Evidence map›Paper›PMID 32976527›Full record

ArticlePLoS pathogens2020

CX3CL1 and IL-15 Promote CD8 T cell chemoattraction in HIV and in atherosclerosis.

Soumya Panigrahi, Bonnie Chen, Mike Fang, Daria Potashnikova, Alexey A Komissarov, Anna Lebedeva, Gillian M Michaelson, Jonathan M Wyrick, Stephen R Morris, Scott F Sieg and 13 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 17% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. The CX3CL1-CX3CR1 axis in HIV-associated inflammation and cardiometabolic disease.American journal of physiology. Regulatory, integrative and comparative physiology · 2026
    Review
  4. Article
  5. CD8Nature reviews. Cardiology · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Infection and immunity · 2025
    Article
  10. Review
  11. Observational
  12. CX3CR1Cancer science · 2024
    Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Immunosenescence: an unexplored role in glomerulonephritis.Clinical & translational immunology · 2022
    Review
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

23 authors at 9 institutions in 2 countries.

Soumya PanigrahiCenter for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine/University Hospitals, Cleveland Medical Center, Cleveland, OH, United States of America.
Bonnie ChenCenter for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine/University Hospitals, Cleveland Medical Center, Cleveland, OH, United States of America.
Mike FangDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America.ORCID 0000-0002-8318-1016
Daria PotashnikovaLaboratory of Atherothrombosis, Moscow State University of Medicine and Dentistry, Moscow, Russia.ORCID 0000-0002-0098-827X
Alexey A KomissarovLaboratory of Atherothrombosis, Moscow State University of Medicine and Dentistry, Moscow, Russia.ORCID 0000-0003-1018-5195
Anna LebedevaLaboratory of Atherothrombosis, Moscow State University of Medicine and Dentistry, Moscow, Russia.
Gillian M MichaelsonCenter for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine/University Hospitals, Cleveland Medical Center, Cleveland, OH, United States of America.ORCID 0000-0003-1499-7721
Jonathan M WyrickCenter for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine/University Hospitals, Cleveland Medical Center, Cleveland, OH, United States of America.
Stephen R MorrisCleveland Louis Stokes Veterans Affairs Medical Center, Cleveland, OH, United States of America.
Scott F SiegCenter for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine/University Hospitals, Cleveland Medical Center, Cleveland, OH, United States of America.ORCID 0000-0002-1769-8682
Mirko PaiardiniDivision of Microbiology and Immunology, Yerkes National Primate Research Center, and Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, United States of America.
Francois J VillingerNew Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, United States of America.ORCID 0000-0002-7790-2008
Karem HarthHarrington Heart & Vascular Institute, University Hospitals, Cleveland Medical Center/Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America.
Vikram S KashyapHarrington Heart & Vascular Institute, University Hospitals, Cleveland Medical Center/Case Western Reserve University, School of Medicine, Cleveland, OH, United States of America.
Mark J CameronDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America.ORCID 0000-0003-4768-4094
Cheryl M CameronDepartment of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America.
Elena VasilievaLaboratory of Atherothrombosis, Moscow State University of Medicine and Dentistry, Moscow, Russia.
Leonid MargolisSection on Intercellular Interactions, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States of America.
Souheil-Antoine YounesCenter for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine/University Hospitals, Cleveland Medical Center, Cleveland, OH, United States of America.ORCID 0000-0003-2186-7140
Nicholas T FunderburgSchool of Health and Rehabilitation Sciences, Ohio State University, Columbus, OH, United States of America.ORCID 0000-0003-3113-1217
David A ZidarCleveland Louis Stokes Veterans Affairs Medical Center, Cleveland, OH, United States of America.
Michael M LedermanCenter for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine/University Hospitals, Cleveland Medical Center, Cleveland, OH, United States of America.ORCID 0000-0001-9247-8025
Michael L FreemanCenter for AIDS Research, Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine/University Hospitals, Cleveland Medical Center, Cleveland, OH, United States of America.ORCID 0000-0002-7690-5258
University Hospitals of Cleveland · USMoscow State University of Medicine and Dentistry · RUCase Western Reserve University · USEmory University · USLouis Stokes Cleveland VA Medical Center · USNational Institutes of Health · USThe Ohio State University · USUniversity of Louisiana at Lafayette · USUniversity School · US

