Date of Award


Degree Type


Degree Name

Master of Science


Microbiology and Immunology


Dr. Terry Delovitch

Second Advisor

Dr. Joaquin Madrenas

Third Advisor

Dr. Bhagirath Singh


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.



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