Evidence map›Paper›PMID 29857928›Full record

ArticleJournal of autoimmunity2018

Engineered MBP-specific human Tregs ameliorate MOG-induced EAE through IL-2-triggered inhibition of effector T cells.

Yong Chan Kim, Ai-Hong Zhang, Jeongheon Yoon, William E Culp, Jason R Lees, Kai W Wucherpfennig, David W Scott

Open access · greenAbstract read
In one paragraph

Article in Journal of autoimmunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

73 citing papers in PubMed, 113 citations in OpenAlex.

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  10. 3-in-oneiScience · 2025
    Article
  11. Local control of T cell fate in lymph nodes safely and durably reverses myelin-driven autoimmunity.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  12. Regulatory T Cell-Based Adoptive Cell Therapy in Autoimmunity.International journal of molecular sciences · 2025
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  17. CD4PeerJ · 2025
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13 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

7 authors at 2 institutions in 1 country.

Yong Chan KimDepartment of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Ai-Hong ZhangDepartment of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Jeongheon YoonDepartment of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
William E CulpOffice of Research, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Jason R LeesDepartment of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Kai W WucherpfennigDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
David W ScottDepartment of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. Electronic address: david.scott@usuhs.edu.
Uniformed Services University of the Health Sciences · USHarvard University · US

Funding

TCR recognition of MHC class II peptide compexes in multiple sclerosisP01AI045757 · NIAID · DANA-FARBER CANCER INSTITUTE · PI WUCHERPFENNIG, KAI W · 1999 to 2017
$22.8M
GENE THERAPEUTIC APPROACH FOR TOLERANCE INDUCTIONR01AI035622 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI SCOTT, DAVID WILLIAM · 1997 to 2013
$3.7M
Mechanisms of Tolerance Induction to FVIII in HemophiliaR56HL061883 · NHLBI · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI SCOTT, DAVID WILLIAM · 2014 to 2014
$380k
NHLBI NIH HHS R56 HL061883NIAID NIH HHS P01 AI045757NIAID NIH HHS R01 AI035622
6 · The paper itself

Abstract

Expanded polyclonal T regulatory cells (Tregs) offer great promise for the treatment of immune-mediated diseases. Inhibition by Tregs is under the control of the T-cell receptor (TCR). Therefore, we created Tregs with defined antigen specificity, using a recombinant T-cell receptor isolated from a myelin-basic protein specific T-cell clone of a multiple sclerosis (MS) patient (Ob2F3). We expressed this TCR using a retroviral expression vector in human Tregs from peripheral blood. We observed that transduced Tregs were activated in vitro in response to myelin basic protein (MBP) peptide on DR15 antigen-presenting cells (APC) and upregulated Treg markers, Foxp3, LAP and Helios. These engineered MBP-specific Tregs could suppress MBP-specific T effector cells, and were also able to suppress T cells with other specificities after Tregs had been activated through the TCR. Importantly, we showed that these engineered Tregs were able to function effectively in the presence of strong TLR-induced inflammatory signals, and that MBP-specific Tregs ameliorated EAE in myelin oligodendrocyte glycoprotein (MOG)-immunized DR15 transgenic mice. We further demonstrated in vitro that IL-2 produced by neighboring effector T cells activated MBP-specific Tregs, initiating contact-independent suppression to T effectors in local milieu. Mechanistic studies demonstrated that bystander suppression in vivo may involve transfer of soluble mediators, enhanced by cell contact between Tregs and effectors. Taken together, we show that engineered clonal MBP-specific Tregs are able to suppress autoimmune pathology in EAE. This approach may serve as a cellular therapy for MS patients with the common DR15 haplotype that is associated with disease susceptibility.

Indexed as

AnimalsAutoimmunityBystander EffectCells, CulturedDisease Models, AnimalEncephalomyelitis, Autoimmune, ExperimentalForkhead Transcription FactorsGenetic EngineeringGenetic Predisposition to DiseaseHLA-DR Serological SubtypesHumansImmunotherapy, AdoptiveInterleukin-2Lymphocyte ActivationMiceMice, TransgenicForkhead Transcription FactorsFOXP3 protein, humanHLA-DR15 antigenHLA-DR Serological SubtypesInterleukin-2Myelin Basic ProteinMyelin-Oligodendrocyte GlycoproteinReceptors, Antigen, T-Cell

Identifiers

PMID29857928
PMCPMC6054915
OpenAlexW2805549191

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.