DNA damage and telomere length in human T cells

Levels of DNA damage have been shown to increase as a function of age in T cells ex vivo and in vitro. With increasing age, shortening of the terminal ends of chromosomes (telomeres) in T cells has been found. Reactive oxygen species, produced during a normal immune response, are likely to be major contributors to the background levels of DNA damage in T cells. Indeed, oxidative DNA damage has been shown to accumulate in human T cell clones in vitro grown under standard culture conditions. Work on fibroblasts has demonstrated that telomeres are particularly susceptible to oxidative damage, which they are unable to repair. The importance of oxidative stress in the induction of human cell DNA damage and alteration of proliferative potential is supported by the findings that fibroblast strains with a very good antioxidant capacity have a reduced rate of telomere shortening and extended lifespan in vitro, when compared to fibroblast strains with lower antioxidant capacity. An age-related accumulation of DNA damage and telomere shortening in T cells may lead to cell death and/or cell cycle arrest/delay, the outcome of which may be the generation of fewer T cells following an antigenic stimulus, so resulting in a less effective immune response. Interventions aimed at slowing down the accumulation of such DNA damage and/or telomere shortening may have a major impact on the maintenance of an efficient immune response with increasing age.