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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1208.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Interleukin-15 Expression in Atherosclerotic Plaques

An Alternative Pathway for T-Cell Activation in Atherosclerosis?

Mischa A. Houtkamp; Allard C. van der Wal; Onno J. de Boer; Chris M. van der Loos; Piet A. J. de Boer; Antoon F. M. Moorman; Anton E. Becker

From the Departments of Cardiovascular Pathology (M.A.H., A.C.W., O.J.B., C.M.L., A.E.B.) and Anatomy and Embryology (P.A.J.B., A.F.M.M.), Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.

Correspondence to Anton E. Becker, MD, Department of Cardiovascular Pathology, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, Netherlands. E-mail m.i.schenker{at}amc.uva.nl

Abstract—T-cell activation in atherosclerotic plaques is thought to be initiated by plaque-derived antigens, such as oxidized LDL (oxLDL). An alternative pathway of T-cell activation independent of antigen stimulation, mediated by the cytokine interleukin (IL)-15, was recently described. We investigated IL-15 expression in atherosclerotic plaques in relation to plaque morphology, inflammatory cells, T-cell activation, and oxidation-specific epitopes by use of immunohistochemistry. In situ hybridization was used to evaluate IL-15 mRNA expression. We also studied the proliferative response of plaque-derived T-cell lines to IL-15 in vitro using [³H]thymidine incorporation. Fresh-frozen specimens were classified as fibrous (n=9), fibrolipid (n=8), and lipid-rich (n=14) plaques; normal vessels (n=4) served as reference. Expression of IL-15 mRNA and protein was found almost solely in fibrolipid and lipid-rich plaques, associated with oxLDL-positive macrophages. Sequential immunostains revealed colocalization between IL-15– and CD40L-positive T cells. Moreover, plaque-derived T-cell lines were highly responsive to IL-15. Hence, IL-15 could provide a pathway for antigen-independent T-cell activation.

Key Words: cell-mediated immunity • interleukin-15 • macrophages • T-cell activation

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