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Altered Maturation Status and Possible Immune Exhaustion of CD8 T Lymphocytes in the Peripheral Blood of Patients Presenting With Acute Coronary Syndromes.
Zidar, David A; Mudd, Joseph C; Juchnowski, Steven; Lopes, Joao P; Sparks, Sara; Park, Samantha S; Ishikawa, Masakazu; Osborne, Robyn; Washam, Jeffrey B; Chan, Cliburn; Funderburg, Nicholas T; Owoyele, Adeyinka; Alaiti, Mohamad A; Mayuga, Myttle; Orringer, Carl; Costa, Marco A; Simon, Daniel I; Tatsuoka, Curtis; Califf, Robert M; Newby, L Kristin; Lederman, Michael M; Weinhold, Kent J.
Afiliação
  • Zidar DA; 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 Depa
  • Mudd JC; 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 Depa
  • Juchnowski S; 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 Depa
  • Lopes JP; 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 Depa
  • Sparks S; 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 Depa
  • Park SS; 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 Depa
  • Ishikawa M; 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 Depa
  • Osborne R; 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 Depa
  • Washam JB; 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 Depa
  • Chan C; 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 Depa
  • Funderburg NT; 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 Depa
  • Owoyele A; 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 Depa
  • Alaiti MA; 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 Depa
  • Mayuga M; 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 Depa
  • Orringer C; 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 Depa
  • Costa MA; 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 Depa
  • Simon DI; 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 Depa
  • Tatsuoka C; 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 Depa
  • Califf RM; 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 Depa
  • Newby LK; 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 Depa
  • Lederman MM; 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 Depa
  • Weinhold KJ; 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 Depa
Arterioscler Thromb Vasc Biol ; 36(2): 389-97, 2016 Feb.
Article em En | MEDLINE | ID: mdl-26663396
ABSTRACT

OBJECTIVE:

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. APPROACH AND

RESULTS:

We 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.

CONCLUSIONS:

In 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ativação Linfocitária / Linfócitos T CD8-Positivos / Síndrome Coronariana Aguda Tipo de estudo: Diagnostic_studies / Observational_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Arterioscler Thromb Vasc Biol Assunto da revista: ANGIOLOGIA Ano de publicação: 2016 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ativação Linfocitária / Linfócitos T CD8-Positivos / Síndrome Coronariana Aguda Tipo de estudo: Diagnostic_studies / Observational_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Arterioscler Thromb Vasc Biol Assunto da revista: ANGIOLOGIA Ano de publicação: 2016 Tipo de documento: Article