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

老年人很容易受到感染。这表明免疫缺陷在衰老过程中发生。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，这是我们年轻时健康的一个非常有效的保障。然而，随着年龄的增长，这些细胞失去活力，这可能解释了感染发生率的增加。为了启动免疫反应，需要进行大规模的招募活动，以动员免疫大军。招募增加了清除感染所必需的细胞毒性战斗人员的数量。这种增加发生在细胞毒性细胞被诱导分裂和增殖时。我们以前的数据表明，老年人的细胞毒性细胞不像年轻人的细胞那样分裂，因为这些细胞中一种重要的酶端粒酶失去了活性。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调查旧的细胞毒性T细胞中端粒酶缺陷的性质，以确定这些变化是否可逆。这对于改善老年人的健康状况具有明显的意义。我们提出的研究是基于我们以前的数据，这些数据是通过BBSRC基金产生的，是这项工作的逻辑后续。

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.