T cell ageing

Like many developed countries, the population of Australia is ageing; with 13.8% of the population currently over the age of 65 and predictions this will reach 19.9% by 2031, this increase is predicted to have a considerable effect on the cost to public health services. Aged individuals exhibit increased susceptibility to and severity of a variety of infections (including influenza), alongside waning vaccine efficacy rates, reflecting diminished adaptive responses to newly encountered pathogens. While ageing likely compromises a number of arms of the immune system, studies in mice and humans have demonstrated that intrinsic defects in CTL immunity are likely to contribute substantially to overall immune dysfunction in aged individuals. Thus, my laboratory aims to fully elucidate both age related CTL deficiencies and the mechanisms underlying them. My research involves the characterization of influenza-specific CD8+ T cell populations to define age related phenotypic and functional changes in greater detail (Figure 4) (Quinn et al, 2016, Proc Natl Acad Sci USA, 113; 1333; Quinn et al, 2018, Cell Reports, 23(12); 3512) in combination with cutting edge molecular analyses on global CD8+ T cell populations to determine key epigenetic and metabolic signatures of aged CTL function (Figure 5). This work will rigorously define basic immunological, epigenetic, and metabolic mechanisms restricting intrinsic CD8+T cell immunity in aged individuals.