Interleukin-15 expression in atherosclerotic plaques - An alternative pathway for T-cell activation in atherosclerosis?

T-cell activation in atherosclerotic plaques is thought to be initiated by plaque-derived antigens, such as oxidized LDL (oxLDL). An alternative pathw ay of T-cell activation independent of antigen stimulation, mediated by the cytokine interleukin (IL)-15, was recently described. We investigated IL-1 5 expression in atherosclerotic plaques in relation to plaque morphology, i nflammatory cells, T-cell activation, and oxidation-specific epitopes by us e of immunohistochemistry. In situ hybridization was used to evaluate IL-15 mRNA expression. We also studied the proliferative response of plaque-deri ved T-cell lines to IL-15 in vitro using [H-3]thymidine incorporation. Fres h-frozen specimens were classified as fibrous (n=9), fibrolipid (n=8), and lipid-rich (n=14) plaques; normal vessels (n=4) served as reference, Expres sion of IL-15 mRNA and protein was found almost solely in fibrolipid and li pid-rich plaques, associated with oxLDL-positive macrophages. Sequential im munostains revealed colocalization between IL-15- and CD40L-positive T cell s. Moreover, plaque-derived T-cell lines were highly responsive to IL-15. H ence, IL-15 could provide a pathway for antigen-independent T-cell activati on.