scholarly journals Alterations in the human plasma lipidome in response to Tularemia vaccination

2020 ◽  
Author(s):  
Kristal M. Maner-Smith ◽  
David A. Ford ◽  
Johannes B. Goll ◽  
Travis L. Jensen ◽  
Manoj Khadka ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Lipid Classes ◽  
Vaccine Response ◽  
Fatal Disease ◽  
Post Vaccination ◽  
Lipid Molecular Species ◽  
Lipid Species ◽  
Tularemia Vaccine ◽  
Kinetics Of

AbstractTularemia is a rare but highly contagious and potentially fatal disease caused by bacteria Francisella tularensis where as few as ten inhaled organisms can lead to an infection, making it one of the most infectious microorganisms known and a potential bioweapon. To better understand the response to a live, attenuated tularemia vaccine and the biological pathways altered post-vaccination, healthy adults were vaccinated by scarification and plasma was collected pre- and post-vaccination for longitudinal lipidomics studies. Using tandem mass spectrometry, we identified and quantified individual lipid molecular species within representative lipid classes in plasma to characterize alterations in the plasma lipidome during the vaccine response. Separately, we targeted oxylipins, a subset of lipid mediators involved in inflammatory pathways. We identified 14 differentially abundant lipid species from eight lipid classes. These included 5-Hydroxyeicosatetraenoic acid (5-HETE), an eicosanoid produced following arachidonic acid liberation and epoxygenation, which is indicative of lipoxygenase activity and, subsequently, inflammation. Results suggest that 5-HETE was metabolized to a dihydroxyeicosatrienoic acid (DHET) by Day 7 post-vaccination, shedding light on the kinetics of the 5-HETE-mediated inflammatory response. In addition to 5-HETE and DHET, we observed pronounced changes in 34:1 phosphatidylinositol, anandamide, oleamide, ceramides, 16:1 cholesteryl ester, and several glycerophospholipids, several of these changes in abundance were correlated with serum cytokines and T cell activation. These data provide new insights into alterations in plasma lipidome post tularemia vaccination, potentially identifying key mediators and pathways involved in vaccine response and efficacy.

scholarly journals Alterations in the Human Plasma Lipidome in Response to Tularemia Vaccination

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 414
Author(s):  
Kristal M. Maner-Smith ◽  
Johannes B. Goll ◽  
Manoj Khadka ◽  
Travis L. Jensen ◽  
Jennifer K. Colucci ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Lipid Classes ◽  
Human Response ◽  
Vaccine Response ◽  
Post Vaccination ◽  
Serum Cytokines ◽  
Lipid Species ◽  
Tularemia Vaccine ◽  
Kinetics Of

Tularemia is a highly infectious and contagious disease caused by the bacterium Francisella tularensis. To better understand human response to a live-attenuated tularemia vaccine and the biological pathways altered post-vaccination, healthy adults were vaccinated, and plasma was collected pre- and post-vaccination for longitudinal lipidomics studies. Using tandem mass spectrometry, we fully characterized individual lipid species within predominant lipid classes to identify changes in the plasma lipidome during the vaccine response. Separately, we targeted oxylipins, a subset of lipid mediators involved in inflammatory pathways. We identified 14 differentially abundant lipid species from eight lipid classes. These included 5-hydroxyeicosatetraenoic acid (5-HETE) which is indicative of lipoxygenase activity and, subsequently, inflammation. Results suggest that 5-HETE was metabolized to a dihydroxyeicosatrienoic acid (DHET) by day 7 post-vaccination, shedding light on the kinetics of the 5-HETE-mediated inflammatory response. In addition to 5-HETE and DHET, we observed pronounced changes in 34:1 phosphatidylinositol, anandamide, oleamide, ceramides, 16:1 cholesteryl ester, and other glycerophospholipids; several of these changes in abundance were correlated with serum cytokines and T cell activation. These data provide new insights into alterations in plasma lipidome post-tularemia vaccination, potentially identifying key mediators and pathways involved in vaccine response and efficacy.

