Evidence map›Paper›PMID 19783989›Full record

ArticleNature immunology2009

Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal.

Brian T Fife, Kristen E Pauken, Todd N Eagar, Takashi Obu, Jenny Wu, Qizhi Tang, Miyuki Azuma, Matthew F Krummel, Jeffrey A Bluestone

Open access · greenAbstract read
In one paragraph

Article in Nature immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 448 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
448citing papers in PubMed, 3 pooled it
11.2field-weighted citation impact, top 1% 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

448 citing papers in PubMed, 3 syntheses or guidelines pooled it, 736 citations in OpenAlex.

  1. Contribution of TLR4 to colorectal tumor microenvironment, etiology and prognosis.Journal of cancer research and clinical oncology · 2023
    Pooled it
  2. Pooled it
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  4. Article
  5. Review
  6. Article
  7. Article
  8. Programmed death-ligand 1 on ex vivo-expanded toll-like-receptor-Bregs prevents allograft rejection by Breg viability promotion, CD4American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026
    Article
  9. Article
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  12. Article
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  15. Review
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  19. PD-1 expressing islet-specific CD4Immunology and cell biology · 2025
    Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Brian T FifeUCSF Diabetes Center, Department of Medicine, University of California, San Francisco, California, USA. bfife@umn.edu
Kristen E Pauken
Todd N Eagar
Takashi Obu
Jenny Wu
Qizhi Tang
Miyuki Azuma
Matthew F Krummel
Jeffrey A Bluestone
University of California, San Francisco · USUniversity of Minnesota · USTokyo Medical and Dental University · JP

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2003 to 2019
$21.8M
Src tyrosine kinases and autoimmunity.P01AI035297 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ABBAS, ABUL K. · 1993 to 2010
$16.5M
NIAID NIH HHS AI35297NIAID NIH HHS P01 AI035297NIDDK NIH HHS P30 DK063720NIDDK NIH HHS P30 DK63720
6 · The paper itself

Abstract

Programmed death 1 (PD-1) is an inhibitory molecule expressed on activated T cells; however, the biological context in which PD-1 controls T cell tolerance remains unclear. Using two-photon laser-scanning microscopy, we show here that unlike naive or activated islet antigen-specific T cells, tolerized islet antigen-specific T cells moved freely and did not swarm around antigen-bearing dendritic cells (DCs) in pancreatic lymph nodes. Inhibition of T cell antigen receptor (TCR)-driven stop signals depended on continued interactions between PD-1 and its ligand, PD-L1, as antibody blockade of PD-1 or PD-L1 resulted in lower T cell motility, enhanced T cell-DC contacts and caused autoimmune diabetes. Blockade of the immunomodulatory receptor CTLA-4 did not alter T cell motility or abrogate tolerance. Thus, PD-1-PD-L1 interactions maintain peripheral tolerance by mechanisms fundamentally distinct from those of CTLA-4.

Indexed as

Immune ToleranceAnimalsAntigens, CDAntigens, SurfaceApoptosis Regulatory ProteinsB7-1 AntigenB7-H1 AntigenCell MovementCTLA-4 AntigenDendritic CellsDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Islets of LangerhansIslets of Langerhans TransplantationLymphocyte ActivationMembrane GlycoproteinsAntigens, CDAntigens, SurfaceApoptosis Regulatory ProteinsB7-1 AntigenB7-H1 AntigenCd274 protein, mouseCTLA-4 AntigenCtla4 protein, mouseMembrane GlycoproteinsPdcd1 protein, mousePeptidesProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-Cell

Identifiers

PMID19783989
PMCPMC2778301
OpenAlexW2108604103

What OpenQuestion holds

Textmetadata
LicenceTDM
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.