Burning mouth syndrome (BMS), a chronic diffuse oral pain syndrome affecting ∼1% of the general population, is diagnosed when explanatory oral pathology and other identifiable causes are absent. BMS has been recognized for decades, but its etiology remains unknown and has not previously been attributed to mast cell disease. Three ...

J Oral Pathol Med (2011) Background:  Perforin and granzyme B (GB) are the main constituents of cytotoxic T-lymphocyte granules, and they have important roles in preventing the initiation and progression of cancer. Methods:  The aim of this study was to compare the expression of CD8(+) /perforin(+) double-staining and GB(+) cells, ...

Tolerance to food antigen manifests in the absence and/or suppression of antigen-specific immune responses locally in the gut but also systemically, a phenomenon known as oral tolerance. Oral tolerance is thought to originate in the gut-draining lymph nodes, which support the generation of FoxP3(+) regulatory T (Treg) cells. Here we ...

Trogocytosis describes the transfer of surface determinants between immune cells and has been implicated in immune regulation. Most findings are based on in vitro studies since in vivo trogocytosis of immune cells is difficult to detect under physiological conditions. We used low frequencies of memory P14 T cells to demonstrate ...

The tumor suppressor adenomatous polyposis coli (APC) is a multifunctional protein that not only inhibits the Wnt signaling pathway by promoting the degradation of β-catenin but also controls cell polarity, motility, and division. APC is abundantly expressed in the adult central nervous system, but its role in adult neurogenesis remains ...

Adaptive immunity is characterized by the expansion of an Ag-specific T cell population following Ag exposure. The precise mechanisms, however, that control the expansion and subsequent contraction in the number of Ag-specific T cells are not fully understood. We show that T cell/transmembrane, Ig, and mucin (TIM)-4, a receptor for ...

Immunological synapses (ISs) are formed at the T cell-antigen-presenting cell (APC) interface during antigen recognition, and play a central role in T-cell activation and in the delivery of effector functions. ISs were originally described as a peripheral ring of adhesion molecules surrounding a central accumulation of T-cell receptor (TCR)-peptide major ...

Recognition of drugs by immune cells is usually explained by the hapten model, which states that endogenous metabolites bind irreversibly to protein to stimulate immune cells. Synthetic metabolites interact directly with protein-generating antigenic determinants for T cells; however, experimental evidence relating intracellular metabolism in immune cells and the generation of ...

Antigen-presenting cells (APCs) play a crucial role in the induction of immune responses. However, the optimal administration route of tumor-specific APCs for inducing effective immunological responses via cancer immunotherapy remains to be elucidated. Human NKT cells are known to have strong anti-tumor activities and are activated by the specific ligand, ...

Human adipocyte precursor cells (APC) have been characterized in their proliferation and differentiation potential from subcutaneous, omental, and mesenteric depots, mostly from morbidly obese patients. Cells from the preperitoneal adipose compartment have not been characterized yet, least of all when obtained from normal weight subjects. The aim was to compare ...

During T-cell migration, cell polarity is orchestrated by chemokine receptors and adhesion molecules and involves the functional redistribution of molecules and organelles towards specific cell compartments. In contrast, it is generally believed that the cell polarity established when T cells meet antigen-presenting cells (APCs) is controlled by the triggered T-cell ...

Cell proliferation is accompanied by an increase in the utilization of glucose and glutamine. The proliferative response is dependent on a decrease in the activity of the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)-Cdh1 which controls G1-to-S-phase transition by targeting degradation motifs, notably the KEN box. This occurs not only in cell ...

BACKGROUND: Oligodeoxynucleotides (ODNs) containing unmethylated cytosine-guanosine (CpG) sequence motifs constitute the immunostimulatory components of bacterial DNA which potently activate innate immunity. Administration of CpG-ODNs before the onset of experimental colitis prevents intestinal inflammation by induction of colitis-suppressing T cells. AIMS: To identify the interplay between innate and adaptive immune cells ...

