scholarly journals Mycobacterium tuberculosis secretory proteins downregulate T cell activation by interfering with proximal and downstream T cell signalling events

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Bhawna Sharma ◽  
Rajni Upadhyay ◽  
Bhavyata Dua ◽  
Naim Akhtar Khan ◽  
Vishwa Mohan Katoch ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Signalling ◽  
Secretory Proteins ◽  
T Cell Signalling

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+.

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.

Immunogenic membrane-associated proteins of Mycobacterium tuberculosis revealed by proteomics

Microbiology ◽  
2005 ◽  
Vol 151 (7) ◽  
pp. 2411-2419 ◽  
Author(s):  
Sudhir Sinha ◽  
K. Kosalai ◽  
Shalini Arora ◽  
Abdelkader Namane ◽  
Pawan Sharma ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Activation ◽  
Gel Electrophoresis ◽  
Ribosomal Proteins ◽  
Cell Activation ◽  
Flight Mass Spectrometry ◽  
Peptide Mass ◽  
Mass Fractions ◽  
Associated Proteins

Membrane-associated proteins of Mycobacterium tuberculosis offer a challenge, as well as an opportunity, in the quest for better therapeutic and prophylactic interventions against tuberculosis. The authors have previously reported that extraction with the detergent Triton X-114 (TX-114) is a useful step in proteomic analysis of mycobacterial cell membranes, and detergent-soluble membrane proteins of mycobacteria are potent stimulators of human T cells. In this study 1-D and 2-D gel electrophoresis-based protocols were used for the analysis of proteins in the TX-114 extract of M. tuberculosis membranes. Peptide mass mapping (using MALDI-TOF-MS, matrix assisted laser desorption/ionization time of flight mass spectrometry) of 116 samples led to the identification of 105 proteins, 9 of which were new to the M. tuberculosis proteome. Functional orthologues of 73 of these proteins were also present in Mycobacterium leprae, suggesting their relative importance. Bioinformatics predicted that as many as 73 % of the proteins had a hydrophobic disposition. 1-D gel electrophoresis revealed more hydrophobic/transmembrane and basic proteins than 2-D gel electrophoresis. Identified proteins fell into the following major categories: protein synthesis, cell wall biogenesis/architecture and conserved hypotheticals/unknowns. To identify immunodominant proteins of the detergent phase (DP), 14 low-molecular-mass fractions prepared by continuous-elution gel electrophoresis were subjected to T cell activation assays using blood samples from BCG-vaccinated healthy donors from a tuberculosis endemic area. Analysis of the responses (cell proliferation and IFN-γ production) showed that the immunodominance of certain DP fractions was most probably due to ribosomal proteins, which is consistent with both their specificity for mycobacteria and their abundance. Other membrane-associated proteins, including transmembrane proteins/lipoproteins and ESAT-6, did not appear to contribute significantly to the observed T cell responses.

scholarly journals CD4+ T-Cell Subsets That Mediate Immunological Memory to Mycobacterium tuberculosis Infection in Mice

2000 ◽  
Vol 68 (2) ◽  
pp. 621-629 ◽  
Author(s):  
Peter Andersen ◽  
Birgitte Smedegaard
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immunological Memory ◽  
T Cell Subsets ◽  
Small Subset ◽  
Memory Cells ◽  
Activation Markers

ABSTRACT We have studied CD4+ T cells that mediate immunological memory to an intravenous infection with Mycobacterium tuberculosis. The studies were conducted with a mouse model of memory immunity in which mice are rendered immune by a primary infection followed by antibiotic treatment and rest. Shortly after reinfection, tuberculosis-specific memory cells were recruited from the recirculating pool, leading to rapidly increasing precursor frequencies in the liver and a simultaneous decrease in the blood. A small subset of the infiltrating T cells was rapidly activated (<20 h) and expressed high levels of intracellular gamma interferon and the T-cell activation markers CD69 and CD25. These memory effector T cells expressed intermediate levels of CD45RB and were heterogeneous with regard to the L-selectin and CD44 markers. By adoptive transfer into nude mice, the highest level of resistance to a challenge with M. tuberculosis was mediated by CD45RBhigh,l-selectinhigh, CD44low cells. Taken together, these two lines of evidence support an important role for memory cells which have reverted to a naive phenotype in the long-term protection against M. tuberculosis.

scholarly journals Lung Epithelial Signaling Mediates Early Vaccine-Induced CD4 + T Cell Activation and Mycobacterium tuberculosis Control

mBio ◽  
2021 ◽  
Author(s):  
Shibali Das ◽  
Nancy D. Marin ◽  
Ekaterina Esaulova ◽  
Mushtaq Ahmed ◽  
Amanda Swain ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Cause Of Death ◽  
T Cell Activation ◽  
Cell Activation ◽  
Infectious Agent ◽  
Cd4 T Cell ◽  
Tuberculosis Control ◽  
Lung Epithelial

Tuberculosis is a leading cause of death due to single infectious agent accounting 1.4 million deaths each year. The only licensed vaccine, BCG, is not effective due to variable efficacy.

scholarly journals Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection

2020 ◽  
Author(s):  
Cheleka A.M. Mpande ◽  
Virginie Rozot ◽  
Boitumelo Mosito ◽  
Munyaradzi Musvosvi ◽  
One B Dintwe ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Differentially Expressed ◽  
Cd4 T Cell ◽  
Remote Infection ◽  
Ifn Γ

AbstractBackgroundRecent Mycobacterium tuberculosis (M.tb) infection is associated with a higher risk of progression to tuberculosis disease, compared to persistent infection after remote exposure. However, current immunodiagnostic tools fail to distinguish between recent and remote infection. We aimed to characterise the immunobiology associated with acquisition of M.tb infection and identify a biomarker that can distinguish recent from remote infection.MethodsHealthy South African adolescents were serially tested with QuantiFERON-TB Gold to define recent (QuantiFERON-TB conversion <6 months) and persistent (QuantiFERON-TB+ for >1.5 year) infection. We characterized M.tb-specific CD4 T cell functional (IFN-γ, TNF, IL-2, CD107, CD154), memory (CD45RA, CCR7, CD27, KLRG-1) and activation (HLA-DR) profiles by flow cytometry after CFP-10/ESAT-6 peptide pool or M.tb lysate stimulation. We then assessed the diagnostic performance of immune profiles that were differentially expressed between individuals with recent or persistent QuantiFERON-TB+.FindingsCFP-10/ESAT-6-specific CD4 T cell activation but not functional or memory phenotypes distinguished between individuals with recent and persistent QuantiFERON-TB+. In response to M.tb lysate, recent QuantiFERON-TB+ individuals had lower proportions of highly differentiated IFN-γ+TNF+ CD4 T cells expressing a KLRG-1+ effector phenotype and higher proportions of early differentiated IFN-γ-TNF+IL-2+ and activated CD4 T cells compared to persistent QuantiFERON-TB+ individuals. Among all differentially expressed T cell features CFP-10/ESAT-6-specific CD4 T cell activation was the best performing diagnostic biomarker of recent infection.InterpretationRecent M.tb infection is associated with highly activated and moderately differentiated functional M.tb-specific T cell subsets, that can be used as biomarkers to distinguish between recent and remote infection.

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