Search results for "T cell"
showing 10 items of 2228 documents
The role of CD8+ T cells and their local interaction with CD4+ T cells in myelin oligodendrocyte glycoprotein35-55-induced experimental autoimmune en…
2013
Abstract T cells have an essential role in the induction of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Although for CD4+ T cells it is well established that they contribute to the disease, less is known about the role of CD8+ T cells. Our aim was to determine the individual contribution of CD4+ and CD8+ T cells in myelin oligodendrocyte glycoprotein (MOG)35–55–induced EAE. We investigated MOG35–55–activated CD8+ T cells to clarify their potential to induce or attenuate EAE. We monitored the behavior of CD8+ T cells and their interaction with CD4+ T cells directly at the site of inflammation in the CNS using intravital imaging of the brainstem of…
Cross-recognition of a myelin peptide by CD8+ T cells in the CNS is not sufficient to promote neuronal damage.
2015
Multiple sclerosis (MS) is an inflammatory disease of the CNS thought to be driven by CNS-specific T lymphocytes. Although CD8+T cells are frequently found in multiple sclerosis lesions, their distinct role remains controversial because direct signs of cytotoxicity have not been confirmedin vivo. In the present work, we determined that murine ovalbumin-transgenic (OT-1) CD8+T cells recognize the myelin peptide myelin oligodendrocyte glycoprotein 40–54 (MOG40–54) bothin vitroandin vivo. The aim of this study was to investigate whether such cross-recognizing CD8+T cells are capable of inducing CNS damagein vivo. Using intravital two-photon microscopy in the mouse model of multiple sclerosis, …
Modulation of dendritic cell properties by laquinimod as a mechanism for modulating multiple sclerosis.
2013
Laquinimod is an orally administered compound that is under investigation in relapsing-remitting multiple sclerosis. To understand the mechanism by which laquinimod exerts its clinical effects, we have performed human and murine studies assessing its immunomodulatory properties. In experimental autoimmune encephalomyelitis, the therapeutic administration of laquinimod beginning during the recovery of SJL mice, prevented further relapses as expected and strongly reduced infiltration of CD4+ and CD8+ T cells in the central nervous system. We hypothesized that this beneficial effect was mediated by dendritic cells, since we and others found a modulation of different dendritic cell subsets unde…
Treatment of T Cell-Dependent Experimental Colitis in SCID Mice by Local Administration of an Adenovirus Expressing IL-18 Antisense mRNA
2001
Abstract Recent studies have shown that IL-18, a pleiotropic cytokine that augments IFN-γ production, is produced by intestinal epithelial cells and lamina propria cells from patients with Crohn’s disease. In this study, we show that IL-18 is strongly expressed by intestinal epithelial cells in a murine model of Crohn’s disease induced by transfer of CD62L+CD4+ T cells into SCID mice. To specifically down-regulate IL-18 expression in this model, we constructed an E1/E3-deleted adenovirus expressing IL-18 antisense mRNA, denoted Ad-asIL-18, and demonstrated the capacity of such a vector to down-regulate IL-18 expression in colon-derived DLD-1 cells and RAW264.7 macrophages. Local administrat…
Reconstitution of CD8 T cells is essential for the prevention of multiple-organ cytomegalovirus histopathology after bone marrow transplantation.
1998
Cytomegalovirus (CMV) infection in the period of temporary immunodeficiency after haematoablative treatment and bone marrow transplantation (BMT) is associated with a risk of graft failure and multiple-organ CMV disease. The efficacy of immune system reconstitution is decisive for the prevention of CMV pathogenesis after BMT. Previous data in murine model systems have documented a redundancy in the immune effector mechanisms controlling CMV. CD8 T cells proved to be relevant but not irreplaceable as antiviral effectors. Specifically, in a state of long-term in vivo depletion of the CD8 T-cell subset, CD4 T cells were educed to become deputy effectors controlling CMV by a mechanism involving…
In vitro model for the activation of CD4 and CD8 T cell receptors.
2008
Previously, most models that sought to explain the misregulation of immune cell function assumed molecular similarities between the disease-causing pathogens and the host's proteins. In recent time several different models have been proposed and in this study, these concepts are compared to a new hypothesis proposing another explanation for this immune dysregulation: the possibility that the mislocalization of proteins may be responsible for autoimmune activity. Based on this hypothesis, proteins are recognized as self or non-self depending on where they appear in sufficiently high concentrations. To examine this new idea, the intracellular human proteins beta-actin, GAPDH, and hemoglobin a…
CD8+ cytotoxic T lymphocytes isolated from allogeneic healthy donors recognize HLA class Ia/Ib–associated renal carcinoma antigens with ubiquitous or…
2004
AbstractAllogeneic hematopoietic stem cell transplantation can induce considerable tumor remissions in metastatic renal-cell carcinoma (RCC) patients. The precise effector mechanisms mediating these graft-versus-tumor reactions are unknown. We studied RCC-directed CD8+ T-cell responses in blood lymphocytes of healthy individuals matched with established RCC cell lines for HLA-class I. In 21 of 22 allogeneic mixed lymphocyte/tumor-cell cultures (MLTCs), RCC-reactive cytotoxic T-lymphocytes (CTLs) were readily obtained. From MLTCs, 121 CD8+ CTL clones with memory phenotype were isolated. Their anti–RCC reactivity was restricted by multiple classical HLA-Ia molecules, in particular by HLA-A2, …
Uptake and presentation of exogenous antigen and presentation of endogenously produced antigen by skin dendritic cells represent equivalent pathways …
2008
Gene gun-mediated biolistic DNA vaccination with beta-galactosidase (betaGal)-encoding plasmid vectors efficiently modulated antigen-induced immune responses in an animal model of type I allergy, including the inhibition of immunoglobulin E (IgE) production. Here we show that CD4(+) as well as CD8(+) T cells from mice biolistically transfected with a plasmid encoding betaGal under the control of the fascin promoter (pFascin-betaGal) are capable of inhibiting betaGal-specific IgE production after adoptive transfer into naïve recipients. Moreover, suppression of IgE production was dependent on interferon (IFN)-gamma. To analyse the modalities of activation of CD4(+) and CD8(+) T cells regardi…
Clonal analysis of human T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis
1988
Human T lymphocytes infiltrating the liver in chronic active hepatitis B (CAH-B) and primary biliary cirrhosis were isolated from liver biopsy cores, cloned by limiting dilution technique and expanded in vitro. Phenotypic and functional analysis demonstrates that this tissue infiltrate represents a heterogeneous cell population. However, when compared to peripheral blood lymphocytes of the same patients, a marked enrichment for T8+ cytotoxic T cells was found to exist at a local site in both types of chronic liver disease. These data provide support for the notion that liver cell injury in CAH-B and PBC may be mediated by a common immunologic mechanism likely executed by cells of the T line…
Perforin deficiency attenuates inflammation and tumor growth in colitis-associated cancer
2010
Background: Patients with inflammatory bowel disease (IBD) have a markedly increased risk to develop colon cancer, but there are only limited data about the host antitumor response in such colitis-associated cancer. In the present study we aimed at assessing the role of perforin-dependent effector mechanisms in the immune response in a murine model of colitis-associated colon cancer. Methods: Wildtype and perforin-deficient mice were analyzed in a mouse model of colitis-associated colon cancer using azoxymethane (AOM) and dextran sodium sulfate (DSS). Results: Tumors of wildtype mice showed infiltration of CD4+, CD8+ T cells, natural killer (NK) cells, high numbers of apoptotic cells, and e…