Evidence map›Paper›PMID 27526200›Full record

ArticlePloS one2016

Calcium Dynamics of Ex Vivo Long-Term Cultured CD8+ T Cells Are Regulated by Changes in Redox Metabolism.

Catherine A Rivet, Ariel S Kniss-James, Margaret A Gran, Anish Potnis, Abby Hill, Hang Lu, Melissa L Kemp

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 41% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Catherine A RivetSchool of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
Ariel S Kniss-JamesThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States of America.
Margaret A GranThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States of America.
Anish PotnisThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States of America.
Abby HillThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States of America.
Hang LuThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States of America.
Melissa L KempThe Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States of America.ORCID http://orcid.org/0000-0003-3781-8802
Georgia Institute of Technology · US

Funding

Redox regulation of cellular information processingDP2OD006483 · OD · GEORGIA INSTITUTE OF TECHNOLOGY · PI KEMP, MELISSA LAMBETH · 2009 to 2009
$2.3M
Spatiotemporal control of reactive oxygen species in T cellsR01AI088023 · NIAID · GEORGIA INSTITUTE OF TECHNOLOGY · PI KEMP, MELISSA LAMBETH · 2011 to 2014
$1.4M
A Computational Biology and Predictive Health Genomics Training Program at GTT32GM105490 · NIGMS · GEORGIA INSTITUTE OF TECHNOLOGY · PI GIBSON, GREGORY C · 2014 to 2018
$901k
Spatiotemporal control of reactive oxygen species in T cellsR56AI088023 · NIAID · GEORGIA INSTITUTE OF TECHNOLOGY · PI KEMP, MELISSA LAMBETH, LU, HANG · 2015 to 2015
$371k
NIAID NIH HHS R01 AI088023NIGMS NIH HHS T32 GM105490NIH HHS DP2 OD006483
6 · The paper itself

Abstract

T cells reach a state of replicative senescence characterized by a decreased ability to proliferate and respond to foreign antigens. Calcium release associated with TCR engagement is widely used as a surrogate measure of T cell response. Using an ex vivo culture model that partially replicates features of organismal aging, we observe that while the amplitude of Ca2+ signaling does not change with time in culture, older T cells exhibit faster Ca2+ rise and a faster decay. Gene expression analysis of Ca2+ channels and pumps expressed in T cells by RT-qPCR identified overexpression of the plasma membrane CRAC channel subunit ORAI1 and PMCA in older T cells. To test whether overexpression of the plasma membrane Ca2+ channel is sufficient to explain the kinetic information, we adapted a previously published computational model by Maurya and Subramaniam to include additional details on the store-operated calcium entry (SOCE) process to recapitulate Ca2+ dynamics after T cell receptor stimulation. Simulations demonstrated that upregulation of ORAI1 and PMCA channels is not sufficient to explain the observed alterations in Ca2+ signaling. Instead, modeling analysis identified kinetic parameters associated with the IP3R and STIM1 channels as potential causes for alterations in Ca2+ dynamics associated with the long term ex vivo culturing protocol. Due to these proteins having known cysteine residues susceptible to oxidation, we subsequently investigated and observed transcriptional remodeling of metabolic enzymes, a shift to more oxidized redox couples, and post-translational thiol oxidation of STIM1. The model-directed findings from this study highlight changes in the cellular redox environment that may ultimately lead to altered T cell calcium dynamics during immunosenescence or organismal aging.

Indexed as

AdultAgingBiological TransportCalciumCalcium SignalingCD8-Positive T-LymphocytesCell MembraneCytoplasmGene Expression RegulationHumansJurkat CellsModels, BiologicalOxidation-ReductionProtein Processing, Post-TranslationalRNA, MessengerStromal Interaction Molecule 1CalciumRNA, MessengerStromal Interaction Molecule 1Sulfhydryl Compounds

Identifiers

PMID27526200
PMCPMC4985122
OpenAlexW2514134211

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.