Activated protein C (aPC) therapy reduces mortality in adult patients with severe sepsis. In mouse endotoxemia and sepsis models, mortality reduction requires the cell signaling function of aPC, mediated through protease-activated receptor-1 (PAR1) and endothelial protein C receptor (EPCR; also known as Procr). Candidate cellular targets of aPC include vascular ...

The innate immune receptors, such as Toll-like receptors (TLRs), are intimately involved in the early sensing of invading microorganisms or their structural components. Engagement of TLRs with their ligands results in activation of several downstream intracellular pathways leading to activation of innate and adaptive immune system cells. It was initially ...

The immunomodulatory effect of Schistosoma mansoni antigens has often been attributed to interaction with PRR expressed on APC. Our previous work has shown that S. mansoni-soluble egg antigen (SEA) can induce, together with a Th2 response, TGF-β-dependent Foxp3 expression in naïve CD4(+) T cells from NOD mice. We found that ...

Full activation and differentiation of resting T cells into effector T cells requires at least two signals, the first through engagement of the T cell antigen receptor (TCR) by the antigen-major histocompatibility complex (MHC) on antigen-presenting cells (APCs), and the second by engagement of co-stimulatory molecules such as CD28, on ...

The objective of this study was to access APC-effector cell cluster formation in genetically susceptible BALB/c (H-2(d) ) mice infected with highly virulent Moscow strain of ectromelia virus (ECTV-MOS) and estimate of lymphocyte activation based upon expression of CD62L and CD44 molecules. APC-effector cell clusters were obtained by enzymatic digestion ...

CD40L on CD4(+) T cells plays a vital role in the activation of antigen-presenting cells, thus catalyzing a positive feedback loop for T-cell activation. Despite the pivotal juxtaposition of CD40L between antigen-presenting cells and T-cell activation, only a T-cell receptor stimulus is thought to be required for early CD40L surface ...

CD40 is mainly expressed by professional antigen-presenting cells (APCs). Its ligand, CD40L, is transiently expressed on activated CD4(+) T-cells. CD40-CD40L interactions mediate T-cell help to APCs and provide crucial signals for affinity maturation and B-cell class switching. In mammals, agonistic monoclonal anti-CD40 antibodies (mAbs) mimic the effects of CD40L on ...

Stimulation of toll-like receptor-9 by CpG oligodeoxynucleotides (CpG-ODN) has been shown to counteract the immunosuppressive microenvironment and to inhibit tumor growth in glioma models. These studies, however, have used high doses of CpG-ODN, which can induce toxicity in a clinical setting. The goal of this study was to evaluate the ...

Absence of lymph nodes in nonmammalian species, expression of MHCII by APCs in the periphery, and the recent findings that T cells can change their polarization status after presentation in the lymph nodes imply a role for MHCII-mediated presentation outside the organized lymphoid tissue. This study shows that MHCII(+) ECs ...

We have recently shown that Skp2 levels are high in undifferentiated human embryonic stem cells, but decline rapidly following induction of differentiation, thereby leading to accumulation of p27. Changes in Skp2 levels were found to be caused mainly by its rate of degradation. Here we show that the activity of ...

CD4(+) T cells recognize peptides displayed by MHC II molecules on the surface of specialized antigen-presenting cells (APCs). These peptides are generally considered to come from exogenous proteins that have been internalized by APCs and degraded in the endocytic network, thus representing a snapshot of proteins in the APC's extracellular ...

Here, we demonstrate that hepatic stellate cells (HSC) isolated from Lewis rats have in vitro antigen-presentation cell (APC) functionality and are able to process and present exogenous antigens. We show activation of a major histocompatibility complex II (RT1BI)-restricted T-cell hybridoma specific for guinea pig myelin basic protein (gpMBP) after coculture ...

