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Immune Cell Functions (immune + cell_function)
Selected AbstractsImmune cell function testing: an adjunct to therapeutic drug monitoring in transplant patient managementCLINICAL TRANSPLANTATION, Issue 2 2003Richard Kowalski Abstract:, Each year, 55 000 organ transplants are performed worldwide. Cumulatively, the number of living organ recipients is now estimated to be over 300 000. Most of these transplant recipients will remain on immunosuppressive drugs for the remainder of their lives to prevent rejection episodes. Controlled doses of these drugs are required to prevent over-medication, which may leave the patient susceptible to opportunistic infection and drug toxicity effects, or under-dosing, which may lead to shortened graft survival because of rejection episodes. This paper describes the result of a multicenter study conducted at the Universities of Pittsburgh, Alabama and Maryland to evaluate an in vitro assay (CylexTM Immune Cell Function Assay) for the measurement of global immune response in transplant patients receiving immunosuppressive therapy. The assay uses a whole blood sample to maintain the presence of the drug during incubation. Following overnight incubation of blood with phytohemagglutinin (PHA), CD4 cells are selected using paramagnetic particles coated with a monoclonal antibody to the CD4 epitope. The CD4-positive cells are targeted as major immunosuppressive drugs are designed to specifically inhibit T-cell activation which has been implicated in rejection. The data generated at these three sites were submitted in support of an Food and Drug Association (FDA) application for the use of this assay in the detection of cell-mediated immunity in an immunosuppressed population. The assay was cleared by the FDA on April 2, 2002. This cross-sectional study was designed to establish ranges for reactivity of this bioassay in the assessment of functional immunity for an individual solid organ recipient at any point in time. [source] Cell contact interaction between adipose-derived stromal cells and allo-activated T lymphocytesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2009Monique E. Quaedackers Abstract Mesenchymal stromal cells regulate immune cell function via the secretion of soluble factors. Cell membrane interactions between these cell types may play an additional role. Here, we demonstrate that subpopulations of allo-activated T cells are capable of binding to human adipose-derived stromal cells (ASC). The bound T-cell population contained CD8+ T cells and was enriched for CD4,CD8, T cells, whereas the proportion of CD4+ T cells was decreased compared with the non-bound T-cell population. Bound CD4+ T cells had high proliferative activity and increased CD25 and FoxP3 expression. However, they also expressed CD127, excluding regulatory T-cell function. In CD8+ T cells, IL-2 sensitivity, as determined by the analysis of phosphorylated STAT5, was lower in the presence of ASC and even lower in bound cells. In contrast, IL-2-induced phosphorylated STAT5 levels were higher in bound CD4+ T cells than in non-bound CD4+ T cells. Additionally, pro-proliferative TGF-, signalling via endoglin and SMAD1/5/8 phosphorylation was detected in bound CD4+ T cells. Even after prolonged co-culture with ASC, the activated phenotype of bound CD4+ T cells persisted. In conclusion, these results demonstrate that the binding of lymphocytes to ASC represents an immunomodulatory mechanism in which CD8+ T cells are inhibited in their responsiveness to pro-inflammatory stimuli and reactive CD4+ T cells are depleted from the immune response. [source] Somatostatin receptors and autoimmune-mediated diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2005Xaio-Ping Wang Abstract Somatostatin (SST) peptide is produced by various SST-secreting cells throughout the body and acts as a neurotransmitter or paracrine/autocrine regulator in response to ions, nutrients, peptides hormones and neurotransmitters. SST is also widely distributed in the periphery to regulate the inflammatory and immune cells in response to hormones, growth factors, cytokines and other secretive molecules. SST peptides are considered the most important physiologic regulator of the islet cell, gastrointestinal cell and immune cell functions, and the importance of SST production levels has been implicated in several diseases including diabetes. The expression of SST receptors has also been found in T lymphocytes and primary immunologic organs. Interaction of SST and its receptors is also involved in T-cell proliferation and thymocyte selection. SSTR gene-ablated mice developed diabetes with morphologic, physiologic and immunologic alterations in the endocrine pancreas. Increased levels of mononuclear cell infiltration of the islets are associated with the increased levels of antigen-presenting cells located in the islets and peripancreatic lymph nodes. Increased levels of SST were also found in antigen-presenting cells and are associated with a significant increase of CD8 expression levels on CD4+/CD8+ immature thymocytes. These findings highlight the crucial role of this neuroendocrine peptide and its receptors in regulating autoimmune functions. Copyright © 2004 John Wiley & Sons, Ltd. [source] Reversible translocation of p115-RhoGEF by G12/13 -coupled receptorsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2008Bruno H. Meyer Abstract G