Telomerase downregulation in memory CD8+ T cells by cytokine and surface inhibitory receptor signalling

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Old individuals are very susceptible to infections. This suggests that an immune defect occurs during ageing. However, the nature of this defect at the molecular level is not known. One of the key protective cells of the immune system is the cytotoxic T lymphocyte that is a very effective safeguard of our health in youth. However, these cells lose vigour as we age and this may explain the increased incidence of infection. To mount an immune response, there is a massive recruitment drive in order to mobilize the immune army. Recruitment increases the number of cytotoxic combatants that are essentail to clear the infection. This increase occurs as the cytotoxic cell is induced to divide and proliferate. Our previous data has shown that the cytotoxic cells from old individuals do not divide as well as those from young subjects because the activity of a crucial enzyme within these cells known as telomerase is lost. This enzyme confers unlimited proliferative capacity to cells. The studies that we propose here are to investigate the nature of the telomerase defect in old cytotoxic T cells, with a view to determine if thes changes are reversible. This has obvious implications for the improvement of health in old subjects. The studies that we hae proposed are based on our previous data that has been generated through BBSRC funding and is a logical follow-on of this work.