11Dendritic cells affect plaque stability by the regulation of immunosuppressive processes in atherosclerosis

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Abstract

Purpose

Atherosclerosis is associated with extensive inflammatory processes in the vessel wall, which can result in plaque instability. Dendritic cells (DC), which are characterized by their ability to induce a T-cell specific immune response, play a crucial role in the regulation of inflammatory processes within the atherosclerotic lesions. Apart from that, DCs also have been shown to be involved in immunosuppressive processes, by the interaction with regulatory T-cells, which in turn inhibit DC maturation as well as the proliferation of T-lymphocytes. The aim of our study was to investigate the existence of a possible correlation between the emergence of DCs and regulatory T-cells in atherosclerotic plaques.

Methods

Cross-sections of 30 human carotid endarterectomy specimens were immunohistochemically analysed for the presence of myeloid DC (CD209n + ), regulatory T cells (FOXP3n + ), and COX-2 expressing cells, which are generally increased in the course of inflammation. Classification of atherosclerotic specimens into stable and vulnerable plaques was performed using Trichrome staining.

Results

Plaques were grouped into stable or vulnerable based on their morphological characteristics (content of lipids, thickness of the fibrous cap). As compared with stable plaques, vulnerable lesions were characterized by increased levels of COX-2-positive cells, especially in the plaque shoulders and the fibrous cap, indicating an increased inflammatory process in those regions. In stable plaques, the numbers of CD209 expressing DC were significantly decreased in the plaque shoulder regions, which indicate a reduced immune response, as CD209 mediates DC's rolling interactions with endothelium and activation of CD4n + T cells. On the contrary, the numbers of regulatory T cells were increased in stable as compared to vulnerable plaques. In all investigated plaques (stable and vulnerable plaques) a negative correlation between myeloid DC and regulatory T cells was detected.

Conclusions

Raised numbers of COX-2 positive cells indicate an increased inflammatory state in vulnerable as compared to stable plaques. The negative correlation between myeloid DC and regulatory T-cells suggests an increased differentiation of naïve T lymphocytes into regulatory T-cells in the absence of myeloid DC, which contributes to an enhanced plaque stability.

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