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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zidar, DA; Mudd, JC; Juchnowski, S; Lopes, JP; Sparks, S; Park, SS; Ishikawa, M; Osborne, R; Washam, JB; Chan, C; Funderburg, NT; Owoyele, A; Alaiti, MA; Mayuga, M; Orringer, C; Costa, MA; Simon, DI; Tatsuoka, C; Califf, RM; Newby, LK; Lederman, MM; Weinhold, KJ

Published Date

  • February 2016

Published In

Volume / Issue

  • 36 / 2

Start / End Page

  • 389 - 397

PubMed ID

  • 26663396

Pubmed Central ID

  • 26663396

Electronic International Standard Serial Number (EISSN)

  • 1524-4636

Digital Object Identifier (DOI)

  • 10.1161/ATVBAHA.115.306112

Language

  • eng

Conference Location

  • United States