Evidence map›Paper›PMID 33914024›Full record

ArticleThe Journal of experimental medicine2021

Altered selection on a single self-ligand promotes susceptibility to organ-specific T cell infiltration.

David E J Klawon, Dana C Gilmore, John D Leonard, Christine H Miller, Jaime L Chao, Matthew T Walker, Ryan K Duncombe, Kenneth S Tung, Erin J Adams, Peter A Savage

Open access · greenAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 37% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Tracking the role of Aire in immune tolerance to the eye with a TCR transgenic mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  3. Article
  4. Antigen-specific depletion of CD4Science immunology · 2022
    Article
  5. Review
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

10 authors at 2 institutions in 1 country.

David E J Klawon *Department of Pathology, University of Chicago, Chicago, IL.
Dana C Gilmore *Department of Pathology, University of Chicago, Chicago, IL.
John D LeonardDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL.
Christine H MillerDepartment of Pathology, University of Chicago, Chicago, IL.
Jaime L ChaoDepartment of Pathology, University of Chicago, Chicago, IL.
Matthew T WalkerDepartment of Pathology, University of Chicago, Chicago, IL.
Ryan K DuncombeDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL.
Kenneth S TungDepartment of Pathology, University of Virginia, Charlottesville, VA.
Erin J AdamsDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL.
Peter A SavageDepartment of Pathology, University of Chicago, Chicago, IL.
University of Chicago · USUniversity of Virginia · US

Funding

MEDICAL SCIENTIST TRAININGT32GM007281 · NIGMS · UNIVERSITY OF CHICAGO · PI CLARK, MARCUS RAMSAY · 1985 to 2022
$32.1M
INTERDISCIPLINARY TRAINING PROGRAM IN IMMUNOLOGYT32AI007090 · NIAID · UNIVERSITY OF CHICAGO · PI Peter Aidan Savage · 1985 to 2026
$11.7M
Multi-Disciplinary Training Grant in Cancer ResearchT32CA009594 · NCI · UNIVERSITY OF CHICAGO · PI KAY F MACLEOD, Scott A. Oakes · 1989 to 2026
$11.5M
Biochemical and cellular analysis of regulatory T cells reactive to a natural self antigenR01AI126756 · NIAID · UNIVERSITY OF CHICAGO · PI ADAMS, ERIN JUNE, SAVAGE, PETER AIDAN · 2016 to 2020
$3.3M
Specificity and function of memory-phenotype CD8+ T cells in the tumor environmentF30CA236061 · NCI · UNIVERSITY OF CHICAGO · PI MILLER, CHRISTINE · 2019 to 2022
$203k
NCI NIH HHS F30 CA236061NCI NIH HHS T32 CA009594NIAID NIH HHS R01 AI126756NIAID NIH HHS T32 AI007090NIGMS NIH HHS T32 GM007281
6 · The paper itself

Abstract

For the large array of self-peptide/MHC class II (pMHC-II) complexes displayed in the body, it is unclear whether CD4+ T cell tolerance must be imparted for each individual complex or whether pMHC-II-nonspecific bystander mechanisms are sufficient to confer tolerance by acting broadly on T cells reactive to multiple self-pMHC-II ligands. Here, via reconstitution of T cell-deficient mice, we demonstrate that altered T cell selection on a single prostate-specific self-pMHC-II ligand renders recipient mice susceptible to prostate-specific T cell infiltration. Mechanistically, this self-pMHC-II complex is required for directing antigen-specific cells into the Foxp3+ regulatory T cell lineage but does not induce clonal deletion to a measurable extent. Thus, our data demonstrate that polyclonal T reg cells are unable to functionally compensate for a breach in tolerance to a single self-pMHC-II complex in this setting, revealing vulnerabilities in antigen-nonspecific bystander mechanisms of immune tolerance.

Indexed as

AnimalsAntigensCD4-Positive T-LymphocytesCell LineDendritic CellsHistocompatibility Antigens Class IIImmune ToleranceInsectaLigandsLymphocyte ActivationMaleMiceMice, Inbred C57BLPeptidesT-Lymphocytes, RegulatoryAntigensHistocompatibility Antigens Class IILigandsPeptides

Identifiers

PMID33914024
PMCPMC8091134
OpenAlexW3157374765

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.