Search results for "CD8"
showing 10 items of 682 documents
Rapid identification and sorting of viable virus-reactive CD4+ and CD8+ T cells based on antigen-triggered CD137 expression
2008
Abstract Current methods for the detection and isolation of antigen-specific CD4 + and CD8 + T cells require the availability of peptide/MHC multimers or are restricted to cells that produce cytokines after antigen contact. Here we show that de novo cell surface expression of the TNF-receptor family member CD137 (4-1BB) identifies recently activated, but not resting, human CD4 + and CD8 + memory T cells. Maximum CD137 expression level is uniformly observed in both T-cell subsets at 24h after stimulation with antigen. In experiments with CMV and EBV-reactive T cells, we confirmed the specificity of CD137 expression by co-staining with peptide/HLA tetramers. Substantial proportions of CD137 +…
Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines.
2006
AbstractIn HLA-incompatible hematopoietic stem cell transplantation, alloreactive donor T cells recognizing recipient mismatch HLA cause severe graft-versus-host disease (GVHD). Strategies allowing the selective depletion of alloreactive T cells as well as the enhancement of graft-versus-malignancy immunity would be beneficial. We generated donor CD8 T-cell lines in vitro using allogeneic recipient cells mismatched at a single HLA class I allele or haplotype as stimulators. Recipient cells were obtained from acute myeloid leukemias, renal-cell carcinomas, and CD40L-induced B lymphoblasts. Resulting alloreactive T cells were activated by incubating day 21 T-cell cultures with HLA-mismatch tr…
Human dendritic cells transfected with allergen-DNA stimulate specific immunoglobulin G4 but not specific immunoglobulin E production of autologous B…
2007
Atopic/allergic diseases are characterized by T helper 2 (Th2)-dominated immune responses resulting in immunoglobulin E (IgE) production. DNA-based immunotherapies have been shown to shift the immune response towards Th1 in animal models. In further studies we showed that human dendritic cells (DC) transfected with allergen-DNA are able to stimulate autologous CD4(+) T cells from atopic individuals to produce Th1 instead of Th2 cytokines and to activate interferon-gamma (IFN-gamma)-producing CD8(+) T cells. The aim of this study was to analyse whether DC transfected with allergen-DNA are also able to influence immunoglobulin production of B cells from atopic donors. For this purpose, human …
Inhibition of human allergic T-cell responses by IL-10–treated dendritic cells: Differences from hydrocortisone-treated dendritic cells
2001
Abstract Background: Dendritic cells (DCs) are able to induce human allergic T H 1 responses as well as T H 2 responses. Objective: In this study, we examined the effect of antiinflammatory agents such as IL-10 and hydrocortisone (HC) on the accessory function of DCs and the resulting T-cell response, especially that of T H 2 cells. Methods: Naive and memory CD4 + T cells from atopic donors were stimulated with autologous allergen-pulsed DCs generated from CD14 + monocytes by culture with GM-CSF/IL-4 and fully matured with IL-1β, TNF-α, and PGE 2 in the presence or absence of IL-10 or HC. Results: IL-10–treated DCs and, to a lesser extent, HC-treated DCs showed a decreased expression of MHC…
Modification of the human allergic immune response by allergen-DNA-transfected dendritic cells in vitro.
2004
Abstract Background Atopic-allergic diseases are characterized by T H 2-dominated immune responses, resulting in IgE production. DNA-based immunotherapies have been shown to shift the immune response toward a T H 1-type response in animal models. Objective The aim of the study was to analyze whether dendritic cells (DCs) transfected with allergen-DNA conjugates are able to stimulate human autologous CD4 + T cells, CD8 + T cells, or both from atopic individuals to produce T H 1 cytokines instead of T H 2 cytokines. Methods For this purpose, human mature DCs from atopic donors were transfected with an adenovirus encoding the allergen Phl p 1. Autologous CD4 + and CD8 + T cells were stimulated…
MHC class II tetramer guided detection of Mycobacterium tuberculosis-specific CD4+ T cells in peripheral blood from patients with pulmonary tuberculo…
2007
Novel diagnostic tools are needed to diagnose latent infection and to provide biologically meaningful surrogate markers to define cellular immune responses against Mycobacterium tuberculosis (MTB). Interferon gamma-based assays have recently been developed in addition to the more than 100-year-old tuberculin skin test (TST) for the immune diagnosis of MTB in blood. The advent of soluble MHC/peptide tetramer molecules allows to objectively enumerate antigen-specific T cells. We identified novel MHC class II-restricted MTB epitopes and used HLA-DR4 tetrameric complexes to visualize ex vivo CD4(+) T cells directed against the antigens Ag85B and the 19-kDa lipoprotein, shared between MTB and ot…
CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity.
2002
Interleukin-10 (IL-10)–treated dendritic cells (DCs) induce an alloantigen- or peptide-specific anergy in various CD4+ and CD8+ T-cell populations. In the present study, we analyzed whether these anergic T cells are able to regulate antigen-specific immunity. Coculture experiments revealed that alloantigen-specific anergic CD4+ and CD8+ T cells suppressed proliferation of syngeneic T cells in a dose-dependent manner. The same effect was observed when the hemagglutinin-specific CD4+T-cell clone HA1.7 or tyrosinase-specific CD8+ T cells were cocultured with anergic T cells of the same specificity. Anergic T cells did not induce an antigen-independent bystander inhibition. Suppression was depe…
Inhibitors of β-catenin affect the immuno-phenotype and functions of dendritic cells in an inhibitor-specific manner
2015
Many tumors are characterized by mutation-induced constitutive activation of β-catenin which promotes tumor growth and survival. Consequently, the development of specific β-catenin inhibitors for tumor therapy has come into the focus of drug development. β-Catenin was also shown to contribute to the tolerance-promoting function of unstimulated dendritic cells (DCs). In response to activation, DCs acquire potent T cell stimulatory capacity and induce profound tumor antigen-specific immune responses. Here we asked for effects of pre-clinically established β-catenin inhibitors (CCT-031374, iCRT-5, PNU-75654) on mouse bone marrow-derived (BM)DCs. All three inhibitors moderately increased surfac…
Glycoprotein 96-activated dendritic cells induce a CD8-biased T cell response.
2005
Heat shock proteins (Hsps) are able to induce protective immune responses against pathogens and tumors after injection into immunocompetent hosts. The activation of components of the adaptive immune system, including cytotoxic T lymphocytes specific for pathogen- or tumor-derived peptides, is crucial for the establishment of immuno- protection. Hsps acquire these peptides during intracellular protein degradation and when released during necrotic cell death, facilitate their uptake and Minor Histocompatibility Complex (MHC)-restricted representation by professional antigen-presenting cells (APCs). In addition, the interaction of Hsps with APCs, including the Endoplasmatic Reticulum (ER)-resi…
A trifunctional dextran-based nanovaccine targets and activates murine dendritic cells, and induces potent cellular and humoral immune responses in v…
2013
Dendritic cells (DCs) constitute an attractive target for specific delivery of nanovaccines for immunotherapeutic applications. Here we tested nano-sized dextran (DEX) particles to serve as a DC-addressing nanocarrier platform. Non-functionalized DEX particles had no immunomodulatory effect on bone marrow (BM)-derived murine DCs in vitro. However, when adsorbed with ovalbumine (OVA), DEX particles were efficiently engulfed by BM-DCs in a mannose receptor-dependent manner. A DEX-based nanovaccine containing OVA and lipopolysaccharide (LPS) as a DC stimulus induced strong OVA peptide-specific CD4(+) and CD8(+) T cell proliferation both in vitro and upon systemic application in mice, as well a…