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CD4+ regulatory T cells (Treg) are a specialised subset of CD4+ T cells that suppress damaging inflammation to maintain homeostasis.

We have previously shown that CD4+ Treg greatly reduces the development and progression of established atherosclerotic plaques (Circulation 2012; 126: 1256–1266). Tregs were expanded by cytokine therapy where interleukin-2 (IL-2) was complexed an anti-IL-2 antibody (JES601) which alternates its conformation so that it only interacts with regulatory T cells, and not other T cells including cytotoxic T cells. Treatment expanded regulatory T cells 2.5-fold in mice and greatly suppressed atherosclerosis. Unfortunately, at that time there were no mouse models of vulnerable atherosclerotic plaques.

Utilising available mouse models of vulnerable plaques, we will determine the impact of expanding regulatory T cells on vulnerable plaque pathology and assess whether regulatory T cells just prevent progression of atherosclerosis or have the capability to alter plaque phenotype from vulnerable to stable. An important and novel feature of these studies will be to define the spatial distribution of the regulatory T cells within plaques and their interaction with other 'target' immune cells, in particular activated cytotoxic cells and macrophages. This will be achieved using immunofluorescence, scRNAseq/scATACseq and spatial genomics technologies.

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