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The effects of T cell activation on hematopoiesis and myeloid cells in atherosclerosis

Sturgess, Wesley (2019) MOBY01 20182
Degree Projects in Molecular Biology
Popular Abstract
Another link in the immune cell chain

Cardiovascular disease (CVD) is the number one cause of death in the western world. The main cause of CVD is atherosclerosis, a chronic inflammatory disease of the major arteries. Atherosclerosis can be described as by a build up of plaque in medium to large arteries. Clinical complications, such as heart attack and stroke, occur when plaques rupture and form clots that block blood flow. Plaques are mainly composed of connective tissues, lipids and dead cells. Plaque progression is due to cholesterol particles passing into plaques and its subsequent recognition by cells of the immune system, causing inflammation. It is understood that the immune system plays a major role in the development of... (More)
Another link in the immune cell chain

Cardiovascular disease (CVD) is the number one cause of death in the western world. The main cause of CVD is atherosclerosis, a chronic inflammatory disease of the major arteries. Atherosclerosis can be described as by a build up of plaque in medium to large arteries. Clinical complications, such as heart attack and stroke, occur when plaques rupture and form clots that block blood flow. Plaques are mainly composed of connective tissues, lipids and dead cells. Plaque progression is due to cholesterol particles passing into plaques and its subsequent recognition by cells of the immune system, causing inflammation. It is understood that the immune system plays a major role in the development of atherosclerosis. Some aspects of this are relatively well understood, whereas others, such as the interplay between T cells and myeloid cells needs to be examined further. T cells recognise foreign particles (antigens) and boost immune responses by recruiting and activating other immune cells. During atherosclerosis T cells are thought to recruit other inflammatory immune cells such as monocytes. Monocytes migrate into plaque and then develop into macrophages that "eat" cholesterol. The purpose of this study was to investigate this interplay between myeloid cells and T cells.

Method
We conducted two experiments in this study. For both experiments we used mice that have high circulating levels of cholesterol and thus develop atherosclerosis. For the first experiment we injected mice with T cells that cause local skin inflammation. The second experiment involved injecting T cell activating protein complexes (IL-2/anti-IL-2) that results in activation of T cells.

Results
Transfer of skin-specific T cells did not impact monocyte numbers. However, there was a significant decrease in monocytes in mice that received T cell activating protein complexes.

Discussion
Our data suggests that the magnitude of T cell activation is important for an affect to be seen in circulating monocytes. However, it is also possible that the timing of the experiments played a key factor in the results. Further investigation closer to the time of treatment may well yield different set of results. We expected an increase in circulating monocytes as a result of increased T cell activation, but this was not the case. It is possible that monocytes left circulation and migrated into the plaques. It will therefore be of great interest to examine cell composition in the plaques. Another step to better understand this phenomenon would be to look at monocyte precursor cells in the bone marrow. In conclusion, our data supports the hypothesis of interplay between T cells and monocytes in mice with atherosclerosis during certain types of T cell activation. This study is a good starting point for investigation into the role of T cells and the influence they have on other immune cells in atherosclerosis and whether they can be manipulated to help treat the disease.

Supervisor: Dr. Daniel Engelbertsen, Experimental Cardiovascular Research, Department of Clinical Sciences, Malmö, Lund University (Less)
Please use this url to cite or link to this publication:
author
Sturgess, Wesley
supervisor
organization
course
MOBY01 20182
year
type
M2 - Bachelor Degree
subject
language
English
id
8973442
date added to LUP
2019-03-25 11:41:08
date last changed
2019-03-25 11:41:08
@misc{8973442,
  author       = {{Sturgess, Wesley}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{The effects of T cell activation on hematopoiesis and myeloid cells in atherosclerosis}},
  year         = {{2019}},
}