Date of Award
2009
Degree Type
Thesis
Degree Name
Master of Science
Program
Microbiology and Immunology
Supervisor
Dr. Terry Delovitch
Second Advisor
Dr. Joaquin Madrenas
Third Advisor
Dr. Bhagirath Singh
Abstract
Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease resulting from the destruction of pancreatic islet |3 cells. The non-obese diabetic (NOD) mouse is a model for T1D. a-GalCer activates iNKT cells and reduces incidence of T1D in the NOD mouse. It is a potent iNKT cell agonist whose effects are not specific for T1D. Structural modifications to a-GalCer were made and tested in the NOD mouse in an attempt to optimize glycolipid-mediated protection from T1D. We found that PBS-25 exacerbated T1D whereas PBS-24 protected against T1D. PBS-25 failed to elicit a TH2-bias shift in cytokine secretion, decreased iNKT cell frequency in the pancreatic lymph nodes (PLN), and did not induce tolerogenic DCs. Conversely, PBS-24 caused a Tn2-bias shift in cytokine secretion, reduced islet inflammation while maintaining iNKT cell frequency in the PLN. This structure/function correlation provides insight into the optimization of glycolipids specific for the treatment of T1D.
Recommended Citation
Blumenfeld, Hartley J., "OPTIMIZING GLYCOLIPIDS FOR THE TREATMENT OF TYPE 1 DIABETES" (2009). Digitized Theses. 3884.
https://ir.lib.uwo.ca/digitizedtheses/3884