Evidence map›Paper›PMID 23382885›Full record

ArticlePloS one2013

Blockade of Kv1.3 potassium channels inhibits differentiation and granzyme B secretion of human CD8+ T effector memory lymphocytes.

Lina Hu, Tongguang Wang, Anne R Gocke, Avindra Nath, Hao Zhang, Joseph B Margolick, Katharine A Whartenby, Peter A Calabresi

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

24 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Inhibition of KCancers · 2024
    Article
  3. Activity of Potassium Channels in CD8International journal of molecular sciences · 2024
    Article
  4. Review
  5. Ionic Regulation of T-Cell Function and Anti-Tumour Immunity.International journal of molecular sciences · 2021
    Review
  6. Immunological Responses to Envenomation.Frontiers in immunology · 2021
    Review
  7. Article
  8. Review
  9. Review
  10. Altered CaInternational journal of molecular sciences · 2020
    Review
  11. Article
  12. PD1 blockade enhances KJournal for immunotherapy of cancer · 2020
    Article
  13. KCell communication and signaling : CCS · 2018
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Rational design of a Kv1.3 channel-blocking antibody as a selective immunosuppressant.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  19. Article
  20. 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

8 authors at 3 institutions in 1 country.

Lina HuDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Tongguang Wang
Anne R Gocke
Avindra Nath
Hao Zhang
Joseph B Margolick
Katharine A Whartenby
Peter A Calabresi
Johns Hopkins University · USJohns Hopkins Medicine · USNational Institutes of Health · US

Funding

Neuropathogenesis of Retroviral InfectionsZIANS003130 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI NATH, AVINDRA · 2011 to 2025
$73.7M
Study the pathogenesis of neurological disorders using human neural cultures derived from patient peripheral blood CD34 cellsZIANS003134 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI NATH, AVINDRA · 2012 to 2021
$11.3M
The Role of KV1.3 in Effector T cellsR01NS041435 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI CALABRESI, PETER A · 2000 to 2025
$5.8M
Mechanisms by which effector T cells modulate endogenous remyelinationR37NS041435 · NINDS · JOHNS HOPKINS UNIVERSITY · PI CALABRESI, PETER A · 2013 to 2019
$3.0M
NINDS NIH HHS NS041435NINDS NIH HHS R01 NS041435NINDS NIH HHS R37 NS041435
6 · The paper itself

Abstract

Increased expression of the voltage-gated potassium channel Kν1.3 on activated effector memory T cells (T(EM)) is associated with pathology in multiple sclerosis (MS). To date, most studies of Kν1.3 channels in MS have focused on CD4+ T(EM) cells. Much less is known about the functional relevance of Kv1.3 on CD8+ T(EM) cells. Herein, we examined the effects of Kν1.3 blockade on CD8+ T cell proliferation, differentiation into cytotoxic effector cells, and release of granzyme B (GrB), a key effector of CD8+ T cell-mediated cytotoxicity. We confirmed the expression of Kv1.3 channels on activated human CD8+ T lymphocytes by immunofluorescent staining. To test the functional relevance of the Kv1.3 channel in CD8+ T cells, we inhibited this channel via pharmacological blockers or a lentiviral-dominant negative (Kv1.xDN) approach and determined the effects of the blockade on critical pathogenic parameters of CD8+ T cells. We found that blockade of Kv1.3 with both lentivirus and pharmacologic agents effectively inhibited cytotoxic effector memory cells' proliferation, secretion of GrB, and their ability to kill neural progenitor cells. Intriguingly, the KvDN transduced T cells exhibited arrested differentiation from central memory (T(CM)) to effector memory (T(EM)) states. Transduction of cells that had already differentiated into T(EM) with KvDN led to their conversion into T(CM). CD8+ T(EM) have a critical role in MS and other autoimmune diseases. Our present results indicate a critical role for Kv1.3 in the conversion of CD8+ T cells into potential pathogenic effector cells with cytotoxic function.

Indexed as

CD8-Positive T-LymphocytesCell DifferentiationCell ProliferationGranzymesHumansImmunologic MemoryKv1.3 Potassium ChannelLymphocyte ActivationPotassium Channel BlockersGranzymesKv1.3 Potassium ChannelPotassium Channel Blockers

Identifiers

PMID23382885
PMCPMC3559683
OpenAlexW2001837924

What OpenQuestion holds

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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.