Understanding if islet-infiltrating CTL can be identified in peripheral blood as biomarkers of Type 1 diabetes

Research Opportunity
PhD, Masters by Research, Honours, Master of Biomedical Science
Project Status
Future
Department
Medicine and Radiology
Location
St Vincent's Hospital
Supervisor Email Number Webpage
Prof Tom Kay Personal web page
Dr Bala Krishnamurthy Personal web page

Project Details

Autoreactive CD8+ T cells specific for beta cell antigens are detectable in peripheral blood. Enumeration of these peripheral blood autoreactive CD8+ T cells is predictive of diabetes in the NOD mouse. However, it is not known if these are CD8+ T cells about to proceed to islets or if they are CTLs that have exited from the islets and differentiated into effector memory CTLs. Understanding if autoreactive CD8+ T cells represent islet CTLs is important because they provide an opportunity to directly translate our findings on islet CTL. Peripheral blood is the only sample regularly available for analysis in humans.

Using tetramer and magnetic bead enrichment assay we have enumerated the low frequency beta cell antigen specific CTLs in peripheral blood and lymphoid organs. We have determined the frequency of these cells increase in the periphery as the severity of islet inflammation increases. The number of antigen specific CD8+ T cells in the periphery directly correlates with the numbers of CTLs in islets. This suggests the peripheral pool of autoreactive CD8+ T cells is formed by CTLs migrating from within the islet environment. We now plan to examine the phenotype and function of the autoreactive CD8+ T cells in the periphery and compare this to CTLs from islets.

We plan to translate our tetramer enrichment assay to analyse CD8+ T cells in the periphery of patients with type 1 diabetes. The autoreactive CTL pool will be isolated by sequential enrichment and cells analysed for antigen specificity, phenotype and cytotoxic function. As the autoreactive CTLs represent islet pathology then their measurement may provide a valuable non-invasive biomarker of the degree of beta cell destruction. This will be useful for the prediction of diabetes and for monitoring the success of islet transplants or immunotherapies as well as for studying cytotoxic effect or function.

This project is conducted in St Vincent’s Institute of Medical Research, Immunology Unit.



Faculty Research Themes

Infection and Immunology

School Research Themes

Cardiometabolic



Research Opportunities

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

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Key Contact

For further information about this research, please contact a supervisor.

Department

Medicine and Radiology

Research Group / Unit / Centre

Research Node

St Vincent's Hospital