Controlling receptor-ligand contact to examine kinetics of T cell activation

1997 ◽  
Vol 25 (6) ◽  
pp. 1072-1080 ◽  
Author(s):  
S. M. Patrick ◽  
H. An ◽  
M. B. Harris ◽  
I. B. Ivanov ◽  
N. S. Braunstein ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Receptor Ligand ◽  
Kinetics Of

Kinetics of T Cell Activation Are Altered in the Presence of Cancer

2010 ◽  
Vol 158 (2) ◽  
pp. 400-401
Author(s):  
A.J. Russ ◽  
L. Wentworth ◽  
C.S. Cho
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Kinetics Of

scholarly journals Metabolic turnover and dynamics of RNA modifications by 13C labelling

2021 ◽  
Author(s):  
Paulo A Gameiro ◽  
Iosifina Foskolou ◽  
Vesela Encheva ◽  
Mariana Silva dos Santos ◽  
James MacRae ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Mammalian Cells ◽  
Quantitative Methods ◽  
Cell Activation ◽  
Metabolic Stress ◽  
Rna Modifications ◽  
Biological Regulation ◽  
Rna Methylation ◽  
Ribonucleoprotein Complexes ◽  
Kinetics Of

Abstract RNA methylation is essential for appropriate assembly of ribonucleoprotein complexes. Dynamics of RNA methylation is thus important, but we lack quantitative methods to comprehensively assess it. We developed 13C-dynamods, an isotopic labelling approach using 13C-methyl-methionine, to quantify the turnover of base modifications in newly synthesized RNA, which is effective in distinguishing modifications in mRNAs from those in ncRNAs. This approach detected the presence of N6,N6-dimethyladenosine (m62A) in mRNA and tRNA in mammalian cells, and uncovered distinct kinetics of N-6-methyladenosine (m6A) and N-7-methylguanosine (m7G) in mRNA. Moreover, by assessing RNA metabolism during T-cell activation, we showed how methylation dynamics is coordinated with ribonucleotide biosynthesis. Finally, by quantification of methylation turnover and ribonucleoside abundance, we uncover the post-transcriptional lability of m6A in response to metabolic stress. Thus, 13C-dynamods enables studies of the origin, maintenance and biological regulation of RNA modifications under steady-state and non-stationary conditions.

The role of lipid rafts in signalling and membrane trafficking in T lymphocytes

2001 ◽  
Vol 114 (22) ◽  
pp. 3957-3965
Author(s):  
Miguel A. Alonso ◽  
Jaime Millán
Keyword(s):  
T Lymphocytes ◽  
Epithelial Cells ◽  
Lipid Rafts ◽  
T Cell Activation ◽  
Membrane Trafficking ◽  
Intracellular Transport ◽  
Cell Activation ◽  
Membrane Microdomains ◽  
Caveolin 1 ◽  
Lipid Species

Combinatorial association of different lipid species generates microheterogeneity in biological membranes. The association of glycosphingolipids with cholesterol forms membrane microdomains – lipid rafts – that are involved in specialised pathways of protein/lipid transport and signalling. Lipid rafts are normally dispersed in cellular membranes and appear to require specialised machinery to reorganise them to operate. Caveolin-1 and MAL are members of two different protein families involved in reorganisation of lipid rafts for signalling and/or intracellular transport in epithelial cells. T cell activation induces a rapid compartmentalisation of signalling machinery into reorganised rafts that are used as platforms for the assembly of the signalling complex. Costimulatory molecules participate in this process by providing signals that mobilise raft lipids and proteins, and remodel the cytoskeleton to the contact site. As in epithelial cells, rafts are used also as vesicular carriers for membrane trafficking in T lymphocytes. Furthermore, there are potential similarities between the specialised protein machinery underlying raft-mediated processes in T lymphocytes and polarised epithelial cells.

scholarly journals Sequential expression of genes involved in human T lymphocyte growth and differentiation.

