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

老年人很容易受到感染。这表明在衰老过程中会出现免疫缺陷。然而，这种缺陷在分子水平上的性质尚不清楚。免疫系统的关键保护细胞之一是细胞毒性T淋巴细胞，它是我们年轻时非常有效的健康保障。然而，随着我们年龄的增长，这些细胞失去活力，这可能解释了感染发生率增加的原因。为了发动免疫反应，有一场大规模的招募活动，以动员免疫大军。招募增加了细胞毒性战斗人员的数量，这是清除感染所必需的。当细胞毒细胞被诱导分裂和增殖时，这种增加就会发生。我们之前的数据表明，老年人的细胞毒细胞不会像年轻人的细胞那样分裂，因为这些细胞中的一种关键酶-端粒酶的活性丢失。这种酶赋予细胞无限的增殖能力。我们在这里提出的研究是为了调查旧的细胞毒性T细胞中端粒酶缺陷的性质，以期确定这些变化是否可逆。这对改善老年受试者的健康状况具有明显的意义。我们提出的研究是基于我们之前通过BBSRC资金产生的数据，是这项工作的合乎逻辑的后续。

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.