Altered Maturation Status and Possible Immune Exhaustion of CD8 T Lymphocytes in the Peripheral Blood of Patients Presenting With Acute Coronary Syndromes
| Autor: | Robyn Osborne, Samantha R. Stubblefield Park, Robert M. Califf, Jeffrey B. Washam, Michael M. Lederman, Cliburn Chan, Nicholas T. Funderburg, Masakazu Ishikawa, Adeyinka Owoyele, Carl E. Orringer, Mohamad Amer Alaiti, Steven M Juchnowski, Daniel I. Simon, David A. Zidar, Myttle Mayuga, Curtis Tatsuoka, Kent J. Weinhold, Marco A. Costa, Joseph C. Mudd, Joao Pedro Lopes, Sara D. Sparks, L. Kristin Newby |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Interleukin 2 Male medicine.medical_treatment Programmed Cell Death 1 Receptor Inflammation 030204 cardiovascular system & hematology Biology CD8-Positive T-Lymphocytes Lymphocyte Activation Article Immunophenotyping 03 medical and health sciences 0302 clinical medicine Immune system medicine Cytotoxic T cell Humans Acute Coronary Syndrome Cells Cultured Aged Interleukin Middle Aged Flow Cytometry Lipoproteins LDL 030104 developmental biology Cytokine Phenotype Case-Control Studies Immunology Interleukin-2 Female medicine.symptom Cardiology and Cardiovascular Medicine Immunologic Memory CD8 Biomarkers medicine.drug |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 36(2) |
| ISSN: | 1524-4636 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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