Prevention of autoimmune diabetes by immune tolerance to proinsulin
- Research Opportunity
- PhD, Masters by Research, Honours, Master of Biomedical Science
- Project Status
- Medicine and Radiology
- St Vincent's Hospital
|Prof Tom Kay||Personal web page|
|Dr Bala Krishnamurthy||Personal web page|
Insulin is the primary target of autoimmunity in the non-obese diabetic (NOD) mice and perhaps in humans. Diabetes in NOD mice is preventable by induction of tolerance to proinsulin from birth, but it remains to be investigated if such an approach will be effective in the clinical setting of established insulitis. After antigen specific tolerance induction, it is necessary to assess if the strategy of tolerance induction actually worked. In human clinical trials using insulin for tolerance induction, it is not clear if tolerance was actually achieved. Even the studies establishing insulin as the primary antigen in NOD mice, T-cell tolerance to insulin was not demonstrated in a direct manner due to lack of a reliable T-cell assay to detect rare autoantigen specific T cells.
Therefore, clinically important questions are whether induction of tolerance to the primary antigen will be effective when introduced late in the disease process and can the tolerance be demonstrated directly by analyzing the number or /and function of antigen specific T cells.
We have generated transgenic NOD mouse model to conditionally express proinsulin in antigen presenting cells at different stages of disease progression. Using this model we will study at what stage in disease process tolerance strategy directed towards insulin is effective. A sensitive tetramer and magnetic bead enrichment protocol has been developed within the Immunology and Diabetes Unit. We will use this assay to enumerate the low frequency of insulin specific T cells before and after the introduction of insulin specific tolerance.
This project is conducted in St Vincent’s Institute of Medical Research, Immunology Unit.
Faculty Research Themes
School Research Themes
PhD, Masters by Research, Honours, Master of Biomedical Science Graduate Research Students who are interested in joining this project will need to consider their elegibility as well as other Graduate Research requirements before contacting the supervisor of this research
For further information about this research, please contact a supervisor.