0 item $0.00

We have shown that cytotoxic T cells, especially CD8+ T cells (Circulation 2012; 127(9): 1028–1039) are important contributors to vulnerable plaque progression. However, my more recent (unpublished) studies indicate that these cells may be incapable of inducing plaque rupture. Rather they appear to progress plaque pathology to a stage where intraplaque haemorrhage is observed, but not beyond. CD8 T cell cytotoxicity in a hyperlipidemic environment appears to be limited by the expression of PCSK9 that inhibits LDLR-mediated T cell receptor recycling and signalling. In contrast, high intracellular cholesterol content in gamma-delta T cells enhances T cell receptor signaling to increase activation status and proliferation, making them prime candidates as culprits in plaque rupture.

Our preliminary data indicate that gamma-delta T cells contribute to atherosclerosis via cytotoxic mechanisms and will define their importance for vulnerable plaque development. We also have data indicating that gamma-delta T cells accumulate abundantly in regions prone to rupture despite being a small T cell subset. Current understanding on gamma-delta T cell subsets and their activation is very limited, so I will identify subsets with pro-atherogenic properties. This will include immune profiling from vulnerable plaques using 10x chromium scRNAseq/scATACseq technology. Together with detailed FACS profiling and other methodologies, we will proceed to investigate their activation, their cytotoxic effector functions and how they affect other immune cells in atherosclerotic plaques as well as identify gamma-delta T cell-targeted therapies for vulnerable plaques. A better understanding of gamma-delta T cells should enable the identification of novel therapeutic targets for vulnerable plaque management; gamma-delta T cells are present in human plaques.

Student research opportunities

Beginning your research career with one of Australia's largest medical research institutes provides unique opportunities for Masters, Honours and PhD students.

Find out more