On a Formal Model of the T Cell and Its Biological Feedback

2011 ◽  
pp. 224-242
Author(s):  
Gabriel Ciobanu
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Formal Model ◽  
Discrete Event ◽  
Software Tool ◽  
Hierarchical Organization ◽  
Biological Information ◽  
Cell Behaviour ◽  
Immunological Responses ◽  
T Cell Signalling

In this chapter a model of the molecular networks, created by using a network of communicating automata, is described as a dynamic structure, discrete event system, and interesting theoretical results are provided. This formal model provides a detailed approach of the biological system, and its implementation is able to handle large amounts of data. This model is applied to T cell signalling networks. T cell shows a hierarchical organization depending on various factors. Some mechanisms are still unresolved, including contribution of each signalling pathway to each response type. The software tool produced is used to simulate and analyze the T cell behaviour. The simulation reflects, quite faithfully, the process of T cell activation and T cell responses. This increases the confidence in using this model and its implementation both as descriptive and prescriptive tools. The interactions that govern the T cell behaviour are simulated and analyzed, providing statistical correlations according to software experiments, together with new insights on signalling networks that trigger immunological responses. The software tool allows users to systematically perturb and monitor the components of a T cell molecular network, capturing biological information relevant to immunology.

scholarly journals Submicromolar La3+ concentrations block the calcium release-activated channel, and impair CD69 and CD25 expression in CD3- or thapsigargin-activated Jurkat cells

1996 ◽  
Vol 313 (3) ◽  
pp. 909-913 ◽  
Author(s):  
Claude AUSSEL ◽  
Rachid MARHABA ◽  
Claudette PELASSY ◽  
Jean-Philippe BREITTMAYER
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Calcium Release ◽  
Cell Signalling ◽  
Interleukin 2 ◽  
Jurkat Cells ◽  
T Cell Signalling ◽  
A Chain ◽  
20 Nm

The calcium release-activated channel (CRAC) opened in Jurkat cells activated either with CD3 monoclonal antibody or the endoplasmic reticulum Ca2+-ATPase blocker, thapsigargin, is blocked by La3+ with an IC50 of 20 nM. Similarly, the entry of Mn2+, used as a surrogate for Ca2+, is also blocked by submicromolar La3+ concentrations. La3+ seems to play its role simply by plugging the CRAC because this ion does not penetrate the cells, as demonstrated by chelation experiments with EGTA. Blocking the Ca2+ influx in activated Jurkat cells results in a lack of expression of CD25, a chain of the interleukin-2 receptor and of CD69, a marker of T-cell activation. By contrast, the very early steps of the T-cell signalling pathway such as the release of Ca2+ from intracellular stores and the subsequent inhibition of phosphatidylserine synthesis are not affected by La3+.

scholarly journals Integrated immune networks in SARS-CoV-2 infected pregnant women reveal differential NK cell and unconventional T cell activation

2021 ◽  
Author(s):  
Jennifer R Habel ◽  
Brendon Y Chua ◽  
Lukasz Kedzierski ◽  
Kevin J Selva ◽  
Timon Damelang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Pregnant Women ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nk Cell ◽  
Γδ T Cells ◽  
Immunological Parameters ◽  
Immunological Responses ◽  
Mait Cells

ABSTRACTAlthough pregnancy poses a greater risk for severe COVID-19, the underlying immunological changes associated with SARS-CoV-2 infection during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in pregnant and non-pregnant women during acute and convalescent COVID-19 up to 258 days post symptom onset, quantifying 217 immunological parameters. Additionally, matched maternal and cord blood were collected from COVID-19 convalescent pregnancies. Although serological responses to SARS-CoV-2 were similar in pregnant and non-pregnant women, cellular immune analyses revealed marked differences in key NK cell and unconventional T cell responses during COVID-19 in pregnant women. While NK cells, γδ T cells and MAIT cells displayed pre-activated phenotypes in healthy pregnant women when compared to non-pregnant age-matched women, activation profiles of these pre-activated NK and unconventional T cells remained unchanged at acute and convalescent COVID-19 in pregnancy. Conversely, activation dynamics of NK and unconventional T cells were prototypical in non-pregnant women in COVID-19. In contrast, activation of αβ CD4+ and CD8+ T cells, T follicular helper cells and antibody-secreting cells was similar in pregnant and non-pregnant women with COVID-19. Elevated levels of IL-1β, IFN-γ, IL-8, IL-18 and IL-33 were also found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, our study provides the first comprehensive map of longitudinal immunological responses to SARS-CoV-2 infection in pregnant women, providing insights into patient management and education during COVID-19 pregnancy.