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
WG3: HIV, Co-infections and Co-morbiditiesP30AI036219 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI Alan David Levine · 1994 to 2026
$50.0M
Case Clinical Trials Unit: Administrative Supplement NOSI AI-20-031.UM1AI069501 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI George Yendewa · 2012 to 2026
$40.4M
Viral Testing Core-Maintenance of the SPF Breeding Colonies at Yerkes National Primate Research CenterU42OD011023 · OD · EMORY UNIVERSITY · PI Matthew Ryan Gardner · 2018 to 2026
$17.5M
Case AIDS Clinical Trials UnitU01AI069501 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI LEDERMAN, MICHAEL MARCEL · 2007 to 2011
$14.7M
Clinical and Translational Science Collaborative of ClevelandKL2TR000440 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$11.1M
Specimen Acquisition and Distribution CoreP01AI076174 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI LANDAY, ALAN L · 2008 to 2012
$10.9M
Cellular mediators of vascular inflammation in treated HIV-infectionR01HL134544 · NHLBI · OHIO STATE UNIVERSITY · PI FUNDERBURG, NICHOLAS T. · 2016 to 2019
$3.2M
NCATS NIH HHS KL2 TR000440NHLBI NIH HHS R01 HL134544NIAID NIH HHS P01 AI076174NIAID NIH HHS P30 AI036219NIAID NIH HHS U01 AI069501NIAID NIH HHS UM1 AI069501NIH HHS P51 OD011132NIH HHS U42 OD011023
6 · The paper itself

Abstract

Atherosclerotic cardiovascular disease (ASCVD) remains an important cause of morbidity in the general population and risk for ASCVD is increased approximately 2-fold in persons living with HIV infection (PLWH). This risk is linked to elevated CD8 T cell counts that are abundant in atherosclerotic plaques and have been implicated in disease pathogenesis yet the mechanisms driving T cell recruitment to and activation within plaques are poorly defined. Here we investigated the role of CD8 T cells in atherosclerosis in a non-human primate model of HIV infection and in the HIV-uninfected elderly; we sought to identify factors that promote the activation, function, and recruitment to endothelium of CX3CR1+ CD8 T cells. We measured elevated expression of CX3CL1 and IL-15, and increased CD8 T cell numbers in the aortas of rhesus macaques infected with SIV or SHIV, and demonstrated similar findings in atherosclerotic vessels of HIV-uninfected humans. We found that recombinant TNF enhanced the production and release of CX3CL1 and bioactive IL-15 from aortic endothelial cells, but not from aortic smooth muscle cells. IL-15 in turn promoted CX3CR1 surface expression on and TNF synthesis by CD8 T cells, and IL-15-treated CD8 T cells exhibited enhanced CX3CL1-dependent chemoattraction toward endothelial cells in vitro. Finally, we show that CD8 T cells in human atherosclerotic plaques have an activated, resident phenotype consistent with in vivo IL-15 and CX3CL1 exposure. In this report, we define a novel model of CD8 T cell involvement in atherosclerosis whereby CX3CL1 and IL-15 operate in tandem within the vascular endothelium to promote infiltration by activated CX3CR1+ memory CD8 T cells that drive further endothelial activation via TNF. We propose that these interactions are prevalent in aging and in PLWH, populations where circulating activated CX3CR1+ CD8 T cell numbers are often expanded.

Indexed as

AgedAnimalsAtherosclerosisCD8-Positive T-LymphocytesChemokine CX3CL1Endothelial CellsHIV InfectionsHumansInterleukin-15Macaca mulattaReceptors, ChemokineChemokine CX3CL1CX3CL1 protein, humanIL15 protein, humanInterleukin-15Receptors, Chemokine

Identifiers

PMID32976527
PMCPMC7540902
OpenAlexW3088384336

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.