Evidence map›Paper›PMID 22384114›Full record

ArticlePloS one2012

Cytotoxicity of CD56(bright) NK cells towards autologous activated CD4+ T cells is mediated through NKG2D, LFA-1 and TRAIL and dampened via CD94/NKG2A.

Natasja Nielsen, Niels Ødum, Birgitte Ursø, Lewis L Lanier, Pieter Spee

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.

0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

114 citing papers in PubMed, 169 citations in OpenAlex.

  1. Trial
  2. A CD8Nature communications · 2021
    Trial
  3. Trial
  4. Trial
  5. Unconventional functions of natural killer cells in homeostasis and disease.Journal of immunology (Baltimore, Md. : 1950) · 2026
    Review
  6. Article
  7. Article
  8. CD56Clinical & translational immunology · 2026
    Article
  9. Review
  10. Killing the killers: Natural killer cell therapy targeting glioma stem cells in high-grade glioma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Natural killer cells in multiple sclerosis: foe or friends?Frontiers in cellular neuroscience · 2025
    Review
  16. Article
  17. Single-cell profiling identifies a CD8Nature communications · 2024
    Article
  18. Generation of an Inhibitory NK Cell Subset by TGF-β1/IL-15 Polarization.Journal of immunology (Baltimore, Md. : 1950) · 2024
    Article
  19. Article
  20. Review

54 more citing papers are in PubMed but not listed here.

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

5 authors at 4 institutions in 2 countries.

Natasja NielsenTranslational Immunology, Novo Nordisk A/S, Måløv, Denmark.
Niels Ødum
Birgitte Ursø
Lewis L Lanier
Pieter Spee
Novo Nordisk (Denmark) · DKCancer Research Institute · USUniversity of California, San Francisco · USUniversity of Copenhagen · DK

Funding

NK and T Cell Costimulation by NKG2D/DAP10R37AI066897 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LANIER, LEWIS LEE · 2006 to 2015
$3.8M
NIAID NIH HHS AI066897NIAID NIH HHS R37 AI066897
6 · The paper itself

Abstract

In mouse models of chronic inflammatory diseases, Natural Killer (NK) cells can play an immunoregulatory role by eliminating chronically activated leukocytes. Indirect evidence suggests that NK cells may also be immunoregulatory in humans. Two subsets of human NK cells can be phenotypically distinguished as CD16(+)CD56(dim) and CD16(dim/-)CD56(bright). An expansion in the CD56(bright) NK cell subset has been associated with clinical responses to therapy in various autoimmune diseases, suggesting an immunoregulatory role for this subset in vivo. Here we compared the regulation of activated human CD4(+) T cells by CD56(dim) and CD56(bright) autologous NK cells in vitro. Both subsets efficiently killed activated, but not resting, CD4(+) T cells. The activating receptor NKG2D, as well as the integrin LFA-1 and the TRAIL pathway, played important roles in this process. Degranulation by NK cells towards activated CD4(+) T cells was enhanced by IL-2, IL-15, IL-12+IL-18 and IFN-α. Interestingly, IL-7 and IL-21 stimulated degranulation by CD56(bright) NK cells but not by CD56(dim) NK cells. NK cell killing of activated CD4(+) T cells was suppressed by HLA-E on CD4(+) T cells, as blocking the interaction between HLA-E and the inhibitory CD94/NKG2A NK cell receptor enhanced NK cell degranulation. This study provides new insight into CD56(dim) and CD56(bright) NK cell-mediated elimination of activated autologous CD4(+) T cells, which potentially may provide an opportunity for therapeutic treatment of chronic inflammation.

Indexed as

AnimalsCD4-Positive T-LymphocytesCD56 AntigenFlow CytometryHumansInflammationIntegrinsInterleukin-7Killer Cells, NaturalLeukocytes, MononuclearLymphocyte Function-Associated Antigen-1MiceModels, StatisticalNK Cell Lectin-Like Receptor Subfamily DNK Cell Lectin-Like Receptor Subfamily KTNF-Related Apoptosis-Inducing LigandCD56 AntigenIntegrinsInterleukin-7KLRK1 protein, humanLymphocyte Function-Associated Antigen-1NK Cell Lectin-Like Receptor Subfamily DNK Cell Lectin-Like Receptor Subfamily KTNF-Related Apoptosis-Inducing Ligand

Identifiers

PMID22384114
PMCPMC3284517
OpenAlexW1963676215

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.