1985 ◽  
Vol 161 (6) ◽  
pp. 1593-1598 ◽  
Author(s):  
M Krönke ◽  
W J Leonard ◽  
J M Depper ◽  
W C Greene
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Transferrin Receptor ◽  
Transcriptional Activity ◽  
Cell Activation ◽  
Receptor Gene ◽  
Ifn Gamma ◽  
Transient Event ◽  
Genes Encoding ◽  
Kinetics Of

Nuclear transcription assays were performed with isolated nuclei from human peripheral blood T lymphocytes stimulated with phytohemagglutinin and phorbol myristate acetate to determine the kinetics of transcriptional activity of various genes occurring in T cell activation. Although silent in resting T cells, the genes encoding c-myc and the interleukin 2 (IL-2) receptor were induced early, preceding gamma interferon (IFN-gamma), IL-2, and transferrin receptor gene transcription. Transcriptional activity of these genes fell after their respective peaks, indicating that the expression of these genes is a transient event during T cell activation. With the exception of the transferrin receptor gene, the kinetics of induction of these genes were not altered by concentrations of cycloheximide that inhibited protein synthesis. These data indicate that the induction of genes encoding c-myc, IL-2, IL-2 receptor, and IFN-gamma occur independently of the sequential production of the proteins they encode.

scholarly journals The role of β2 integrin in dendritic cell migration during infection

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tarfa Altorki ◽  
Werner Muller ◽  
Andrew Brass ◽  
Sheena Cruickshank
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
T Cell Activation ◽  
Cell Activation ◽  
Leukocyte Adhesion ◽  
Trichuris Muris ◽  
Dendritic Cell Migration ◽  
And Function ◽  
Kinetics Of

Abstract Background Dendritic cells (DCs) play a key role in shaping T cell responses. To do this, DCs must be able to migrate to the site of the infection and the lymph nodes to prime T cells and initiate the appropriate immune response. Integrins such as β2 integrin play a key role in leukocyte adhesion, migration, and cell activation. However, the role of β2 integrin in DC migration and function in the context of infection-induced inflammation in the gut is not well understood. This study looked at the role of β2 integrin in DC migration and function during infection with the nematode worm Trichuris muris. Itgb2tm1Bay mice lacking functional β2 integrin and WT littermate controls were infected with T. muris and the response to infection and kinetics of the DC response was assessed. Results In infection, the lack of functional β2 integrin significantly reduced DC migration to the site of infection but not the lymph nodes. The lack of functional β2 integrin did not negatively impact T cell activation in response to T. muris infection. Conclusions This data suggests that β2 integrins are important in DC recruitment to the infection site potentially impacting the initiation of innate immunity but is dispensible for DC migration to lymph nodes and T cell priming in the context of T. muris infection.

CD4+ T-cell activation impairs serogroup C Neisseria meningitis vaccine response in HIV-infected children

AIDS ◽  
2013 ◽  
Vol 27 (17) ◽  
pp. 2697-2705 ◽  
Author(s):  
Lucimar G. Milagres ◽  
Priscilla R. Costa ◽  
Bianca A.N. Santos ◽  
Giselle P. Silva ◽  
Aline C. Cruz ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Vaccine Response

scholarly journals Microclusters as T Cell Signaling Hubs: Structure, Kinetics, and Regulation

2021 ◽  
Vol 8 ◽  
Author(s):  
Lakshmi Balagopalan ◽  
Kumarkrishna Raychaudhuri ◽  
Lawrence E. Samelson
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Activation ◽  
Cell Activation ◽  
Vesicular Trafficking ◽  
Image Resolution ◽  
Live Cells ◽  
Cell Surface Signaling ◽  
Kinetics Of

When T cell receptors (TCRs) engage with stimulatory ligands, one of the first microscopically visible events is the formation of microclusters at the site of T cell activation. Since the discovery of these structures almost 20 years ago, they have been studied extensively in live cells using confocal and total internal reflection fluorescence (TIRF) microscopy. However, due to limits in image resolution and acquisition speed, the spatial relationships of signaling components within microclusters, the kinetics of their assembly and disassembly, and the role of vesicular trafficking in microcluster formation and maintenance were not finely characterized. In this review, we will summarize how new microscopy techniques have revealed novel insights into the assembly of these structures. The sub-diffraction organization of microclusters as well as the finely dissected kinetics of recruitment and disassociation of molecules from microclusters will be discussed. The role of cell surface molecules in microcluster formation and the kinetics of molecular recruitment via intracellular vesicular trafficking to microclusters is described. Finally, the role of post-translational modifications such as ubiquitination in the downregulation of cell surface signaling molecules is also discussed. These results will be related to the role of these structures and processes in T cell activation.

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