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

270 Citations (Scopus)

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+CD28null 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+CD28null 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+CD28null 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

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Acute Coronary Syndrome
Endothelial Cells
T-Lymphocytes
Unstable Angina
Human Umbilical Vein Endothelial Cells
Perforin
KIR Receptors
C-Reactive Protein
Strontium
Acute-Phase Proteins
Exocytosis
Wounds and Injuries
T-Lymphocyte Subsets
T-Cell Antigen Receptor
Major Histocompatibility Complex
Clone Cells

Keywords

  • Apoptosis
  • Coronary disease
  • Endothelium
  • Lymphocytes
  • Plaque

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

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

T-cell-mediated lysis of endothelial cells in acute coronary syndromes. / Nakajima, Takako; Schulte;, Stephanie; Warrington, Kenneth J; Kopecky, Stephen L.; Frye, Robert L.; Goronzy, Jörg J.; Weyand, Cornelia M.

In: Circulation, Vol. 105, No. 5, 05.02.2002, p. 570-575.

Research output: Contribution to journalArticle

Nakajima, T, Schulte;, S, Warrington, KJ, Kopecky, SL, Frye, RL, Goronzy, JJ & Weyand, CM 2002, 'T-cell-mediated lysis of endothelial cells in acute coronary syndromes', Circulation, vol. 105, no. 5, pp. 570-575. https://doi.org/10.1161/hc0502.103348
Nakajima T, Schulte; S, Warrington KJ, Kopecky SL, Frye RL, Goronzy JJ et al. T-cell-mediated lysis of endothelial cells in acute coronary syndromes. Circulation. 2002 Feb 5;105(5):570-575. https://doi.org/10.1161/hc0502.103348
Nakajima, Takako ; Schulte;, Stephanie ; Warrington, Kenneth J ; Kopecky, Stephen L. ; Frye, Robert L. ; Goronzy, Jörg J. ; Weyand, Cornelia M. / T-cell-mediated lysis of endothelial cells in acute coronary syndromes. In: Circulation. 2002 ; Vol. 105, No. 5. pp. 570-575.
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AU - Goronzy, Jörg J.

AU - Weyand, Cornelia M.

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N2 - 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+CD28null 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+CD28null 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+CD28null 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.

AB - 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+CD28null 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+CD28null 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+CD28null 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.

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KW - Endothelium

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