Search results for "G cell"

Structure-Activity Relationships and X-ray Structures Describing the Selectivity of Aminopyrazole Inhibitors for c-Jun N-terminal Kinase 3 (JNK3) ove…

2009

c-Jun N-terminal kinase 3alpha1 (JNK3alpha1) is a mitogen-activated protein kinase family member expressed primarily in the brain that phosphorylates protein transcription factors, including c-Jun and activating transcription factor-2 (ATF-2) upon activation by a variety of stress-based stimuli. In this study, we set out to design JNK3-selective inhibitors that had >1000-fold selectivity over p38, another closely related mitogen-activated protein kinase family member. To do this we employed traditional medicinal chemistry principles coupled with structure-based drug design. Inhibitors from the aminopyrazole class, such as SR-3576, were found to be very potent JNK3 inhibitors (IC(50) = 7 nm)…

The NFκB-inducing kinase is essential for the developmental programming of skin-resident and IL-17-producing γδ T cells

2015

γδ T cells contribute to first line immune defense, particularly through their ability for rapid production of proinflammatory cytokines. The cytokine profile of γδ T cells is hard-wired already during thymic development. Yet, the molecular pathways underlying this phenomenon are incompletely understood. Here we show that signaling via the NFκB-inducing kinase (NIK) is essential for the formation of a fully functional γδ T cell compartment. In the absence of NIK, development of Vγ5+ dendritic epidermal T cells (DETCs) was halted in the embryonic thymus, and impaired NIK function caused a selective loss of IL-17 expression by γδ T cells. Using a novel conditional mutant of NIK, we could show…

2014

The maturation status of dendritic cells determines whether interacting T cells are activated or if they become tolerant. Previously we could induce T cell tolerance by applying a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor (HMGCRI) atorvastatin, which also modulates MHC class II expression and has therapeutic potential in autoimmune disease. Here, we aimed at elucidating the impact of this therapeutic strategy on T cell differentiation as a consequence of alterations in dendritic cell function. We investigated the effect of HMGCRI during differentiation of peripheral human monocytes and murine bone marrow precursors to immature DC in vitro and assessed their phenotype. To …

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 as a …

Comment on "Human Neuroblasts Migrate to the Olfactory Bulb via a Lateral Ventricular Extension"

2007

Curtis et al . (Research Articles, 2 March 2007, p. 1243) claimed discovery of a human neuronal migratory stream to the olfactory bulb along a putative lateral ventricular extension. However, high levels of proliferation reported with proliferating cell nuclear antigen were not confirmed using different markers, neuronal chain migration was not demonstrated, and no serial reconstruction shows a true ventricular extension.

Adoptive CD8 T Cell Control of Pathogens Cannot Be Improved by Combining Protective Epitope Specificities

2008

Adoptive transfer of CD8 T cells has the potential to cure infectious or malignant diseases that are refractory to conventional chemotherapy. A practically important but still unanswered question is whether mixtures of protective CD8 T cells with different epitope specificities mediate more efficient effector cell functions than do the monospecific individual CD8 T cell populations. In this study, we have addressed this issue for models of viral and bacterial infection. CD8 T cell-mediated cytotoxicity in vitro and protection in vivo were assessed to test whether CD8 T cell lines cooperate in target cell lysis and control of infection, respectively. Our data clearly show that mixtures of cy…

Virally Infected Mouse Liver Endothelial Cells Trigger CD8+ T-Cell Immunity

2009

Background & Aims Dendritic cell activation through ligation of pattern recognition receptors leading to full functional maturation causes induction of CD8 + T-cell immunity through increased delivery of costimulatory signals instead of tolerance. Here we investigate whether organ-resident antigen-presenting cells, such as liver sinusoidal endothelial cells (LSECs), also switch from tolerogenic to immunogenic CD8 + T-cell activation upon such stimulation. Methods Murine LSECs were isolated by immunomagnetic separation and analyzed for functional maturation upon triggering pattern recognition receptors or viral infection employing gene expression analysis and T cell coculture assays. In vivo…

Circulating cell-free DNA (cfDNA) and extracellular vesicles (EVs) as prognostic and predictive biomarkers in patients with advanced Non-Small Cell L…

2022

Rate capability of a cryogenic stopping cell for uranium projectile fragments produced at 1000 MeV/u

2016

At the Low-Energy Branch (LEB) of the Super-FRS at FAIR, projectile and fission fragments will be produced at relativistic energies, separated in-flight, energy-bunched, slowed down and thermalized in a cryogenic stopping cell (CSC) filled with ultra-pure He gas. The fragments are extracted from the stopping cell using a combination of DC and RF electric fields and gas flow. A prototype CSC for the LEB has been developed and successfully commissioned at the FRS Ion Catcher at GSI. Ionization of He buffer gas atoms during the stopping of energetic ions creates a region of high space charge in the stopping cell. The space charge decreases the extraction efficiency of stopping cells since the …

The FRS Ion Catcher

2013

At the FRS Ion Catcher at GSI, projectile and fission fragments are produced at relativistic energies, separated in-flight, range-focused, slowed down and thermalized in a cryogenic stopping cell. A multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS) is used to perform direct mass measurements and to provide an isobarically clean beam for further experiments, such as mass-selected decay spectroscopy. A versatile RF quadrupole transport and diagnostics unit guides the ions from the stopping cell to the MR-TOF-MS, provides differential pumping, ion identification and includes reference ion sources. The FRS Ion Catcher serves as a test facility for the Low-Energy Branch of the Sup…