TLR9 is expressed in cells of the innate immune system, as well as in B lymphocytes and their progenitors. We investigated the effect of the TLR9 ligand CpG DNA on the proliferation of pro-B cells. CpG DNA inhibits the proliferation of pro-B, but not pre-B, cells by inducing caspase-independent cell ...

CD4(+) T cell recognition of MHC:peptide complexes in the context of a costimulatory signal results in the large-scale redistribution of molecules at the T cell-APC interface to form the immunological synapse. The immunological synapse is the location of sustained TCR signaling and delivery of a subset of effector functions. T ...

Apc, a negative regulator of the canonical Wnt signaling pathway, is a bona-fide tumor suppressor whose loss of function results in intestinal polyposis. APC is located in a commonly deleted region on human chromosome 5q, associated with myelodysplastic syndrome (MDS), suggesting that haploinsufficiency of APC contributes to the MDS phenotype. ...

Human natural killer (NK) cells express Toll-like receptor 9 (TLR9) transcript and, upon exposure to microbial CpG oligodeoxynucleotide (ODN), release cytokines and kill target cells. Here we show that NK cell treatment with CpG ODN results in down-modulation of KIR3DL2 inhibitory receptor from the cell surface and in its cointernalization ...

The first issue in selecting a system for antigen-presentation experiments is to define the appropriate type of antigen-presenting cell (APC) to study. For some experiments, crude preparations such as splenocytes or peripheral blood mononuclear cells (PBMCs) may suffice to provide APC function for stimulating T cells. This unit develops approaches ...

For over three decades now, the T cell receptor (TCR) for antigen has not ceased to challenge the imaginations of cellular and molecular immunologists alike. T cell antigen recognition transcends every aspect of adaptive immunity: it shapes the T cell repertoire in the thymus and directs T cell-mediated effector functions ...

PURPOSE: Antigen (Ag)-presenting cells (APCs) participate in the development of allergic conjunctivitis (AC). However, the conjunctival APCs that take up Ag in AC have not been identified. We sought to clarify the phenotypes of conjunctival APCs that take up, process, and present Ag to T cells during the development of ...

The activation of classical alphabeta T cells is initiated when the T cell receptor (TCR) recognizes peptide antigens presented by major histocompatibility complex (pMHC) molecules. This recognition always occurs at the junction of a T cell and antigen-presenting cell (APC). Existing models of T-cell activation accurately explain the sensitivity and ...

CD4+ T cells engage different activating cells during their generation in the bone marrow and thymus and during their homeostasis and activation in the periphery. During these processes, T cells or their precursors establish a molecular platform for communication in the interface between the two cells that is called immune ...

Quyn and colleagues report that gut stem cells have a biased spindle orientation and asymmetric retention of label-retaining DNA. These features are lost in mouse and human tissues when the microtubule binding protein Apc is mutated. In the developing kidney, Apc acts downstream from primary cilium signaling to influence spindle ...

BACKGROUND: One to three percent of patients exposed to intravenously injected iodinated contrast media (CM) develop delayed hypersensitivity reactions. Positive patch test reactions, immunohistological findings, and CM-specific proliferation of T cells in vitro suggest a pathogenetic role for T cells. We have previously demonstrated that CM-specific T cell clones (TCCs) ...

We investigated the roles of specific subsets of donor APCs purified from bone marrow in donor T cell activation and graft-vs-leukemia (GvL) activity in murine models of hemopoietic stem cell transplantation. Lineage(-)CD11c(+) APC precursors were separated from donor bone marrow based on expression of CD11b. Transplanting lineage(-)CD11c(+)CD11b(-) APC (CD11b(-) APC) ...

The initiation of T-cell immune responses requires professional antigen-presenting cells. Emerging data point towards an important role for macrophages (Mphi) in the priming of naïve T cells. In this study we analyzed the efficiency and the mechanisms by which Mphi derived from spleen (Sp-Mphi) or bone marrow (BM-Mphi) present Lymphocytic ...

