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, oxi dative DNA damage has been shown to accumulate in human T cell clones in vi tro grown under standard culture conditions. Work on fibroblasts has demons trated that telomeres are particularly susceptible to oxidative damage, whi ch they are unable to repair. The importance of oxidative stress in the ind uction of human cell DNA damage and alteration of proliferative potential i s supported by the findings that fibroblast strains with a very good antiox idant capacity have a reduced rate of telomere shortening and extended life span in vitro, when compared to fibroblast strains with lower antioxidant c apacity. 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 outco me of which may be the generation of fewer T cells following an antigenic s timulus, so resulting in a less effective immune response. Interventions ai med at slowing down the accumulation of such DNA damage and/or telomere sho rtening may have a major impact on the maintenance of an efficient immune r esponse with increasing age.