De novo expression of killer immunoglobulin-like receptors and signaling proteins regulates the cytotoxic function of CD4 T cells in acute coronary syndromes

Takako Nakajima, Ömer Goek, Xiaoyu Zhang, Stephen L. Kopecky, Robert L. Frye, Jörg J. Goronzy, Cornelia M. Weyand

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

The inflammatory infiltrate in atherosclerotic plaque is composed of T cells and macrophages. CD4+ T cells with a unique phenotype, CD4+CD28null, are preferentially recruited into culprit lesions. These T cells are distinct from classic CD4+CD28+ T cells in gene expression and function, including their ability to mediate cytolysis. In this study, we have investigated the regulation of CD4+CD28null T-cell cytolytic function. In patients with acute coronary syndromes (ACS), CD4+CD28null T cells express killer immunoglobulin-like receptors (KIRs). KIRs encompass a polymorphic family of receptors that recognize HLA class I molecules and have been implicated in self-tolerance. CD4+CD28null T-cell clones from patients with ACS and age-matched controls were compared for their KIR-expression profile. T-cell clones derived from the patients expressed a broader spectrum of KIRs (P<0.001) with preference for the stimulatory variant, CD158j. Additionally, CD4+ T-cell clones from patients but not those from controls acquired de novo expression of the DAP12 molecule, an adapter chain that transmits CD158j-derived signals. Cumulative expression of CD158j and DAP12 endowed cytolytic competence on CD4+CD28null T cells, allowing them to kill in the absence of T-cell receptor triggering. Our data demonstrate that CD4+CD28null T cells in ACS are characterized by a unique gene expression profile. Consequently, these T cells acquire cytolytic capability that can bypass the need for T-cell receptor triggering and, thus, impose a threat to self-tolerance.

Original languageEnglish (US)
Pages (from-to)106-113
Number of pages8
JournalCirculation research
Volume93
Issue number2
DOIs
StatePublished - Jul 25 2003

Keywords

  • Inflammation
  • Killer immunoglobulin-like receptors
  • Myocardial infarction
  • Plaque instability
  • Unstable angina

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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