A number of research studies have demonstrated inflammation's role in fuelling plaque buildup, also known as atherosclerosis, which is the underlying cause of most heart attacks and strokes, but knowledge of which immune cells are key to this process has been limited – until now.
Researchers at the La Jolla Institute for Allergy & Immunology have
identified the specific type of immune cells (CD4 T cells) that
orchestrate the inflammatory attack on the artery wall. Further, the
researchers discovered that these immune cells behave as if they have
previously seen the antigen that causes them to launch the attack.
"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," said Klaus Ley, M.D., a renowned expert in
vascular immunology, who led the study in mouse models. "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."
What the researchers found
Dr Ley said he believes the antigen involved is actually a normal
protein that the body mistakes as being foreign and therefore launches
an immune attack resulting in inflammation in the arteries.
"Essentially, we're saying that there appears to be a strong autoimmune
component in heart disease," he said, explaining that autoimmune
diseases result from the body's mistaken attack on normal cells.
"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."
The study was published online in the Journal of Clinical Investigation in a paper entitled "Dynamic T cell–APC interactions sustain chronic inflammation in atherosclerosis."
Vaccine still a few years off
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."
Dr Ley said antigen-presenting cells take up infectious organisms,
foreign materials and self-proteins (in the case of autoimmune diseases)
and "chop them into little pieces called epitopes" and then display the
pieces on the surface of the cell. "The T cell comes along, and if it
has the correct receptors, it will recognise the epitope pieces and make
cytokines (a type of immune system soldier molecule) that attack the
material and cause inflammation." Autoimmune diseases include such
illnesses as type 1 diabetes, rheumatoid arthritis and multiple
sclerosis.
In the study, Dr Ley and his team used live cell imaging techniques to
track immune cells in normal and artherosclerotic mouse aortas. He said
in mice with atherosclerosis, there are a large number of
antigen-experienced T cells that have already seen certain epitope
pieces (from self proteins) that they perceive as foreign.
"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 fat
and cholesterol to form artery-clogging plaque that can eventually
block blood flow, leading to a heart attack.
"It wasn't previously known that antigen-experienced T cells existed in
the vessel wall," said Dr Ley. "This experiment makes me now believe
that it may be possible to build a vaccine for heart disease."
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Health24