Evidence map›Paper›PMID 23824823›Full record

ArticleJournal of virology2013

High production rates sustain in vivo levels of PD-1high simian immunodeficiency virus-specific CD8 T cells in the face of rapid clearance.

Constantinos Petrovas, Takuya Yamamoto, David A Price, Srinivas S Rao, Nichole R Klatt, Jason M Brenchley, Daniel C Douek, Emma Gostick, Bastian R Angermann, Zvi Grossman and 3 more

Abstract read
In one paragraph

Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Mechanisms of CD8European journal of immunology · 2018
    Review
  4. Article
  5. Solving Immunology?Trends in immunology · 2017
    Review
  6. Article
  7. 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

13 authors.

Constantinos PetrovasImmunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Takuya Yamamoto
David A Price
Srinivas S Rao
Nichole R Klatt
Jason M Brenchley
Daniel C Douek
Emma Gostick
Bastian R Angermann
Zvi Grossman
Derek C Macallan
Martin Meier-Schellersheim
Richard A Koup

Funding

Mechanisms of Immune Activation and Disease Progression in Animal ModelsZIAAI001029 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BRENCHLEY, JASON · 2009 to 2025
$28.2M
Computational Biology in Systems Immunology and Infectious Disease ModelingZIAAI001076 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MEIER-SCHELLERSHEIM, MARTIN · 2009 to 2025
$25.4M
Testing of Blood Samples for Immune Response and Vaccine ResearchZIAAI005073 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI KOUP, RICHARD A · 2009 to 2025
$23.4M
T Cell Immune Responses To HIV And Other PathogensZIAAI005033 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DOUEK, DANIEL CESAR · 2009 to 2025
$11.4M
The HIV ReservoirZIAAI005034 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DOUEK, DANIEL CESAR · 2009 to 2025
$7.5M
Mathematical Modeling of Cell Population DynamicsZIAAI001116 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MEIER-SCHELLERSHEIM, MARTIN · 2009 to 2017
$896k
Intramural NIH HHSMedical Research Council G0500628Medical Research Council G1001052Wellcome Trust 100326
6 · The paper itself

Abstract

Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced in vitro proliferation capacity. However, the cellular mechanisms that sustain PD-1(high) virus-specific CD8 T cell responses during chronic infection are unknown. Here, we show that the PD-1(high) phenotype is associated with accelerated in vivo CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIV-specific CD8 T cell pool. Mathematical modeling of 5-bromo-2' deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1(high) compared to PD-1(low) CD8 T cells in all memory compartments. Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex in vivo turnover profile whereby only a small fraction of PD-1(high) cells, but virtually all PD-1(low) cells, returned to rest after activation. Similar kinetics operated in both chronic and acute SIV infection. Our data suggest that the persistence of PD-1(high) SIV-specific CD8 T cells in chronic infection is maintained in vivo by a mechanism involving high production coupled with a high disappearance rate.

Indexed as

Acute DiseaseAnimalsCD8-Positive T-LymphocytesCell ProliferationChronic DiseaseCytokinesImmunologic MemoryLymphocyte ActivationMacaca mulattaProgrammed Cell Death 1 ReceptorResting Phase, Cell CycleSimian Acquired Immunodeficiency SyndromeSimian Immunodeficiency VirusT-Lymphocyte SubsetsCytokinesProgrammed Cell Death 1 Receptor

Identifiers

PMID23824823
PMCPMC3754085

What OpenQuestion holds

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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.