The Role of V{gamma}4+ V{gamma}3+ T Cells in the Autoimmune Destruction of Pancreatic {beta} Cells in Nonobese Diabetic Mice
Open Access
- Author:
- Huber, Christopher Ryan
- Area of Honors:
- Immunology and Infectious Disease
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Na Xiong, Thesis Supervisor
Na Xiong, Thesis Supervisor
James Endres Howell, Thesis Honors Advisor
Anthony Paul Schmitt, Faculty Reader - Keywords:
- V{gamma}4+ V{gamma}3+ T cells
Autoimmune Destruction
Pancreatic {beta} cells
Nonobese Diabetic Mice - Abstract:
- Type 1 diabetes is an autoimmune disease that attacks the β cells forming in the pancreatic islets. The result is a cease in insulin production which may cause problems in the utilization of glucose. Without insulin, plasma glucose concentration increases while the body begins to degrade its own protein and fat sources, leading to problems such as ketoacidosis, hyperglycemic coma, atherosclerosis, blindness, and even death. A tentative solution to this problem is to administer insulin injections for the remainder of the individual’s life. Insulin injections provide the body with a means of absorbing plasma glucose into the body’s cells for energy production and essential homeostatic functions. Insulin injections can be complicated and come with inherit risk, making them a non-ideal fix to the problem, yet the only way in which individuals suffering from this disease can relieve the issue of destroyed β cells and decreased insulin production. Delving further into the molecular level of this disease, the role of T cells becomes evident in the progression of type 1 diabetes. Scientists are not sure as to the exact cause, but it has been observed that T cells attack pancreatic β cells and cause their destruction. This suggests that type 1 diabetes might result from a dys-regulated immune T cell activation that destroys the body’s β cells. Experiments that have examined the mechanism behind T cell autoimmune destruction of the β cells range from T cell recognition, antigen presentation, thymic selection, memory characteristics, and regulatory functions. My thesis deals with the γδ T cell, a specific sub type of T cell. Specifically, I observed whether knocking out the Vγ4+ Vγ3+ T cells would increase the prevalence of diabetes and quicken diabetes onset in Nonobese Diabetic (NOD) mice, a type 1 diabetes model. Results were measured by obtaining blood glucose samples from two sets of mice, knockout and wild-type mice. The wild-type mice contained functional Vγ4+ Vγ3+ T cells, providing a source of comparison for the knockout mice which did not contain these specific T cells. For a period of 27 weeks, blood glucose levels were recorded and it was observed that higher percentages of the knockout NOD mice became diabetic. Also, diabetes onset occurred much earlier in the knockout mice than was observed in the wild-type mice, indicating a possible regulatory role of the Vγ4+ Vγ3+ γδ T cell in diabetes onset and progression. Each mouse that survived to the conclusion of the experiment had their pancreas removed, sectioned, and put through a hematoxylin and eosin (HE) staining. Under microscopic analysis, the health of each islet of Langerhans correlated to the genotype of the mouse and blood glucose level. Those of the knockout genotype had progressively unhealthy, insulitis ridden islets that were severely atrophied while those of the wild-type genotype generally had healthier, larger islets with less insulitis. This suggests that Vγ4+ Vγ3+ γδ T cells may play a regulatory role in the progression of type 1 diabetes mellitus in NOD mice.