity TCRs against the NY-ESO-1 peptide. The avidity of the established CTL populations correlated with their capacity of lysing HLA-A2-positive, NY-ESO-1-expre…