scholarly journals RNA Sequencing to Explore Dominant Isoform Switch During CCR6+ Memory T Cell Activation

2021 ◽  
Author(s):  
Shanrong Zhao ◽  
Alexander Barron ◽  
Ken Dower
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Rna Sequencing ◽  
T Cell Activation ◽  
Cell Cycle Progression ◽  
Cell Activation ◽  
Cell Function ◽  
Control Cell ◽  
Biological Information ◽  
Rna Seq

Abstract Alternative splicing (AS) is an essential, but under-investigated component of T-cell function during immune responses. Recent developments in RNA sequencing (RNA-seq) technologies, combined with the advent of computational tools, have enabled transcriptome-wide studies of AS at an unprecedented scale and resolution. In this paper, we analysed AS in an RNA-seq dataset previously generated to investigate the expression changes during T-cell maturation and antigen stimulation. Eight genes were identified with their most dominant isoforms switched during T cell activation. Of those, seven genes either directly control cell cycle progression or are oncogenes. We selected CDKN2C, FBXO5, NT5E and NET1 for discussion of the functional importance of AS of these genes. Our case study demonstrates that combining AS and gene expression analyses derives greater biological information and deeper insights from RNA-seq datasets than gene expression analysis alone.

scholarly journals Integrated immune networks in SARS-CoV-2 infected pregnant women reveal differential NK cell and unconventional T cell activation

2021 ◽  
Author(s):  
Katherine Kedzierska ◽  
Jennifer Habel ◽  
Brendon Chua ◽  
Lukasz Kedzierski ◽  
Kevin Selva ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Pregnant Women ◽  
T Cell Activation ◽  
Cell Activation ◽  
Nk Cell ◽  
Γδ T Cells ◽  
Immunological Parameters ◽  
Immunological Responses ◽  
Mait Cells

Abstract Although pregnancy poses a greater risk for severe COVID-19, the underlying immunological changes associated with SARS-CoV-2 infection during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in pregnant and non-pregnant women during acute and convalescent COVID-19 up to 258 days post symptom onset, quantifying 217 immunological parameters. Additionally, matched maternal and cord blood were collected from COVID-19 convalescent pregnancies. Although serological responses to SARS-CoV-2 were similar in pregnant and non-pregnant women, cellular immune analyses revealed marked differences in key NK cell and unconventional T cell responses during COVID-19 in pregnant women. While NK, γδ T cells and MAIT cells displayed pre-activated phenotypes in healthy pregnant women when compared to non-pregnant age-matched women, activation profiles of these pre-activated NK and unconventional T cells remained unchanged at acute and convalescent COVID-19 in pregnancy. Conversely, activation dynamics of NK and unconventional T cells were prototypical in non-pregnant women in COVID-19. In contrast, activation of αβ CD4+ and CD8+ T cells, T follicular helper cells and antibody-secreting cells was similar in pregnant and non-pregnant women with COVID-19. Elevated levels of IL-1β, IFN-γ, IL-8, IL-18 and IL-33 were also found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, our study provides the first comprehensive map of longitudinal immunological responses to SARS-CoV-2 infection in pregnant women, providing insights into patient management and education during COVID-19 pregnancy.

Protein kinase Cθ: the pleiotropic T-cell signalling intermediate

2014 ◽  
Vol 42 (6) ◽  
pp. 1512-1518 ◽  
Author(s):  
Katarzyna Wachowicz ◽  
Gottfried Baier
Keyword(s):  
T Cell ◽  
Protein Kinase ◽  
T Cell Activation ◽  
Th17 Cell ◽  
Cell Activation ◽  
Cell Signalling ◽  
Cell Receptor ◽  
Cell Phenotype ◽  
Inhibitory Circuits ◽  
T Cell Signalling

Activating as well as inhibitory circuits tightly regulate T-cell activation thresholds and effector differentiation processes enabling proper immune response outcomes. Recently, an additional molecular link between T-cell receptor signalling and CD4+ Th17 cell skewing has been reported, namely that protein kinase C (PKC) θ critically regulates Th17/Th1 phenotypic differentiation and plasticity in CD4+ T-cells by selectively acting as a ‘reprogramming element’ that suppresses Th1-typical genes during Th17-mediated immune activation in order to stabilize a Th17 cell phenotype.

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