Search results for "T cell"

T cell-independent joint destruction

1998

Rheumatoid Arthritis (RA) is a chronic systemic disorder of unknown etiology. Although, early and late stages of the disease may be driven by different processes, affected joints are characterized by inflammation, synovial hyperplasia, and abnormal immune responses [1]. The abundance of T cells within the rheumatoid synovium as well as the association of certain major histocompatibility complex (MHC) class II molecules with RA [2] implied a central role for T cells in the pathophysiology of the disease. However, recent advances in molecular biology have fostered new concepts for the pathogenesis of RA. Specifically, the investigation of early stages of disease, the development of novel anim…

Antiproliferative Properties of a Few Auranofin-Related Gold(I) and Silver(I) Complexes in Leukemia Cells and their Interferences with the Ubiquitin …

2020

A group of triethylphosphine gold(I) and silver(I) complexes, structurally related to auranofin, were prepared and investigated as potential anticancer drug candidates. The antiproliferative properties of these metal compounds were assessed against two leukemia cell lines, i.e., CCRF-CEM and its multidrug-resistant counterpart, CEM/ADR5000. Interestingly, potent cytotoxic effects were disclosed for both series of compounds against leukemia cells, with IC50 values generally falling in the low-micromolar range, the gold derivatives being on the whole more effective than the silver analogues. Some initial structure-function relationships were drawn. Subsequently, the ability of the study compo…

Detection of proteolytic (C 3-cleaving) activity on mouse mastocytoma (P815) cells and other mouse cell lines by formation of cell contact with C 3-c…

1979

Mouse mastocytoma cells (P 815) formed rosettes with normal mouse spleen lymphocytes which had been coated with uncleaved human C 3; this interaction was clearly dependent on the amount of C 3. Lymphocytes treated with C 3 b or buffer alone were ineffective. Formation of cell contact could be inhibited by the presence of protease inhibitors such as diisopropyl fluorophosphate, phenyl methyl sulfonyl fluoride and tosyllysyl chloromethyl ketone. Seve n out of 13 different cell lines behaved like P 815 cells. The results strongly suggested that a proteolytic activity on mouse tumor cells led to a cooperation with uncleaved C 3 on a carrier cell to connect these two cells. We interpreted these …

Priming of Leishmania-Reactive CD8+ T cells In Vivo Does Not Require LMP7-Containing Immunoproteasomes

2012

Proteasomes shape the repertoire of T cells participating in antigen-specific immune responses

2006

Differences in the cleavage specificities of constitutive proteasomes and immunoproteasomes significantly affect the generation of MHC class I ligands and therefore the activation of CD8-positive T cells. Based on these findings, we investigated whether proteasomal specificity also influences CD8-positive T cells during thymic selection by peptides derived from self proteins. We find that one of the self peptides responsible for positive selection of ovalbumin-specific OT-1 T cells, which is derived from the f-actin capping protein (Cpalpha1), is efficiently generated only by immunoproteasomes. Furthermore, OT-1 mice backcrossed onto low molecular mass protein 7 (LMP7)-deficient mice show a…

Immunomodulating role of bisphosphonates on human gamma delta T cells: an intriguing and promising aspect of their antitumour activity.

2007

Vgamma9Vdelta2 T cells have the ability to produce inflammatory cytokines involved in protective immunity against intracellular pathogens and tumours and to display strong cytolytic as well as bactericidal activities. This suggests a direct involvement of Vgamma9Vdelta2 T lymphocytes in immune control of cancer and infections. These observations have recently aided development of novel immunotherapeutic approaches aimed at Vgamma9Vdelta2 T cell activation. Nitrogen-containing bisphosphonates (N-BPs) play a crucial role in Vgamma9Vdelta2 T lymphocyte activation and in the acquisition of effector functions. The preliminary results of these innovative strategies are encouraging. Moreover, comp…

Direct evidence that FK506 inhibition of FcεRI-mediated exocytosis from RBL mast cells involves calcineurin

1998

eRI-mediated exocytosis of preformed mediators from mast cells and basophils (e.g. histamine, serotonin, beta-hexosaminidase) is sensitive to the immunosuppressants cyclosporin A and FK506 (IC 50 200 and 4 n M , respectively) but not rapamycin. The mechanism of inhibition does not appear to involve tyrosine phosphorylation, hydrolysis of inositol phosphates or calcium flux. Here we report experiments using a molecular approach to assess the role of calcineurin, a serine/threonine phosphatase thought to be the primary pharmacological target of these drugs. Calcineurin’s activity requires association of its catalytic (A) subunit with an intrinsic regulatory (B) subunit. We hypothesized that c…

B7/CD28 costimulation of T cells induces a distinct proteome pattern.

2005

Effective immune strategies for the eradication of human tumors require a detailed understanding of the interaction of tumor cells with the immune system, which might lead to an optimization of T cell responses. To understand the impact of B7-mediated costimulation on T cell activation comprehensive proteome analysis of B7-primed T cell populations were performed. Using this approach we identified different classes of proteins in T cells whose expression is either elevated or reduced upon B7-1- or B7-2-mediated CD28 costimulation. The altered proteins include regulators of the cell cycle and cell proliferation, signal transducers, components of the antigen processing machinery, transporters…

Biological properties of extracellular vesicles and their physiological functions

2015

The authors wish to thank Dr R Simpson and Dr D Taylor for critical reading of the manuscript and acknowledge the Horizon 2020 European Cooperation in Science and Technology programme and its support of our European Network on Microvesicles and Exosomes in Health & Disease (ME-HaD; BM1202 www.cost.eu/COST_Actions/bmbs/Actions/BM1202). In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive invest…

Mitochondrial proteomics profile points oxidative phosphorylation as main target for beauvericin and enniatin B mixture

2020

Abstract Beauvericin (BEA) and enniatin B (EN B) are non-legislated Fusarium mycotoxins usually found in cereal and cereal-based products all around the world. By the proteomic analysis of mitochondria enriched extracts from Jurkat cells exposed for 24 h to three concentrations of BEA:EN B (0.01–0.1–0.5 μM), a number of 1821 proteins (202 mitochondrial) were identified and relatively quantified. 340 proteins (59 mitochondrial) were statistically significant altered in our samples (Anova p-value ≤ 0.05 and fold change (FC) ≥1.5). The protein mitochondrial translational release factor 1 like (MTRF1L) was the most abundant protein in the three mycotoxin exposures studied. The mycotoxins mixtur…