T-cell-mediated lysis of endothelial cells in acute coronary syndromes

Takako Nakajima, Stephanie Schulte, Kenneth J. Warrington, Stephen L. Kopecky, Robert L. Frye, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticle

274 Scopus citations

Abstract

Background - CD4 T lymphocytes accumulate in unstable plaque. The direct and indirect involvement of these T cells in tissue injury and plaque instability is not understood. Methods and Results - Gene profiling identified perforin, CD161, and members of the killer-cell immunoglobulin-like receptors as being differentially expressed in CD4 + CD28 null T cells, a T-cell subset that preferentially infiltrates unstable plaque. Frequencies of CD161 + and perforin-expressing CD4 T cells in peripheral blood were significantly increased in patients with unstable angina (UA). CD161 appeared on CD4 + CD28 null T cells after stimulation, suggesting spontaneous activation of circulating CD4 T cells in UA. Perforin-expressing CD4 + T-cell clones from patients with UA exhibited cytotoxic activity against human umbilical vein endothelial cells (HUVECs) in redirected cytotoxicity assays after T-cell receptor triggering and also after stimulation of major histocompatibility complex class I-recognizing killer-cell immunoglobulin-like receptors. HUVEC cytolysis was dependent on granule exocytosis, as demonstrated by the paralyzing effect of pretreating CD4 + CD28 null T cells with strontium. Incubation of HUVECs with C-reactive protein (CRP) increased HUVEC lysis in a dose-dependent fashion. Conclusions - In patients with UA, CD4 T cells undergo a change in functional profile and acquire cytotoxic capability. Cytotoxic CD4 T cells effectively kill endothelial cells; CRP sensitizes endothelial cells to the cytotoxic process. We propose that T-cell-mediated endothelial cell injury is a novel pathway of tissue damage that contributes to plaque destabilization. The sensitizing effect of CRP suggests synergy between dysregulated T-cell function and acute phase proteins in acute coronary syndromes.

Original languageEnglish (US)
Pages (from-to)570-575
Number of pages6
JournalCirculation
Volume105
Issue number5
DOIs
StatePublished - Feb 5 2002

Keywords

  • Apoptosis
  • Coronary disease
  • Endothelium
  • Lymphocytes
  • Plaque

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Nakajima, T., Schulte, S., Warrington, K. J., Kopecky, S. L., Frye, R. L., Goronzy, J. J., & Weyand, C. M. (2002). T-cell-mediated lysis of endothelial cells in acute coronary syndromes. Circulation, 105(5), 570-575. https://doi.org/10.1161/hc0502.103348