The impact of TCR-activation and IL-2Rβ signaling in atherosclerosis
(2019) MOBN02 20182Degree Projects in Molecular Biology
- Abstract
- Atherosclerosis, a chronic inflammatory condition, is the main attributor to cardiovascular disease. As such, elucidating the underlying immunological events that occur during atherogenesis has become an area of interest to better understand atherosclerotic pathology. T cells are an integral component of the adaptive immune response and have been shown to be present in atherosclerotic plaques. However, their exact atherosclerotic role is still to be discerned. In this study, we aimed to clarify the role of T cell activation in atherosclerosis. Our approach was two-fold. First, we utilized the Nur77GFP atherosclerotic reporter mouse to determine if T cell receptor (TCR)-activated T cells are present in atherosclerotic plaques, as the... (More)
- Atherosclerosis, a chronic inflammatory condition, is the main attributor to cardiovascular disease. As such, elucidating the underlying immunological events that occur during atherogenesis has become an area of interest to better understand atherosclerotic pathology. T cells are an integral component of the adaptive immune response and have been shown to be present in atherosclerotic plaques. However, their exact atherosclerotic role is still to be discerned. In this study, we aimed to clarify the role of T cell activation in atherosclerosis. Our approach was two-fold. First, we utilized the Nur77GFP atherosclerotic reporter mouse to determine if T cell receptor (TCR)-activated T cells are present in atherosclerotic plaques, as the current paradigm suggests. Secondly, we treated atherosclerotic mice with interleukin (IL)-2 complexed to an anti-IL-2 antibody, S4B6, to determine if cytokine activated T cells can have atherogenic effects. Our results suggest that contrary to current belief, TCR-activated T cells are not present in atherosclerotic plaques. Furthermore, treatment with IL-2/S4B6 had contradictory atherosclerotic effects, decreasing total plasma cholesterol while increasing levels of plaque-resident macrophages. (Less)
- Popular Abstract
- How does your immune system effect your heart health?
Cardiovascular disease is the leading cause of death worldwide. The major cause of heart attacks and strokes is atherosclerosis, the build-up of fatty deposits, or plaques, within the walls of large and medium-sized blood vessels. These plaques begin when “bad cholesterol” passes out of the blood and into the walls of the blood vessel. When this occurs, it causes an inflammation within the vessel wall, which recruits immune cells to the blood vessel. If the inflammation persists, the plaque may become large enough to block the blood flow in that vessel.
T cells are a part of the immune system that can elicit very specific protection against foreign materials, such as viruses and... (More) - How does your immune system effect your heart health?
Cardiovascular disease is the leading cause of death worldwide. The major cause of heart attacks and strokes is atherosclerosis, the build-up of fatty deposits, or plaques, within the walls of large and medium-sized blood vessels. These plaques begin when “bad cholesterol” passes out of the blood and into the walls of the blood vessel. When this occurs, it causes an inflammation within the vessel wall, which recruits immune cells to the blood vessel. If the inflammation persists, the plaque may become large enough to block the blood flow in that vessel.
T cells are a part of the immune system that can elicit very specific protection against foreign materials, such as viruses and bacteria. However, T cells may also react towards self-tissue and molecules, such as cholesterol and blood vessels. Since being found in atherosclerotic plaques, T cells have become a cell of interest in understanding the disease progression of atherosclerosis. It has been speculated that the T cells contributing to the disease are present in the plaque and use very specific receptors on its cell surface to become activated and react towards the plaque itself. Therefore, the first aim of our study was to determine if these specifically activated T cells are truly located within the atherosclerotic plaques. Furthermore, T cells are also capable of becoming activated in a non-specific manner, via detection of chemicals that are secreted by other immune cells from anywhere in the body. Thus, our second aim in this study was to determine if T cells activated in a non-specific manner can also affect atherosclerosis.
In order to determine if specific T cells are located within the plaque, we used a mouse model that can easily detect specifically activated T cells, as these T cells will glow green following activation via their cell surface receptors. We took cell samples from multiple organs and tissues including the aorta, where plaques are located. We detected no green T cells in the aorta sample, suggesting that T cells activated specifically are not present in the plaque. To determine if T cells activated in a non-specific manner influence atherosclerosis, we injected mice with a complex capable of activating all types of T cells and studied the effect on the plaques. Our results showed an increase in immune cells present in the plaque, which has been shown to worsen atherosclerosis. Interestingly, we also saw a decrease in total cholesterol levels, which may be an effect that could help slow the progression of atherosclerosis.
Collectively, our studies indicate that specifically activated T cells are not present in the aorta, or at least not substantially. Furthermore, T cells that are activated non-specifically are also capable of causing atherogenic effects. Together, our results oppose the current view of the role of T cells in atherosclerosis. There have been multiple studies trying to design vaccines to prevent the progression of atherosclerosis by targeting at attenuating plaque-specific T cells. However, our results indicate this type of treatment may not be useful in atherosclerosis. In order to generate new therapies targeting the immune system in atherosclerosis, further studies clarifying the role of T cells may be necessary.
Master’s Degree Project in Molecular Biology, 45 credits 2019
Department of Biology, Lund University
Advisor: Daniel Engelbertsen
Experimental Cardiovascular Research Unit, Department of Clinical Sciences in Malmö, Lund University, Clinical Research Center, Skåne University Hospital, SE-20502 Malmö, Sweden (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/8990078
- author
- Mulholland, Megan
- supervisor
- organization
- course
- MOBN02 20182
- year
- 2019
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 8990078
- date added to LUP
- 2019-07-04 16:19:20
- date last changed
- 2019-07-04 16:19:20
@misc{8990078,
abstract = {{Atherosclerosis, a chronic inflammatory condition, is the main attributor to cardiovascular disease. As such, elucidating the underlying immunological events that occur during atherogenesis has become an area of interest to better understand atherosclerotic pathology. T cells are an integral component of the adaptive immune response and have been shown to be present in atherosclerotic plaques. However, their exact atherosclerotic role is still to be discerned. In this study, we aimed to clarify the role of T cell activation in atherosclerosis. Our approach was two-fold. First, we utilized the Nur77GFP atherosclerotic reporter mouse to determine if T cell receptor (TCR)-activated T cells are present in atherosclerotic plaques, as the current paradigm suggests. Secondly, we treated atherosclerotic mice with interleukin (IL)-2 complexed to an anti-IL-2 antibody, S4B6, to determine if cytokine activated T cells can have atherogenic effects. Our results suggest that contrary to current belief, TCR-activated T cells are not present in atherosclerotic plaques. Furthermore, treatment with IL-2/S4B6 had contradictory atherosclerotic effects, decreasing total plasma cholesterol while increasing levels of plaque-resident macrophages.}},
author = {{Mulholland, Megan}},
language = {{eng}},
note = {{Student Paper}},
title = {{The impact of TCR-activation and IL-2Rβ signaling in atherosclerosis}},
year = {{2019}},
}