Emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques

Abstract

Dendritic cells (DC), which are critically involved in various immunological disorders, were detected in atherosclerotic plaques in 1995. Since DC might be related to the immunological processes in atherosclerosis (AS), we analyzed the emergence of DC and other inflammatory cells in different stages of AS. Serial cross-sections of 44 carotid specimens were immunohistochemically analyzed for the presence of DC, T cells, macrophages, and HLA-DR. Atherosclerotic specimens were histologically defined as initial lesions, advanced stable, or vulnerable plaques. In initial lesions significantly lower DC numbers were detected than in advanced plaques (P < 0.001). For advanced plaques, DC numbers were significantly higher in vulnerable than in stable plaques (P = 0.005). In contrast to initial lesions, approximately 70% of DC in advanced plaques exhibited a mature phenotype (CD83+, DC-LAMP+), indicating a functional activity of DC. In plaques of patients with acute ischemic symptoms DC numbers were markedly elevated (P = 0.03), whereas significantly lower DC numbers and more often a stable plaque morphology were detected in statin-treated patients (P = 0.02). DC clusters with a strong HLA-DR expression and frequent DC-T cell contacts were located particularly in the rupture-prone plaque regions and at complications. The results of the present study indicate that DC might contribute to plaque destabilization through an activation of T cells.