Evidence map›Paper›PMID 25803478›Full record

Trial reportPLoS pathogens2015

Human CD8+ T-cells recognizing peptides from Mycobacterium tuberculosis (Mtb) presented by HLA-E have an unorthodox Th2-like, multifunctional, Mtb inhibitory phenotype and represent a novel human T-cell subset.

Krista E van Meijgaarden, Mariëlle C Haks, Nadia Caccamo, Francesco Dieli, Tom H M Ottenhoff, Simone A Joosten

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 1 pooled it
9.1field-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

78 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. A cytoplasmic motif in HLA-E that drives clathrin-mediated endocytosis and VCP-associated postendocytic trafficking.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Vaccines · 2024
    Article
  13. bioRxiv : the preprint server for biology · 2024
    Article
  14. An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. iScience · 2024
    Article
  16. Review
  17. HLA-E/Frontiers in immunology · 2024
    Article
  18. MHC class Ib-restricted CD8Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  19. Article
  20. Intracellular trafficking of HLA-E and its regulation.The Journal of experimental medicine · 2023
    Article

18 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

6 authors at 2 institutions in 2 countries.

Krista E van MeijgaardenDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Mariëlle C HaksDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Nadia CaccamoCentral Laboratory for Advanced Diagnostic and Biomedical Research (CLADIBIOR), Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy.
Francesco DieliCentral Laboratory for Advanced Diagnostic and Biomedical Research (CLADIBIOR), Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy.
Tom H M OttenhoffDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Simone A JoostenDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Leiden University Medical Center · NLUniversity of Palermo · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mycobacterial antigens are not exclusively presented to T-cells by classical HLA-class Ia and HLA-class II molecules, but also through alternative antigen presentation molecules such as CD1a/b/c, MR1 and HLA-E. We recently described mycobacterial peptides that are presented in HLA-E and recognized by CD8+ T-cells. Using T-cell cloning, phenotyping, microbiological, functional and RNA-expression analyses, we report here that these T-cells can exert cytolytic or suppressive functions, inhibit mycobacterial growth, yet express GATA3, produce Th2 cytokines (IL-4,-5,-10,-13) and activate B-cells via IL-4. In TB patients, Mtb specific cells were detectable by peptide-HLA-E tetramers, and IL-4 and IL-13 were produced following peptide stimulation. These results identify a novel human T-cell subset with an unorthodox, multifunctional Th2 like phenotype and cytolytic or regulatory capacities, which is involved in the human immune response to mycobacteria and demonstrable in active TB patients' blood. The results challenge the current dogma that only Th1 cells are able to inhibit Mtb growth and clearly show that Th2 like cells can strongly inhibit outgrowth of Mtb from human macrophages. These insights significantly expand our understanding of the immune response in infectious disease.

Indexed as

Antigen PresentationBacterial ProteinsCD8-Positive T-LymphocytesCytokinesFemaleGATA3 Transcription FactorHistocompatibility Antigens Class IHLA-E AntigensHumansMacrophagesMaleMycobacterium tuberculosisPeptidesTh2 CellsBacterial ProteinsCytokinesGATA3 protein, humanGATA3 Transcription FactorHistocompatibility Antigens Class IHLA-E AntigensPeptides

Identifiers

PMID25803478
PMCPMC4372528
OpenAlexW2005670070

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Registered trials

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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.