Programmed cell death (PCD) encompasses a broad range of molecular signalling pathways that regulate the controlled destruction of our cells, in a contextually appropriate way. Apoptosis is the most well studied pathway, by which damaged, infected or superfluous cells are eliminated from our bodies via an ‘immunologically silent’ mechanism. By contrast, necroptosis and pyroptosis are inflammatory cell death programs that promote immune inflammation via the release of damage associated molecular patterns, and/or inflammatory cytokines.
Little is known regarding the usage of necroptotic and pyroptotic pathways by T cells, although emerging evidence demonstrates that T cells can utilise these pathways in several contexts of disease and inflammation. Using mucosal associated invariant T (MAIT) cells as a reference, this project will interrogate the molecular regulation of inflammatory cell death pathways using a variety of methods, including: flow cytometry, western blotting, ELISA, tissue culture, mouse models, plate-based viability assays and enzyme activity assays. Using these methods, this project seeks to identify the situations in which T cell subsets utilise inflammatory cell death signalling, and how this contributes to immunity more broadly.