protein-coupled receptors (GPCRs) are important targets for medicinal agents. Four different G protein families, Gs, Gi, Gq, and G12, engage in their linkage to activation of receptor-specific signal transduction pathways. G12 proteins were more recently studied, and upon activation by GPCRs they mediate activation of RhoGTPase guanine nucleotide exchange factors (RhoGEFs), which in turn activate the small GTPase RhoA. RhoA is involved in many cellular and physiological aspects, and a dysfunction of the G12/13 -Rho pathway can lead to hypertension, cardiovascular diseases, stroke, impaired wound healing and immune cell functions, cancer progression and metastasis, or asthma. In this study, regulator of G protein signaling (RGS) domain-containing RhoGEFs were tagged with enhanced green fluorescent protein (EGFP) to detect their subcellular localization and translocation upon receptor activation. Constitutively active G,12 and G,13 mutants induced redistribution of these RhoGEFs from the cytosol to the plasma membrane. Furthermore, a pronounced and rapid translocation of p115-RhoGEF from the cytosol to the plasma membrane was observed upon activation of several G12/13 -coupled GPCRs in a cell type-independent fashion. Plasma membrane translocation of p115-RhoGEF stimulated by a GPCR agonist could be completely and rapidly reversed by subsequent application of an antagonist for the respective GPCR, that is, p115-RhoGEF relocated back to the cytosol. The translocation of RhoGEF by G12/13 -linked GPCRs can be quantified and therefore used for pharmacological studies of the pathway, and to discover active compounds in a G12/13 -related disease context. J. Cell. Biochem. 104: 1660,1670, 2008. © 2008 Wiley-Liss, Inc. [source] Alcohol and Hepatitis C Virus,Interactions in Immune Dysfunctions and Liver DamageALCOHOLISM, Issue 10 2010Gyongyi Szabo Hepatitis C virus infection affects 170 million people worldwide, and the majority of individuals exposed to HCV develop chronic hepatitis leading to progressive liver damage, cirrhosis, and hepatocellular cancer. The natural history of HCV infection is influenced by genetic and environmental factors of which chronic alcohol use is an independent risk factor for cirrhosis in HCV-infected individuals. Both the hepatitis C virus and alcohol damage the liver and result in immune alterations contributing to both decreased viral clearance and liver injury. This review will capture the major components of the interactions between alcohol and HCV infection to provide better understanding for the molecular basis of the dangerous combination of alcohol use and HCV infection. Common targets of HCV and alcohol involve innate immune recognition and dendritic cells, the critical cell type in antigen presentation and antiviral immunity. In addition, both alcohol and HCV affect intracellular processes critical for hepatocyte and immune cell functions including mitochondrial and proteasomal activation. Finally, both chronic alcohol use and hepatitis C virus infection increase the risk of hepatocellular cancer. The common molecular mechanisms underlying the pathological interactions between alcohol and HCV include the modulation of cytokine production, lipopolysaccharide (LPS)-TLR4 signaling, and reactive oxygen species (ROS) production. LPS-induced chronic inflammation is not only a major cause of progressive liver injury and fibrosis, but it can also contribute to modification of the tissue environment and stem cells to promote hepatocellular cancer development. Alteration of these processes by alcohol and HCV produces an environment of impaired antiviral immune response, greater hepatocellular injury, and activation of cell proliferation and dedifferentiation. [source] Differential modulation of innate immune cell functions by the Burkholderia cepacia complex: Burkholderia cenocepacia but not Burkholderia multivorans disrupts maturation and induces necrosis in human dendritic cellsCELLULAR MICROBIOLOGY, Issue 10 2008Kelly L. MacDonald Summary Burkholderia cepacia complex (BCC) bacteria cause pulmonary infections that can evolve into fatal overwhelming septicemia in chronic granulomatous disease or cystic fibrosis patients. Burkholderia cenocepacia and Burkholderia multivorans are responsible for the majority of BCC infections in cystic fibrosis patients, but B. cenocepacia is generally associated with a poorer prognosis than B. multivorans. The present study investigated whether these pathogens could modulate the normal functions of primary human monocyte-derived dendritic cells (DCs), important phagocytic cells that act as critical orchestrators of the immune response. Effects of the bacteria on maturation of DCs were determined using flow cytometry. DCs co-incubated for 24 h with B. cenocepacia, but not B. multivorans, had reduced expression of costimulatory molecules when compared with standard BCC lipopolysaccharide-matured DCs. B. cenocepacia, but not B. multivorans, also induced necrosis in DCs after 24 h, as determined by annexin V and propidium iodide staining. DC necrosis only occurred after phagocytosis of live B. cenocepacia; DCs exposed to heat-killed bacteria, bacterial supernatant or those pre-treated with cytochalasin D then exposed to live bacteria remained viable. The ability of B. cenocepacia to interfere with normal DC maturation and induce necrosis may contribute to its pathogenicity in susceptible hosts. [source] | |||||||||||||