Nanomaterials improve everyday products but their safety for human health is poorly known. In this study we explored immunological effects of five different nanomaterials on antigen presenting cells (APC) in vitro. Nanomaterials studied were rutile titanium dioxide (TiO2), amorphous silica-coated rutile titanium dioxide (TiO2-silica), zinc oxide (ZnO), single-walled carbon nanotubes ...

Synthetic oligonucleotides containing CpG motifs have been shown to induce proliferation, differentiation, and cytokine production in B cells, macrophages, and dendritic cells through a TLR9-dependent mechanism. A class (CpG-A) and B class (CpG-B) oligonucleotides display distinct physical properties. CpG-A, but not CpG-B, can multimerize to form exceedingly large lattices. CpG-A ...

GRAIL (gene related to anergy in lymphocytes), is an E3 ubiquitin ligase with increased expression in anergic CD4+ T cells. The expression of GRAIL has been shown to be both necessary and sufficient for the induction of T cell (T) anergy. To date, several subsets of anergic T cells have ...

B lymphocytes are a potential alternative to dendritic cell immunotherapy, with the advantages of relative abundance in peripheral blood and the ability to function as APCs. Although B cells express multiple receptors that induce costimulatory molecules, B cell vaccine studies have focused primarily on CD40 stimulation. To optimize the potential ...

During adaptive immune responses, T lymphocytes recognize antigenic peptides presented by MHC molecules on antigen-presenting cells (APCs). This recognition results in the formation of a so-called immune synapse (IS) at the T-cell/APC interface, which is crucial for T-cell activation. The molecular composition of the IS has been extensively studied, but ...

It is recognized that functional activities of antigen-presenting cells (APCs) in mucosal tissue sites differ from those of systemic APCs; however, it is unknown whether there are further differences between APC populations residing in different mucosal sites. In this study, we directly compared murine CD11c+ APCs isolated from colon, lung, ...

Apc mutations cause intestinal tumorigenesis through Tcf4 activation. However, direct techniques for studying Tcf4 activation in vivo are limited. Here, we describe the development of a Tcf4-GFP reporter mouse model for directly studying Tcf4 activation. We first developed a GFP reporter construct (Tcf4-GFP) and transfected it into SW480 cells that ...

As a model to dissect the effects of CpG-oligonucleotides (CpG) on rituximab (RTX)-mediated therapeutic killing of autoimmune or malignant B lymphocytes, nude mice were grafted with Daudi human B cells. These mice were then injected with RTX alone or together with CpG. The human B cell aggregate was measured, and ...

BACKGROUND: Sublingual immunotherapy (SLIT) is safe and reduces both symptoms and medication requirements in patients with type I respiratory allergies. Nonetheless, immune mechanisms underlying SLIT need to be further documented. OBJECTIVE: A detailed characterization of the lingual immune system was undertaken in mice, to investigate the presence of tolerogenic and ...

Th1 cell responses to the variant surface glycoprotein (VSG) of African trypanosomes play a critical role in controlling infection through the production of IFN-gamma, but the role of APCs in the induction and regulation of T cell-mediated protection is poorly understood. In this study, we have investigated the Ag presentation ...

OBJECTIVE: Trauma-hemorrhage results in depressed immune responses of antigen-presenting cells (APCs) and T-cells. Recent studies suggest a key role of depressed T-cell derived interferon (IFN)-g in this complex immune cell interaction. The aim of this study was to elucidate further the underlying mechanisms responsible for dysfunctional T-cells and their interaction ...

Adult stem cells define a cellular reserve with the unique capacity to replenish differentiated cells of a tissue throughout an organism's lifetime. Previous analysis has demonstrated that the adult Drosophila midgut is maintained by a population of multipotent intestinal stem cells (ISCs) that resides in epithelial niches. Adenomatous polyposis coli ...