Evidence map›Paper›PMID 23818845›Full record

Trial reportPLoS pathogens2013

Galectin-9 and IL-21 mediate cross-regulation between Th17 and Treg cells during acute hepatitis C.

Hassen Kared, Thomas Fabre, Nathalie Bédard, Julie Bruneau, Naglaa H Shoukry

Open access · goldAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
7.5field-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

87 citing papers in PubMed, 141 citations in OpenAlex.

  1. Trial
  2. Trial
  3. HCV-specific CD4EBioMedicine · 2026
    Article
  4. Review
  5. Hepatitis C virus modifiedJournal of virology · 2025
    Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Follicular helper-T cells restore CD8Journal for immunotherapy of cancer · 2021
    Article
  18. Review
  19. Review
  20. Review

27 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 2 institutions in 1 country.

Hassen KaredCentre de Recherche du Centre Hospitalier de l'Université de Montréal, Hôpital St-Luc, Montréal, Québec, Canada.
Thomas Fabre
Nathalie Bédard
Julie Bruneau
Naglaa H Shoukry
Centre Hospitalier de l’Université de Montréal · CAUniversité de Montréal · CA

Funding

International Collaborative of prospective studies of HIV and Hepatitis in IDUR01DA031056 · NIDA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI PAGE, KIMBERLY · 2011 to 2015
$2.2M
CIHR HEO-115696CIHR MOP-106468NIDA NIH HHS R01 DA031056NIDA NIH HHS R01DA031056
6 · The paper itself

Abstract

Loss of CD4 T cell help correlates with virus persistence during acute hepatitis C virus (HCV) infection, but the underlying mechanism(s) remain unknown. We developed a combined proliferation/intracellular cytokine staining assay to monitor expansion of HCV-specific CD4 T cells and helper cytokines expression patterns during acute infections with different outcomes. We demonstrate that acute resolving HCV is characterized by strong Th1/Th17 responses with specific expansion of IL-21-producing CD4 T cells and increased IL-21 levels in plasma. In contrast, viral persistence was associated with lower frequencies of IL-21-producing CD4 T cells, reduced proliferation and increased expression of the inhibitory receptors T cell immunoglobulin and mucin-domain-containing-molecule-3 (Tim-3), programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) on HCV-specific CD8 T cells. Progression to persistent infection was accompanied by increased plasma levels of the Tim-3 ligand Galectin-9 (Gal-9) and expansion of Gal-9 expressing regulatory T cells (Tregs). In vitro supplementation of Tim-3(high) HCV-specific CD8 T cells with IL-21 enhanced their proliferation and prevented Gal-9 induced apoptosis. siRNA-mediated knockdown of Gal-9 in Treg cells rescued IL-21 production by HCV-specific CD4 T cells. We propose that failure of CD4 T cell help during acute HCV is partially due to an imbalance between Th17 and Treg cells whereby exhaustion of both CD4 and CD8 T cells through the Tim-3/Gal-9 pathway may be limited by IL-21 producing Th17 cells or enhanced by Gal-9 producing Tregs.

Indexed as

Cell ProliferationAcute DiseaseCD8-Positive T-LymphocytesCells, CulturedFemaleFollow-Up StudiesGalectinsGene Expression RegulationHepatitis A Virus Cellular Receptor 2Hepatitis CHumansInterleukin-21InterleukinsMaleMembrane ProteinsProgrammed Cell Death 1 ReceptorGalectinsHAVCR2 protein, humanHepatitis A Virus Cellular Receptor 2Interleukin-21InterleukinsLGALS9 protein, humanMembrane ProteinsPDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID23818845
PMCPMC3688567
OpenAlexW2016081852

What OpenQuestion holds

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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.