The influence of cyclosporin A on T cell activation, cytokine gene expression and cell-mediated immunity

Cyclosporin ◽  
1989 ◽  
pp. 50-81 ◽  
Author(s):  
Angus W. Thomson ◽  
Janet I. Duncan
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Cyclosporin A ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytokine Gene Expression ◽  
Cell Mediated Immunity ◽  
Cytokine Gene

scholarly journals Arginine methylation regulates IL-2 gene expression: a role for protein arginine methyltransferase 5 (PRMT5)

2005 ◽  
Vol 388 (1) ◽  
pp. 379-386 ◽  
Author(s):  
Stéphane RICHARD ◽  
Mélanie MOREL ◽  
Patrick CLÉROUX
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Arginine Methylation ◽  
Cytokine Gene Expression ◽  
Luciferase Reporter ◽  
Protein Arginine Methylation

Arginine methylation is a post-translational modification resulting in the generation of aDMAs (asymmetrical ω-NG, NG-dimethylated arginines) and sDMAs (symmetrical ω-NG, N′G-dimethylated arginines). The role of arginine methylation in cell signalling and gene expression in T lymphocytes is not understood. In the present study, we report a role for protein arginine methylation in regulating IL-2 (interleukin 2) gene expression in T lymphocytes. Leukaemic Jurkat T-cells treated with a known methylase inhibitor, 5′-methylthioadenosine, had decreased cytokine gene expression, as measured using an NF-AT (nuclear factor of activated T-cells)-responsive promoter linked to the luciferase reporter gene. Since methylase inhibitors block all methylation events, we performed RNA interference with small interfering RNAs against the major PRMT (protein arginine methyltransferases) that generates sDMA (PRMT5). The dose-dependent decrease in PRMT5 expression resulted in the inhibition of both IL-2- and NF-AT-driven promoter activities and IL-2 secretion. By using an sDMA-specific antibody, we observed that sDMA-containing proteins are directly associated with the IL-2 promoter after T-cell activation. Since changes in protein arginine methylation were not observed after T-cell activation in Jurkat and human peripheral blood lymphocytes, our results demonstrate that it is the recruitment of methylarginine-specific protein(s) to cytokine promoter regions that regulates their gene expression.

scholarly journals Vitamin D Supplementation Modulates T Cell–Mediated Immunity in Humans: Results from a Randomized Control Trial

2016 ◽  
Vol 101 (2) ◽  
pp. 533-538 ◽  
Author(s):  
Gauree Gupta Konijeti ◽  
Pankaj Arora ◽  
Matthew R. Boylan ◽  
Yanna Song ◽  
Shi Huang ◽  
...  
Keyword(s):  
Vitamin D ◽  
T Cell ◽  
Vitamin D Deficiency ◽  
T Cell Activation ◽  
Vitamin D3 ◽  
Cell Activation ◽  
Atp Release ◽  
High Dose ◽  
Cell Mediated Immunity ◽  
Ancillary Study

Abstract Context: Although studies have linked vitamin D deficiency with immune-mediated diseases, data demonstrating a direct effect on T-cell function are sparse. Objective: Our objective was to determine whether oral vitamin D3 influences T-cell activation in humans with vitamin D deficiency. Design: This was a single-center ancillary study within Vitamin D Therapy in Individuals at High Risk of Hypertension, a double-blind, multicenter, randomized controlled trial. Setting: This study was undertaken in a single academic medical center. Participants: Adults with vitamin D deficiency and untreated pre- or early stage I hypertension were included. Intervention: In Vitamin D Therapy in Individuals at High Risk of Hypertension, participants were randomized to either low- (400 IU daily) or high- (4000 IU daily) dose oral vitamin D3 for 6 months. In this ancillary study of 38 patients, we measured CD4+ T-cell activation estimated by intracellular ATP release after stimulation of whole blood with plant lectin phytohemagglutinin collected at baseline (pretreatment) and 2-month follow-up. Main Outcome Measure: Determining whether ATP level changes were significantly different between treatment groups was the main outcome measure. Results: Treatment with 4000 IU of vitamin D3 decreased intracellular CD4+ ATP release by 95.5 ng/ml (interquartile range, −219.5 to 105.8). In contrast, 400 IU of vitamin D3 decreased intracellular CD4+ ATP release by 0.5 ng/ml (interquartile range, −69.2 to 148.5). In a proportional odds model, high-dose vitamin D3 was more likely than low-dose vitamin D3 to decrease CD4+ ATP release (odds ratio, 3.43; 95% confidence interval, 1.06–1.11). Conclusions: In this ancillary study of a randomized controlled trial, we found that high-dose vitamin D3 significantly reduced CD4+ T-cell activation compared to low-dose vitamin D3, providing human evidence that vitamin D can influence cell-mediated immunity.

scholarly journals Regulation of translation initiation factor gene expression during human T cell activation.

