Search results for "T cell"

The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells

2015

The modification of proteins by ubiquitin has a major role in cells of the immune system and is counteracted by various deubiquitinating enzymes (DUBs) with poorly defined functions. Here we identified the ubiquitin-specific protease USP8 as a regulatory component of the T cell antigen receptor (TCR) signalosome that interacted with the adaptor Gads and the regulatory molecule 14-3-3β. Caspase-dependent processing of USP8 occurred after stimulation of the TCR. T cell-specific deletion of USP8 in mice revealed that USP8 was essential for thymocyte maturation and upregulation of the gene encoding the cytokine receptor IL-7Rα mediated by the transcription factor Foxo1. Mice with T cell-specifi…

Increased regulatory T-cell frequencies in patients with advanced melanoma correlate with a generally impaired T-cell responsiveness and are restored…

2009

Naturally occurring CD4(+) CD25(+) regulatory T-cell (Treg) activity is assumed to facilitate tumor development and progression. To elucidate the possible role of Tregs in the course of melanoma progression, we analysed the frequency of Tregs in the peripheral blood of patients at melanoma stages I-IV and in patients at melanoma stage IV that underwent dendritic cell (DC)-based immunotherapy. Using CD25, Foxp3, CD127 and HLA-DR as Treg associated markers, we observed increased Treg frequencies in patients at the late melanoma stage (stage IV) when compared to healthy donors. Accumulation of Tregs in patients with progressed melanoma correlated with a general reduction of T-cell responsivene…

Effects of Regulatory T Cell–Dendritic Cell Interactions on Adaptive Immune Responses

2014

The limited efficacy of chemo- or radiotherapy against neoplasias necessitates the development of complementary therapeutic strategies. Tumor immunotherapy represents a promising approach as it harnesses the potential of the host immune system to recognize and eradicate transformed cells. So far, T cell-based immunotherapy still suffers from a striking discrepancy between the induction of tumor-specific immune responses in experimental settings and therapeutic immunity in clinically relevant conditions. However, therapeutic approaches targeting immune regulatory mechanisms have lately shown encouraging results and have initiated long-lasting tumor control in patients. Therefore, a deeper un…

Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation

2009

Abstract The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellular components were put in contact. Reversal of Treg suppression required T cell–derived interleukin-6 (IL-6) and the OX40/OX40L axis. In the presence of activated MCs, concomitant abundance of IL-6 and paucity of Th1/Th2 cytokines skewed Tregs and effector T cells into IL-17–producing T cel…

2013

Dendritic cells (DC) are sentinels of immunity, essential for homeostasis of T cell-dependent immune responses. Both functions of DC, initiation of antigen-specific T cell immunity and maintenance of tissue-specific tolerance originate from distinct stages of differentiation, immunogenic versus tolerogenic. Dependent on local micro milieu and inflammatory stimuli, tissue resident immature DC with functional plasticity differentiate into tolerogenic or immunogenic DC with stable phenotypes. They efficiently link innate and adaptive immunity and are ideally positioned to modify T cell-mediated immune responses. Since the T cell stimulatory properties of DC are significantly influenced by thei…

Polyethyleneimine-based immunopolyplex for targeted gene transfer in human lymphoma celllines

2002

Background Specific and efficient delivery of genes into targeted cells is a priority objective in non-viral gene therapy. Polyethyleneimine-based polyplexes have been reported to be good non-viral transfection reagents. However, polyplex-mediated DNA delivery occurs through a non-specific mechanism. This article reports the construction of an immunopolyplex, a targeted non-viral vector based on a polyplex backbone, and its application in gene transfer over human lymphoma cell lines. Methods Targeting elements (biotin-labeled antibodies), which should recognize a specific element of the target cell membrane and promote nucleic acid entry into the cell, were attached to the polyplex backbone…

Establishment of an HIV cell-cell fusion assay by using two genetically modified HeLa cell lines and reporter gene.

2003

Infection of human cells with the human immunodeficiency virus type I (HIV-1) can be mimicked by a fusion process between cells expressing the HIV envelope protein (Env) and cells expressing both human CD4 together with the appropriate human chemokine receptors. In this study, a T-tropic HIV cell-cell fusion assay was established that utilized CD4, human CXCR4 and HIV NL4-3 gp160 as fusion components and a T7 polymerase-activated luciferase as a reporter system. The HeLa T4 cells used, expressed CD4 and CXCR4, and the applied HeLa KS386 cells expressed HIV NL4-3 gp160. By combining HeLa T4 cells with HeLa KS386 cells, an approximately about 100- to 300-fold increase in luciferase activity c…

Activation of Mast Cells by Streptolysin O and Lipopolysaccharide

2005

This chapter provides protocols to measure the reversible permeabilization of mast cells by streptolysin O (SLO) and to follow SLO-induced activation of mast cells by monitoring degranulation, activation of mitogen-activated protein kinases, and production of tumor necrosis factor-alpha. A method that uses SLO to deliver molecules into the cytosol of living cells also is described. Furthermore, we outline a procedure to measure the activation of nuclear factor-kappaB by lipopolysaccharide and ionomycin using transfection of mast cells with reporter genes by electroporation. These protocols should be widely applicable in mast cell research.

Impact of prognostic factors on long-term outcomes in metastatic breast cancer (MBC) patients (pts) receiving bevacizumab (B) plus paclitaxel as firs…

2014

e12007 Background: B combined with chemotherapy (CT) significantly improves progression-free survival (PFS) and response rate (RR) vs CT alone in the first-line treatment of HER2-negative MBC. In a...

Rīgas Politehnikuma studentu disciplinēšanas regula

2022

Raksts ir tapis Studentu karcera ilgtermiņa pētnieciskā darba ietvaros, kur par pētāmo objektu izvēlēts Rīgas Politehnikuma/Rīgas Politehniskā institūta Studentu disciplinēšanas regulu. Tiek analizēti regulas panti Studentu karcera kontekstā, lai izvērtētu to formalitātes sakritību un nesakritību ar faktisko situāciju, konstatējot atšķirības studentu soda termiņu noteikšanā. Arī tiek veidotas paralēles ar analogu Studentu karceri, kas atrodas Heidelbergas universitātē, izšķirot kopīgo un atšķirīgo studentu karcera ieslēgšanas iemeslos, studentu etniskajā sastāvā, telpu iekārtojumā un sadzīves apstākļos.