Search results for "differentiation"

Subviral Dense Bodies of Human Cytomegalovirus Stimulate Maturation and Activation of Monocyte-Derived Immature Dendritic Cells

2013

ABSTRACT Dendritic cells play a central role in the immune control of human cytomegalovirus (HCMV) infection. This work aimed at investigating the impact of noninfectious, subviral dense bodies of HCMV on the maturation and activation of dendritic cells (DC). Treatment of immature DC with dense bodies led to the maturation of these cells and significantly increased their capacity for cytokine release and antigen presentation. Dense body-activated DC may thereby contribute to the development of antiviral immunity.

Identification of biological markers of liver X receptor (LXR) activation at the cell surface of human monocytes.

2012

Background Liver X receptor (LXR) α and LXR β (NR1H3 and NR1H2) are oxysterol-activated nuclear receptors involved in the control of major metabolic pathways such as cholesterol homeostasis, lipogenesis, inflammation and innate immunity. Synthetic LXR agonists are currently under development and could find applications in various fields such as cardiovascular diseases, cancer, diabetes and neurodegenerative diseases. The clinical development of LXR agonists requires the identification of biological markers for pharmacodynamic studies. In this context, monocytes represent an attractive target to monitor LXR activation. They are easily accessible cells present in peripheral blood; they expres…

Isomer effects in fragmentation of Polycyclic Aromatic Hydrocarbons

2015

We have observed significant differences in the fragmentation patterns of isomeric Polycyclic Aromatic Hydrocarbon (PAH) cations following collisions with helium atoms at center-of-mass energies around 100 eV. This is in contrast to the situation at other collision energies or in photo-absorption experiments where isomeric effects are very weak and where the lowest-energy dissociation channels (H- and C2H2-loss) domihate in statistical fragmentation processes. In the 100 eV range, non-statistical fragmentation also competes and is uniquely linked to losses of single carbon atoms (CHx-losses). We find that such CHx-losses are correlated with the ionic ground state energy within a given group…

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…

Revisiting Current Concepts on the Tolerogenicity of Steady-State Dendritic Cell Subsets and Their Maturation Stages

2021

Abstract The original concept stated that immature dendritic cells (DC) act tolerogenically whereas mature DC behave strictly immunogenically. Meanwhile, it is also accepted that phenotypically mature stages of all conventional DC subsets can promote tolerance as steady-state migratory DC by transporting self-antigens to lymph nodes to exert unique functions on regulatory T cells. We propose that in vivo 1) there is little evidence for a tolerogenic function of immature DC during steady state such as CD4 T cell anergy induction, 2) all tolerance as steady-state migratory DC undergo common as well as subset-specific molecular changes, and 3) these changes differ by quantitative and qualitati…

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

2011

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have ena…

Suppressor activity of anergic T cells induced by IL-10-treated human dendritic cells: association with IL-2- and CTLA-4-dependent G1 arrest of the c…

2003

We have previously shown that human IL-10-treated dendritic cells (DC) induce an antigen-specific anergy in CD4+ T lymphocytes. These anergic T cells are characterized by an inhibited proliferation, a reduced production of IL-2, and additionally display antigen-specific suppressor activity. In this study we investigated the mechanisms underlying the anergic state and regulatory function of these T cells. We did not observe enhanced rates of programmed cell death of anergic CD4+ suppressor T cells compared to T cells stimulated with mature DC. Cell cycle analysis by DNA staining and Western blot experiments revealed an arrest of anergic CD4+ T suppressor cells in the G1 phase. High levels of…

Tuning tumor-specific T-cell activation: a matter of costimulation?

2002

Abstract The stimulation of a specific antitumor immune response, involving the recruitment of T cells and induction of T-cell effector functions, is an attractive possibility for cancer immunotherapy. In the past few years, advances in our understanding of the mechanisms of T-cell activation and costimulation have provided the basis for strategies to enhance antitumor immunity and break tolerance. These strategies include the equipment of tumor cells with costimulatory molecules such as B7, blockade of inhibitory signals on T cells (e.g. through cytotoxic T-lymphocyte antigen 4) and grafting of T cells with antigen-triggered, recombinant costimulatory receptors. Combining antigen-triggered…

Identification and Functional Characterization of Human Cd4+Cd25+ T Cells with Regulatory Properties Isolated from Peripheral Blood

2001

A subpopulation of peripheral human CD4(+)CD25(+) T cells that expresses CD45RO, histocompatibility leukocyte antigen DR, and intracellular cytotoxic T lymphocyte-associated antigen (CTLA) 4 does not expand after stimulation and markedly suppresses the expansion of conventional T cells in a contact-dependent manner. After activation, CD4(+)CD25(+) T cells express CTLA-4 on the surface detectable for several weeks. These cells show a G1/G0 cell cycle arrest and no production of interleukin (IL)-2, IL-4, or interferon (IFN)-gamma on either protein or mRNA levels. The anergic state of CD4(+)CD25(+) T cells is not reversible by the addition of anti-CD28, anti-CTLA-4, anti-transforming growth fa…