Date of Award
2009
Degree Type
Thesis
Degree Name
Master of Science
Program
Microbiology and Immunology
Supervisor
Dr. Terry Delovitch
Second Advisor
Dr. Mansour Haeryfar
Third Advisor
Dr. Bhagi Singh
Abstract
Type 1 diabetes (T1D) results from the destruction of pancreatic islet P cells by self-reactive T cells. Treatment of non-obese diabetic (NOD) mice with the potent iNKT cell agonist a-galactosylceramide C26:0 (a-GalCer) or its TH2-biasing derivative a- galactosylceramide C20:2 (C20:2) confers protection against T1D. After an initial response to a-GalCer, iNKT cells become anergic, exhibiting a significantly blunted response upon subsequent restimulation. Although anergic iNKT cells are more susceptible to apoptosis, they are also responsible for inducing tolerogenic dendritic cells (DCs) upon restimulation, which play an important role in the protection against T1D. My results demonstrate that C20:2 activated iNKT cells enter and recover from anergy more rapidly than a-GalCer, leading to reduced iNKT cell death and the induction of more tolerogenic DCs after a multi-low dose treatment protocol. I propose that these characteristics of C20:2 may render it a more promising drug candidate for the treatment of T1D than a-GalCer.
Recommended Citation
Tohn, Robert, "THE ROLE OF INVARIANT NATURAL KILLER T (iNKT) CELL ANERGY IN GLYCOLIPID-MEDIATED PROTECTION AGAINST TYPE 1 DIABETES (T1D)" (2009). Digitized Theses. 4001.
https://ir.lib.uwo.ca/digitizedtheses/4001