Evidence map›Paper›PMID 26663396›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Altered Maturation Status and Possible Immune Exhaustion of CD8 T Lymphocytes in the Peripheral Blood of Patients Presenting With Acute Coronary Syndromes.

David A Zidar, Joseph C Mudd, Steven Juchnowski, Joao P Lopes, Sara Sparks, Samantha S Park, Masakazu Ishikawa, Robyn Osborne, Jeffrey B Washam, Cliburn Chan and 12 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

17 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. CD8Nature reviews. Cardiology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Epigenetics · 2022
    Article
  8. Article
  9. Review
  10. Article
  11. Adaptive Immune Responses in Human Atherosclerosis.International journal of molecular sciences · 2020
    Review
  12. Article
  13. Article
  14. Genome-wide DNA methylome alterations in acute coronary syndrome.International journal of molecular medicine · 2018
    Article
  15. [Oxidized low-density lipoprotein modulates differentiation of murine memory CD8Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017
    Article
  16. Article
  17. 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

22 authors at 6 institutions in 1 country.

David A ZidarFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.). David.Zidar@UHhospitals.org.
Joseph C MuddFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Steven JuchnowskiFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Joao P LopesFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Sara SparksFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Samantha S ParkFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Masakazu IshikawaFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Robyn OsborneFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Jeffrey B WashamFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Cliburn ChanFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Nicholas T FunderburgFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Adeyinka OwoyeleFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Mohamad A AlaitiFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Myttle MayugaFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Carl OrringerFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Marco A CostaFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Daniel I SimonFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Curtis TatsuokaFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Robert M CaliffFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
L Kristin NewbyFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Michael M LedermanFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Kent J WeinholdFrom the Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve, University School of Medicine, Cleveland, OH (D.A.Z., S.J., J.P.L., M.I., M.A.A., M.M., M.A.C., D.I.S.); Division of Infectious Diseases, Department of Medicine (J.C.M., M.M.L.) and Department of Neurology (C.T.), Case Western Reserve University/University Hospitals of Cleveland, OH; Athersys, Inc., Cleveland, OH (S.S.P.); Department of Surgery (S.S., R.O., K.J.W.), Duke Heart Center (J.B.W.), and Department of Biostatistics and Bioinformatics (C.C.), and Duke Clinical Research Institute (R.M.C., L.K.N.), Duke University Medical Center, Durham, NC; Division of Medical Laboratory Science, School of Health and Rehabilitation Sciences, The Ohio State University, Columbus (N.T.F.); Case Western Reserve University School of Medicine, Cleveland, OH (A.O.); and Department of Medicine, University of Miami Health System, FL (C.O.).
Clinical Research Institute · USUniversity Hospitals of Cleveland · USDuke Medical Center · USAthersys (United States) · USCase Western Reserve University · USThe Ohio State University · US

Funding

Case Clinical Trials Unit: Administrative Supplement NOSI AI-20-031.UM1AI069501 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI George Yendewa · 2012 to 2026
$40.4M
Clinical and Translational Science Collaborative of ClevelandKL2TR000440 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$11.1M
Inflammation in Vascular Injury and RepairR37HL057506 · NHLBI · CASE WESTERN RESERVE UNIVERSITY · PI SIMON, DANIEL I · 2007 to 2016
$4.1M
Immunology Training Program-PredoctoralT32AI089474 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI COBB, BRIAN A · 2010 to 2025
$3.4M
NCATS NIH HHS KL2 TR000440NCATS NIH HHS KL2TR000440NHLBI NIH HHS R37 HL057506NIAID NIH HHS T32 AI089474NIAID NIH HHS UM1 AI069501
6 · The paper itself

Abstract

objectiveInflammation in response to oxidized lipoproteins is thought to play a key role in acute coronary syndromes (ACS), but the pattern of immune activation has not been fully characterized. We sought to perform detailed phenotypic and functional analysis of CD8 T lymphocytes from patients presenting with ACS to determine activation patterns and potential immunologic correlates of ACS. APPROACH AND

resultsWe used polychromatic flow cytometry to analyze the cytokine production profiles of naïve, effector, and memory CD8 T cells in patients with ACS compared with control subjects with stable coronary artery disease. ACS was associated with an altered distribution of circulating CD8(+) T-cell maturation subsets with reduced proportions of naïve cells and expansion of effector memory cells. ACS was also accompanied by impaired interleukin-2 production by phenotypically naïve CD8 T cells. These results were validated in a second replication cohort. Naïve CD8 cells from patients with ACS also had increased expression of programmed cell death-1, which correlated with interleukin-2 hypoproduction. In vitro, stimulation of CD8 T cells with oxidized low-density lipoprotein was sufficient to cause programmed cell death-1 upregulation and diminished interleukin-2 production by naïve CD8 T cells.

conclusionsIn this exploratory analysis, naïve CD8(+) T cells from patients with ACS show phenotypic and functional characteristics of immune exhaustion: impaired interleukin-2 production and programmed cell death-1 upregulation. Exposure to oxidized low-density lipoprotein recapitulates these features in vitro. These data provide evidence that oxidized low-density lipoprotein could play a role in immune exhaustion, and this immunophenotype may be a biomarker for ACS.

Indexed as

Lymphocyte ActivationAcute Coronary SyndromeAgedBiomarkersCase-Control StudiesCD8-Positive T-LymphocytesCells, CulturedFemaleFlow CytometryHumansImmunologic MemoryImmunophenotypingInterleukin-2Lipoproteins, LDLMaleMiddle AgedBiomarkersIL2 protein, humanInterleukin-2Lipoproteins, LDLoxidized low density lipoproteinPDCD1 protein, humanProgrammed Cell Death 1 Receptoracute coronary syndromeinflammationinterleukinsoxidized low density lipoproteinprogrammed cell death, type 1

Identifiers

PMID26663396
PMCPMC5079704
OpenAlexW2265874663

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