Evidence map›Paper›PMID 21965332›Full record

ArticleThe Journal of clinical investigation2011

A high-throughput single-cell analysis of human CD8⁺ T cell functions reveals discordance for cytokine secretion and cytolysis.

Navin Varadarajan, Boris Julg, Yvonne J Yamanaka, Huabiao Chen, Adebola O Ogunniyi, Elizabeth McAndrew, Lindsay C Porter, Alicja Piechocka-Trocha, Brenna J Hill, Daniel C Douek and 3 more

Open access · bronzeAbstract readEvaluation StudyValidation Study
In one paragraph

Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
6.8field-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

85 citing papers in PubMed, 155 citations in OpenAlex.

  1. Immunotherapy Targeting HPV16/18 Generates Potent Immune Responses in HPV-Associated Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
    Trial
  2. Article
  3. Review
  4. Article
  5. Article
  6. Heterogeneity in killing efficacy of individual effector CD8Proceedings. Biological sciences · 2023
    Article
  7. Article
  8. Article
  9. Article
  10. Microraft arrays for serial-killer CD19 chimeric antigen receptor T cells and single cell isolation.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2023
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. T cell and antibody functional correlates of severe COVID-19.medRxiv : the preprint server for health sciences · 2020
    Article
  17. Article
  18. CD8Nature reviews. Immunology · 2020
    Review
  19. Review
  20. Article

25 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

13 authors at 5 institutions in 1 country.

Navin VaradarajanDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Boris Julg
Yvonne J Yamanaka
Huabiao Chen
Adebola O Ogunniyi
Elizabeth McAndrew
Lindsay C Porter
Alicja Piechocka-Trocha
Brenna J Hill
Daniel C Douek
Florencia Pereyra
Bruce D Walker
J Christopher Love
Ragon Institute of MGH, MIT and Harvard · USHoward Hughes Medical Institute · USMassachusetts Institute of Technology · USNational Institute of Allergy and Infectious Diseases · USBroad Institute · US

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ROBERT A. PARKER · 2004 to 2026
$94.4M
Interdepartmental Biotechnology Training ProgramT32GM008334 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WITTRUP, KARL DANE · 1989 to 2018
$15.2M
PARTNERS/FENWAY/SHATTUCK CENTER FOR AIDS RESEARCHP30AI042851 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI WALKER, BRUCE D · 2000 to 2003
$5.7M
INHIBITION OF HIV1 REPLICATION BY CYTOTOXIC LYMPHOCYTESR01AI030914 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI WALKER, BRUCE D · 1991 to 2013
$4.2M
NIAID NIH HHS P30 AI042851NIAID NIH HHS P30 AI060354NIAID NIH HHS R01 AI030914NIGMS NIH HHS 5T32GM008334NIGMS NIH HHS T32 GM008334
6 · The paper itself

Abstract

CD8+ T cells are a key component of the adaptive immune response to viral infection. An inadequate CD8+ T cell response is thought to be partly responsible for the persistent chronic infection that arises following infection with HIV. It is therefore critical to identify ways to define what constitutes an adequate or inadequate response. IFN-γ production has been used as a measure of T cell function, but the relationship between cytokine production and the ability of a cell to lyse virus-infected cells is not clear. Moreover, the ability to assess multiple CD8+ T cell functions with single-cell resolution using freshly isolated blood samples, and subsequently to recover these cells for further functional analyses, has not been achieved. As described here, to address this need, we have developed a high-throughput, automated assay in 125-pl microwells to simultaneously evaluate the ability of thousands of individual CD8+ T cells from HIV-infected patients to mediate lysis and to produce cytokines. This concurrent, direct analysis enabled us to investigate the correlation between immediate cytotoxic activity and short-term cytokine secretion. The majority of in vivo primed, circulating HIV-specific CD8+ T cells were discordant for cytolysis and cytokine secretion, notably IFN-γ, when encountering cognate antigen presented on defined numbers of cells. Our approach should facilitate determination of signatures of functional variance among individual effector CD8+ T cells, including those from mucosal samples and those induced by vaccines.

Indexed as

Cytotoxicity, ImmunologicAdaptive ImmunityAntigen-Presenting CellsCD8-Positive T-LymphocytesCytokinesHigh-Throughput Screening AssaysHIV Core Protein p24HIV InfectionsHIV Long-Term SurvivorsHumansInterferon-gammaIn Vitro TechniquesSingle-Cell AnalysisT-Lymphocytes, CytotoxicCytokinesHIV Core Protein p24Interferon-gammap24 protein, Human Immunodeficiency Virus Type 1

Identifiers

PMID21965332
PMCPMC3204845
OpenAlexW2128416381

What OpenQuestion holds

Textmetadata
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.