It is no secret that heart disease is still the USA’s No. 1 killer, but not many are aware that cholesterol is greatly assisted by the immune system’s inflammatory cells in causing dangerous arterial plaque buildup that can trigger a heart attack. Various studies have provided evidence that inflammation plays a role in promoting the buildup of plaque (atherosclerosis), which is responsible for the majority of heart attacks and strokes. However, until now, researchers only had limited knowledge of which immune cells play a major role in this process.
The online edition of the Journal of Clinical Investigation reports that La Jolla Institute for Allergy & Immunology researchers have now discovered which specific type of immune cells, in this case CD4 T cells, are involved in the inflammatory attack on the artery wall, and that these CD4T cells behave as if they have previously seen the antigen that causes them to launch the attack.
Leading researcher Klaus Ley, M.D., a renowned expert in vascular immunology, remarks:
“The thing that excites me most about this finding is that these immune cells appear to have ‘memory’ of the molecule brought forth by the antigen-presenting cells. Immune memory is the underlying basis of successful vaccines. This means that conceptually it becomes possible to consider the development of a vaccine for heart disease.”
According to Dr. Ley’s belief, the antigen involved is actually a normal protein which is mistakenly recognized by the body as a foreign material; the body’s immune system’s attack results in inflammation in the arteries. He explains: “Essentially, we’re saying that there appears to be a strong autoimmune component in heart disease. Consequently, we could explore creating a “tolerogenic” vaccine, such as those now being explored in diabetes, which could induce tolerance by the body of this self-protein to stop the inflammatory attack.”
Dr. Ley cautions that creating a vaccine is a complex process that could take years to develop. However it offers exciting potential. “If successful, a tolerogenic vaccine could stop the inflammation component of heart disease,” he said. “This could probably be used in conjunction with the statins (cholesterol-lowering drugs) that have already taken a significant chunk out of the numbers of people with heart disease. Together, they could deliver a nice one-two punch that could be important in further reducing heart disease.”
He explains that antigen-presenting cells take up infectious organisms, foreign materials and in the case of autoimmune diseases self-proteins, which are then “chopped into little pieces called epitopes” before displaying the pieces on the surface of the cell. He continues: “The T cell comes along, and if it has the correct receptors, it will recognize the epitope pieces and make cytokines (a type of immune system soldier molecule) that attack the material and cause inflammation.”
Autoimmune diseases include illnesses like multiple sclerosis, type 1 diabetes and rheumatoid arthritis.
For their study, the team used live cell imaging techniques to track immune cells in normal and artherosclerotic mouse aortas. Mice with atherosclerosis display a large number of antigen-experienced T cells that have already seen certain epitope pieces from self-proteins that they see as foreign material. Ley adds: “The T cells talk to the antigen-presenting cells and, in response, make cytokines that launch an attack. This is what makes the inflammation in the vessel wall persistent.” Inflammatory cells join lipids and cholesterol to form artery-clogging plaque, which leads to a blockage in the blood flow that can ultimately lead to a heart attack.
Dr. Ley concludes: “It wasn’t previously known that antigen-experienced T cells existed in the vessel wall. This experiment makes me now believe that it may be possible to build a vaccine for heart disease.”
Written by Petra Rattue