{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:50:37Z","timestamp":1789509037148,"version":"build-2803163510"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Inflammation 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              We used polychromatic flow cytometry to analyze the cytokine production profiles of na\u00efve, 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\n              <jats:sup>+<\/jats:sup>\n              T-cell maturation subsets with reduced proportions of na\u00efve cells and expansion of effector memory cells. ACS was also accompanied by impaired interleukin-2 production by phenotypically na\u00efve CD8 T cells. These results were validated in a second replication cohort. Na\u00efve 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 na\u00efve CD8 T cells.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              In this exploratory analysis, na\u00efve CD8\n              <jats:sup>+<\/jats:sup>\n              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.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.115.306112","type":"journal-article","created":{"date-parts":[[2015,12,11]],"date-time":"2015-12-11T04:18:22Z","timestamp":1449807502000},"page":"389-397","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Altered Maturation Status and Possible Immune Exhaustion of CD8 T Lymphocytes in the Peripheral Blood of Patients Presenting With Acute Coronary Syndromes"],"prefix":"10.1161","volume":"36","author":[{"given":"David A.","family":"Zidar","sequence":"first","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C.","family":"Mudd","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Juchnowski","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao P.","family":"Lopes","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Sparks","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha S.","family":"Park","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Osborne","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B.","family":"Washam","sequence":"additional","affiliation":[{"name":"From 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.); 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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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeyinka","family":"Owoyele","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad A.","family":"Alaiti","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myttle","family":"Mayuga","sequence":"additional","affiliation":[{"name":"From 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..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Orringer","sequence":"additional","affiliation":[{"name":"From 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.); 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