Search results for "CD8"

Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy

2001

DNA-based immunization represents an attractive alternative approach to the current treatment of allergic diseases by specific immunotherapy with allergen extracts. In this study, we used a replication-deficient adenovirus vector (AdCMV), to examine the in vivo efficacy of preventive and therapeutic genetic immunization in a mouse model of type I allergy. Primary immunization with a recombinant adenovirus expressing the model antigen beta-galactosidase (AdCMV-(beta)gal) induced a Th1 immune response (predominance of IgG2a antibodies, high frequency of IFN-gamma producing T cells) and large numbers of cytotoxic T lymphocytes. Prophylactic vaccination with AdCMV-(beta)gal abolished the produc…

Interferon-α Abrogates Tolerance Induction by Human Tolerogenic Dendritic Cells

2011

Background Administration of interferon-α (IFN-α) represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-α on tolerance induction by human tolerogenic dendritic cells (DC) was analyzed. We focussed on tolerogenic IL-10-modulated DC (IL-10 DC) that are known to induce anergic regulatory T cells (iTregs). Methodology/Principal Findings IFN-α promoted an enhanced maturation of IL-10 DC as demonstrated by upregulation of the differentiation marker CD83 as well as costimulatory molecules. IFN-α treatment resulted in an…

2004

Autoimmune inflammation, such as in rheumatoid arthritis, is characterized by activated Th1 cells without sufficient Th2 differentiation that might downmodulate the chronic immune response. Delineation of the mechanisms that control T-cell differentiation is therefore of major importance for the understanding of the pathogenesis of autoimmune diseases. The transcription factor GATA-3 has been implicated in regulating Th2 cell differentiation in murine T cells in vitro, but its role in vivo and, in particular, in human T-cell differentiation is currently unknown. To dissect the role of GATA-3 in human T-cell differentiation and T-cell-mediated effector functions, we used the unique opportuni…

Dendritic cells and the handling of antigen

2003

Dendritic cells (DC) are a sparsely distributed, migratory group of bone marrow-derived leucocytes that are specialized for the uptake, transport, processing and presentation of antigens to T cells [1,2]. At an immature stage of development DC are considered as the first-line sentinels in immune surveillance of peripheral tissues, including epithelia of the skin and mucosal surfaces, where they sample continuously the antigenic local microenvironment by uptake of self- and exogenous antigen via macropinocytosis/endocytosis [3,4]. The efficiency of DC to initiate an immune response against infectious disease is due to their constant trafficking between peripheral tissues and draining lymph n…

PD-1-induced T cell exhaustion is controlled by a Drp1-dependent mechanism

2020

AbstractPD-1 signalling downregulates the T cell response, promoting an exhausted state in tumor-infiltrating T cells, through mostly unveiled molecular mechanisms. Drp1-dependent mitochondrial fission plays a crucial role to sustain T cell motility, proliferation, survival and glycolytic engagement and, interestingly, such processes are exactly those inhibited by PD-1 in tumor-infiltrating T cells. Here we show that the signature of PD-1pos CD8+ T cells infiltrating MC38-derived murine tumor mass is having downregulated Drp1 activity and more fused mitochondria, compared to PD-1neg counterparts. Also, PD-1pos lymphocytic elements infiltrating human colon cancer rarely express active Drp1. …

Stalemating a clever opportunist: lessons from murine cytomegalovirus.

2003

Abstract Cytomegaloviruses and their specific hosts have come to an arrangement that avoids disease but allows the viruses to persist in the individual host and to spread in the host species. Recent work has uncovered some of the molecular details of this evolutionary “contract for mutual survival.” Cytomegaloviruses encode proteins, referred to as “immunoevasins,” which are specifically committed to subvert the immune defense of the host for evading virus elimination. In reply, the hosts have evolved countermeasures to overcome the viral immunoevasins and present antigenic peptides to an extent that is sufficient for confining virus replication to below a harmful level. Accordingly, cytome…

Macrophages Escape Inhibition of Major Histocompatibility Complex Class I-Dependent Antigen Presentation by Cytomegalovirus

2000

ABSTRACTThe mouse cytomegalovirus (MCMV)m152- andm06-encoded glycoproteins gp40 and gp48, respectively, independently downregulate major histocompatibility complex (MHC) class I surface expression during the course of productive MCMV infection in fibroblasts. As a result, presentation of an immediate-early protein pp89-derived nonapeptide toH-2Ld-restricted CD8+cytotoxic T cells is completely prevented in fibroblasts. Here we demonstrate that MCMV-infected primary bone marrow macrophages and the macrophage cell line J774 constitutively present pp89 peptides during permissive MCMV infection to cytotoxic T lymphocytes (CTL). In contrast to fibroblasts, expression of them152andm06genes in macr…

Prophylactic and therapeutic intervention in IgE responses by biolistic DNA vaccination primarily targeting dendritic cells.

2005

Background Allergen gene transfer represents an alternative approach to specific immunotherapy with allergen extracts. Gene gun–mediated DNA immunization with plasmid vectors expressing a transgene under control of the promoter of the fascin gene (pFascin) allows for antigen production predominantly by dendritic cells and resulted in the generation of CD8 + cytotoxic T lymphocytes as well as in the development of a type 1 immune response. Objective We compared the in vivo efficiency of biolistic transfection with pFascin and plasmids containing the cytomegalovirus promoter (pCMV) in a mouse model of type I allergy. Methods BALB/c mice were sensitized with the model allergen β-galactosidase …

Enrichment of Immediate-Early 1 (m123/pp89) Peptide-Specific CD8 T Cells in a Pulmonary CD62LloMemory-Effector Cell Pool during Latent Murine Cytomeg…

2000

ABSTRACTInterstitial cytomegalovirus (CMV) pneumonia is a clinically relevant complication in recipients of bone marrow transplantation (BMT). Recent data for a model of experimental syngeneic BMT and concomitant infection of BALB/c mice with murine CMV (mCMV) have documented the persistence of tissue-resident CD8 T cells after clearance of productive infection of the lungs (J. Podlech, R. Holtappels, M.-F. Pahl-Seibert, H.-P. Steffens, and M. J. Reddehase, J. Virol. 74:7496–7507, 2000). It was proposed that these cells represent antiviral “standby” memory cells whose functional role might be to help prevent reactivation of latent virus. The pool of pulmonary CD8 T cells was composed of two…

Cyclic adenosine monophosphate and IL-10 coordinately contribute to nTreg cell-mediated suppression of dendritic cell activation

2010

In humans and mice naturally occurring regulatory T cells (nTregs) are crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Here we show that co-culture of murine dendritic cells (DC) and nTregs results in an immediate increase of cAMP in DC, responsible for a rapid down-regulation of co-stimulatory molecules (CD80, CD86). In addition, the inhibitory surface molecule B7-H3 on DC is up-regulated. Subsequently, nTreg-derived IL-10 inhibits the cytokine production (IL-6, IL-12) of suppressed DC therewith preserving their silent phenotype. Hence, our data indicate that nTreg…