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(Circulation Research. 2003;93:106.)
© 2003 American Heart Association, Inc.

Clinical Research

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

From the Departments of Medicine (T.N., O.G., X.Z., S.L.K., R.L.F., J.J.G., C.M.W.) and Immunology (J.J.G., C.M.W.), Mayo Clinic, Rochester, Minn.

Correspondence to Cornelia M. Weyand, MD, Guggenheim 401, 200 First St SW, Mayo Clinic, Rochester, MN 55905. E-mail weyand.cornelia{at}mayo.edu

The inflammatory infiltrate in atherosclerotic plaque is composed of T cells and macrophages. CD4⁺ T cells with a unique phenotype, CD4⁺CD28^null, 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⁺CD28^null T-cell cytolytic function. In patients with acute coronary syndromes (ACS), CD4⁺CD28^null 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⁺CD28^null 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⁺CD28^null T cells, allowing them to kill in the absence of T-cell receptor triggering. Our data demonstrate that CD4⁺CD28^null 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.

Key Words: killer immunoglobulin-like receptors • plaque instability • inflammation • unstable angina • myocardial infarction

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