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 language | English (US) |
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Pages (from-to) | 570-575 |
Number of pages | 6 |
Journal | Circulation |
Volume | 105 |
Issue number | 5 |
DOIs | |
State | Published - Feb 5 2002 |
Keywords
- Apoptosis
- Coronary disease
- Endothelium
- Lymphocytes
- Plaque
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)