1992 ◽  
Vol 267 (28) ◽  
pp. 20444-20450
Author(s):  
X Mao ◽  
J.M. Green ◽  
B Safer ◽  
T Lindsten ◽  
R.M. Frederickson ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Cell Activation ◽  
Translation Initiation ◽  
Cell Activation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Factor Gene ◽  
Regulation Of Translation ◽  
Human T Cell

Distinct Neopterin Excretion Patterns after Vaccination

Pteridines ◽  
1990 ◽  
Vol 2 (3) ◽  
pp. 147-149 ◽  
Author(s):  
Dietmar Fuchs ◽  
Arno Hausen ◽  
Gilbert Reibnegger ◽  
Ernst R. Werner ◽  
Gabriele Werner-Felmayer ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cellular Immunity ◽  
Tetanus Toxoid ◽  
Cell Activation ◽  
Cell Mediated Immunity ◽  
Soluble Antigen ◽  
Human Monocytes ◽  
Mumps Vaccine ◽  
Urinary Neopterin

Summary To compare the involvement of cellular immunity in response to vaccination we have investigated urinary neopterin levels in daily follow-ups of children after vaccination with live measles/mumps vaccine and of adults after boosting with the soluble antigen tetanus toxoid. Neopterin levels distinctly peaked 8 - 11 days after vaccination with measles/mumps vaccine. In contrast, after boosting with soluble antigen tetanus toxoid neopterin levels remained unaffected. Large amounts of neopterin are produced by human monocytes/ macro phages on stimulation with gamma interferon. In patients neopterin concentrations reflect activation of cell mediated immunity. The data imply that distinct pathways of T cell activation are triggered in humans after immunization with live vaccine and with soluble antigen .

T.69. T Cell Activation and Th2-related Gene Expression Correlate with Disease Activity in Glatiramer Acetate-treated Multiple Sclerosis

2009 ◽  
Vol 131 ◽  
pp. S70
Author(s):  
Finn Sellebjerg ◽  
Martin Krakauer ◽  
Dan Hesse ◽  
Henrik Lund ◽  
Signe Limborg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
T Cell ◽  
Disease Activity ◽  
Glatiramer Acetate ◽  
T Cell Activation ◽  
Cell Activation ◽  
Related Gene

scholarly journals Nanoconfinement of Microvilli Alters Gene Expression and Boosts T cell Activation

2021 ◽  
Author(s):  
Morteza Aramesh ◽  
Diana Stoycheva ◽  
Ioana Sandu ◽  
Stephan J. Ihle ◽  
Tamara Zund ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Cell Signaling ◽  
T Cell Activation ◽  
Cell Activation ◽  
Local Environment ◽  
T Cell Signaling ◽  
Sense And Respond ◽  
Altered Gene

T cells sense and respond to their local environment at the nanoscale by forming small actin-rich protrusions, called microvilli, which play critical roles in signaling and antigen recognition, particularly at the interface with the antigen presenting cells. However, the mechanisms by which microvilli contribute to cell signaling and activation is largely unknown. Here, we present a tunable engineered system that promotes microvilli formation and T cell signaling via physical stimuli. We discovered that nanoporous surfaces favored microvilli formation, and markedly altered gene expression in T cells and promoted their activation. Mechanistically, confinement of microvilli inside of nanopores leads to size-dependent sorting of membrane-anchored proteins, specifically segregating CD45 phosphatases and T cell receptors (TCR) from the tip of the protrusions when microvilli are confined in 200 nm pores, but not in 400 nm pores. Consequently, formation of TCR nanoclustered hotspots within 200 nm pores, allows sustained and augmented signaling that prompts T cell activation even in the absence of TCR agonists. The synergistic combination of mechanical and biochemical signals on porous surfaces presents a straightforward strategy to investigate the role of microvilli in T cell signaling as well as to boost T cell activation and expansion for application in the growing field of adoptive immunotherapy.

scholarly journals SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell–mediated immunity

Science ◽  
2021 ◽  
Vol 372 (6543) ◽  
pp. eaba4220 ◽  
Author(s):  
Tao Yue ◽  
Xiaoming Zhan ◽  
Duanwu Zhang ◽  
Ruchi Jain ◽  
Kuan-wen Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Cell Mediated Immunity ◽  
Activated T Cells ◽  
Granule Formation

Reactive oxygen species (ROS) increase in activated T cells because of metabolic activity induced to support T cell proliferation and differentiation. We show that these ROS trigger an oxidative stress response that leads to translation repression. This response is countered by Schlafen 2 (SLFN2), which directly binds transfer RNAs (tRNAs) to protect them from cleavage by the ribonuclease angiogenin. T cell–specific SLFN2 deficiency results in the accumulation of tRNA fragments, which inhibit translation and promote stress-granule formation. Interleukin-2 receptor β (IL-2Rβ) and IL-2Rγ fail to be translationally up-regulated after T cell receptor stimulation, rendering SLFN2-deficient T cells insensitive to interleukin-2’s mitogenic effects. SLFN2 confers resistance against the ROS-mediated translation-inhibitory effects of oxidative stress normally induced by T cell activation, permitting the robust protein synthesis necessary for T cell expansion and immunity.

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