Evidence map›Paper›PMID 19628705›Full record

ArticleBlood2009

Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors.

Yenan T Bryceson, Hans-Gustaf Ljunggren, Eric O Long

Open access · hybridAbstract read
In one paragraph

Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed, 1 pooled it
7.4field-weighted citation impact, top 2% 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

150 citing papers in PubMed, 1 synthesis or guideline pooled it, 268 citations in OpenAlex.

  1. Pooled it
  2. NK Cell Activity and CD57Frontiers in immunology · 2020
    Trial
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Cancer cells suppress NK cell activity by actin-driven polarization of inhibitory ligands to the immunological synapse.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

90 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

3 authors at 2 institutions in 2 countries.

Yenan T BrycesonLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, MD 20852, USA. yenan.bryceson@ki.se
Hans-Gustaf Ljunggren
Eric O Long
National Institute of Allergy and Infectious Diseases · USKarolinska University Hospital · SE

Funding

Regulation of innate lymphocyte functionZIAAI000525 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LONG, ERIC O · 2009 to 2024
$12.0M
MOLECULAR ANALYSIS OF HUMAN NATURAL KILLER CELLSZ01AI000525 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI LONG, ERIC O · 1988 to 2008
$4.7M
Intramural NIH HHS
6 · The paper itself

Abstract

Natural killer (NK) cells provide innate control of infected and neoplastic cells. Multiple receptors have been implicated in natural cytotoxicity, but their individual contribution remains unclear. Here, we studied the activation of primary, resting human NK cells by Drosophila cells expressing ligands for receptors NKG2D, DNAM-1, 2B4, CD2, and LFA-1. Each receptor was capable of inducing inside-out signals for LFA-1, promoting adhesion, but none induced degranulation. Rather, release of cytolytic granules required synergistic activation through coengagement of receptors, shown here for NKG2D and 2B4. Although engagement of NKG2D and 2B4 was not sufficient for strong target cell lysis, collective engagement of LFA-1, NKG2D, and 2B4 defined a minimal requirement for natural cytotoxicity. Remarkably, inside-out signaling induced by each one of these receptors, including LFA-1, was inhibited by receptor CD94/NKG2A binding to HLA-E. Strong inside-out signals induced by the combination of NKG2D and 2B4 or by CD16 could overcome CD94/NKG2A inhibition. In contrast, degranulation induced by these receptors was still subject to inhibition by CD94/NKG2A. These results reveal multiple layers in the activation pathway for natural cytotoxicity and that steps as distinct as inside-out signaling to LFA-1 and signals for granule release are sensitive to inhibition by CD94/NKG2A.

Indexed as

AnimalsAntigens, CDCell DegranulationCells, CulturedCytotoxicity, ImmunologicDrosophilaHumansK562 CellsKiller Cells, NaturalLymphocyte ActivationLymphocyte Function-Associated Antigen-1NK Cell Lectin-Like Receptor Subfamily DNK Cell Lectin-Like Receptor Subfamily KReceptors, ImmunologicReceptors, Natural Cytotoxicity TriggeringSignaling Lymphocytic Activation Molecule FamilyAntigens, CDCd244a protein, mouseKLRD1 protein, humanKLRK1 protein, humanLymphocyte Function-Associated Antigen-1NK Cell Lectin-Like Receptor Subfamily DNK Cell Lectin-Like Receptor Subfamily KReceptors, ImmunologicReceptors, Natural Cytotoxicity TriggeringSignaling Lymphocytic Activation Molecule Family

Identifiers

PMID19628705
PMCPMC2756125
OpenAlexW2013473454

What OpenQuestion holds

Textmetadata
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.