Evidence map›Paper›PMID 27500209›Full record

ArticleTransplantation direct2015

Detection of Virus-Specific CD8+ T Cells With Cross-Reactivity Against Alloantigens: Potency and Flaws of Present Experimental Methods.

Heleen van den Heuvel, Kirstin M Heutinck, Ellen P M W van der Meer-Prins, Si La Yong, Frans H J Claas, Ineke J M Ten Berge

Open access · goldAbstract read
In one paragraph

Article in Transplantation direct, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 30% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. Observational
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 1 country.

Heleen van den HeuvelDepartment of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Kirstin M HeutinckDepartment of Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands.; Renal Transplant Unit, Division of Internal Medicine, Department of Nephrology, Academic Medical Centre, Amsterdam, The Netherlands.
Ellen P M W van der Meer-PrinsDepartment of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Si La YongDepartment of Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands.; Renal Transplant Unit, Division of Internal Medicine, Department of Nephrology, Academic Medical Centre, Amsterdam, The Netherlands.
Frans H J ClaasDepartment of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Ineke J M Ten BergeRenal Transplant Unit, Division of Internal Medicine, Department of Nephrology, Academic Medical Centre, Amsterdam, The Netherlands.
Leiden University Medical Center · NLAcademic Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

unlabelledVirus-specific T cells have the intrinsic capacity to cross-react against allogeneic HLA antigens, a phenomenon known as heterologous immunity. In transplantation, these cells may contribute to the alloimmune response and negatively impact graft outcome. This study describes the various techniques that can be used to detect heterologous immune responses of virus-specific CD8(+) T cells against allogeneic HLA antigens. The strengths and weaknesses of the different approaches are discussed and illustrated by experimental data.

methodsMixed-lymphocyte reactions (MLRs) were performed to detect allo-HLA cross-reactivity of virus-specific CD8(+) T cells in total peripheral blood mononuclear cells. T-cell lines and clones were generated to confirm allo-HLA cross-reactivity by IFNγ production and cytotoxicity. In addition, the conventional MLR protocol was adjusted by introducing a 3-day resting phase and subsequent short restimulation with alloantigen or viral peptide, whereupon the expression of IFNγ, IL-2, CD107a, and CD137 was determined.

resultsThe accuracy of conventional MLR is challenged by potential bystander activation. T-cell lines and clones can circumvent this issue, yet their generation is laborious and time-consuming. Using the adjusted MLR and restimulation protocol, we found that only truly cross-reactive T cells responded to re-encounter of alloantigen and viral peptide, whereas bystander-activated cells did not.

conclusionsThe introduction of a restimulation phase improved the accuracy of the MLR as a screening tool for the detection of allo-HLA cross-reactivity by virus-specific CD8(+) T cells at bulk level. For detailed characterization of cross-reactive cells, T-cell lines and clones remain the golden standard.

Identifiers

PMID27500209
PMCPMC4946452
OpenAlexW2521025170

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.