Evidence map›Paper›PMID 31219804›Full record

ArticleThe Journal of clinical investigation2019

Bystander responses impact accurate detection of murine and human antigen-specific CD8 T cells.

Matthew D Martin, Isaac J Jensen, Andrew S Ishizuka, Mitchell Lefebvre, Qiang Shan, Hai-Hui Xue, John T Harty, Robert A Seder, Vladimir P Badovinac

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

25 citing papers in PubMed, 30 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Review
  5. Antigen-specific TScience advances · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. IL-15-induced CD38Clinical & translational immunology · 2024
    Article
  13. Article
  14. Review
  15. Review
  16. Convergent clonal selection of donor- and recipient-derived CMV-specific T cells in hematopoietic stem cell transplant patients.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  17. Article
  18. Article
  19. Observational
  20. Article
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

9 authors at 2 institutions in 1 country.

Matthew D MartinDepartment of Pathology and.
Isaac J JensenInterdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USA.
Andrew S IshizukaVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Mitchell LefebvreInterdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USA.
Qiang ShanDepartment of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.
Hai-Hui XueInterdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, USA.
John T HartyDepartment of Pathology and.
Robert A SederVaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Vladimir P BadovinacDepartment of Pathology and.
University of Iowa · USNational Institute of Allergy and Infectious Diseases · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007171 · NIGMS · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 1985 to 2021
$31.2M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007337 · NIGMS · UNIVERSITY OF IOWA · PI GEYER, PAMELA K., LENTZ, STEVEN R · 1985 to 2020
$15.9M
TRAINING IN MECHANISMS OF PARASITISMT32AI007511 · NIAID · UNIVERSITY OF IOWA · PI BUTLER, NOAH SULLIVAN, WEBER, MARY · 1996 to 2025
$8.1M
INTERDISCIPLINARY IMMUNOLOGY TRAINING PROGRAMT32AI007260 · NIAID · UNIVERSITY OF IOWA · PI BUTLER, NOAH SULLIVAN, WU, LI · 1986 to 2023
$5.7M
PREDOCTORAL TRAINING PROGRAM IN IMMUNOLOGYT32AI007485 · NIAID · UNIVERSITY OF IOWA · PI Kevin L Legge · 1995 to 2026
$5.4M
Regulation of primary and secondary CD4 and CD8 T cell memoryR37AI042767 · NIAID · UNIVERSITY OF IOWA · PI HARTY, JOHN T · 2008 to 2017
$4.7M
Memory CD8 T cell localization and protection from influenzaR01AI114543 · NIAID · UNIVERSITY OF IOWA · PI BADOVINAC, VLADIMIR P, HARTY, JOHN T · 2015 to 2024
$4.4M
T resident memory in the lungR01AI042767 · NIAID · UNIVERSITY OF IOWA · PI HARTY, JOHN T · 1998 to 2023
$4.4M
Memory CD8 T cell immunity to Plasmodium liver stage infecR01AI085515 · NIAID · UNIVERSITY OF IOWA · PI HARTY, JOHN T · 2010 to 2020
$4.1M
Understanding immune regulation in blood-stage malariaR01AI100527 · NIAID · UNIVERSITY OF IOWA · PI HARTY, JOHN T · 2012 to 2021
$3.6M
Ezh2 regulates follicular helper T cell differentiationR01AI139874 · NIAID · UNIVERSITY OF IOWA · PI PENG, WEIQUN, XUE, HAI-HUI · 2018 to 2022
$2.4M
Impairment and recovery of CD8 T cell responses after sepsisR01GM113961 · NIGMS · UNIVERSITY OF IOWA · PI BADOVINAC, VLADIMIR P · 2015 to 2018
$1.2M
BLRD VA I01 BX002903NIAID NIH HHS R01 AI042767NIAID NIH HHS R01 AI085515NIAID NIH HHS R01 AI100527NIAID NIH HHS R01 AI114543NIAID NIH HHS R01 AI139874NIAID NIH HHS R21 AI042767NIAID NIH HHS R37 AI042767NIAID NIH HHS T32 AI007260NIAID NIH HHS T32 AI007485NIAID NIH HHS T32 AI007511NIGMS NIH HHS R01 GM113961NIGMS NIH HHS T32 GM007171NIGMS NIH HHS T32 GM007337NIH HHS S10 OD016199
6 · The paper itself

Abstract

Induction of memory CD8 T cells is important for controlling infections such as malaria HIV/AIDS, and for cancer immunotherapy. Accurate assessment of antigen (Ag)-specific CD8 T-cells is critical for vaccine optimization and defining correlates of protection. However, conditions for determining Ag-specific CD8 T-cell responses ex-vivo using ICS may be variable, especially in humans with complex antigens. Here, we used an attenuated whole parasite malaria vaccine model in humans and various experimental infections in mice to show that the duration of antigenic stimulation and timing of brefeldin A (BFA) addition influences the magnitude of Ag-specific and bystander T cell responses. Indeed, following immunization with an attenuated whole sporozoite malaria vaccine in humans, significantly higher numbers of IFN-γ producing memory CD8 T-cells comprised of antigen specific and bystander responses were detected by increasing the duration of Ag-stimulation prior to addition of BFA. Mechanistic analyses of virus-specific CD8 T-cells in mice revealed that the increase in IFNg producing CD8 T-cells was due to bystander activation of Ag-experienced memory CD8 T-cells, and correlated with the proportion of Ag-experienced CD8 T-cells in the stimulated populations. Incubation with anti-cytokine antibodies (ex. IL-12) improved accuracy in detecting bona-fide memory CD8 T-cell responses suggesting this as the mechanism for the bystander activation. These data have important implications for accurate assessment of immune responses generated by vaccines intended to elicit protective memory CD8 T-cells.

Indexed as

Bystander EffectAnimalsAntigensBrefeldin ACD8-Positive T-LymphocytesCytokinesFemaleHumansImmunizationImmunologic MemoryInterferon-gammaLeukocytes, MononuclearMalariaMalaria VaccinesMiceMice, Inbred C57BLAntigensBrefeldin ACytokinesInterferon-gammaMalaria VaccinesVaccines, AttenuatedAdaptive immunityImmunologyMemoryT cells

Identifiers

PMID31219804
PMCPMC6715387
OpenAlexW2950798083

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.