CD8+ T-cells in Atherosclerosis: mechanistic studies revealing a protective role in the plaque microenvironment

Duijn, J. van (2020)

Doctoral Thesis

Atherosclerosis is the most important underlying process that drives cardiovascular disease, and is characterized by an accumulation of cholesterol which triggers an inflammatory response in the vessel wall. This results in the recruitment of many types of inflammatory cells towards the plaques that form in the vessel wall, among which are CD8+ T-cells. In this thesis, the role of CD8+ T-cells in the advanced stages of lesion development has been investigated, as this is the most clinically relevant stage of the disease. This thesis demonstrates that CD8+ T-cells exert a protective function. We show that the absence of CD8+ T-cells in a mouse model results in less stable atherosclerotic lesions with increased numbers of inflammatory cells. In a subsequent study, we show that CD8+ T-cells express an enzyme that inhibits the inflammatory process. We also show that injecting a specific subset of CD8+ T-cells is protective against the development of atherosclerotic lesions in mice. Importantly, we show that this data can be translated to atherosclerosis development in humans, as we demonstrate similar results using patient material obtained from endarterectomy surgery. Finally, we show that developing therapies directed towards activating CD8+ T-cells may be of value to inhibit the immune response, and thus reduce the risk of cardiovascular disease.

• Atherosclerosis
• Immunology
• T-cells
• CD8+ T-cells
• Liposomal vaccination

• All authors: Duijn, J. van
• Supervisor: Kuiper, J.; Jiskoot, W.
• Co-supervisor: Slütter, B.
• Committee: Irth, H.; Bouwstra, J.A.; Monaco, C.; Lutgens, E.; Ketelhuth, D.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drug Research (LADCR), Faculty of Science, Leiden University
• Date: 2020-04-28
• ISBN (print): 9789463614108
• Sponsorship: Hartstichting