Fujii H, Shao L, Colmegna I et al. Proc Natl Acad Sci USA 2009;106:4360–5.
Age is an important risk factor in the development of rheumatoid arthritis (RA). With increasing age, naïve T cells are increasingly replenished by autoproliferation and less by thymic production owing to the involution of the thymus with older age. The length of the telomeres regulates cellular lifespan. Telomere length is regulated by an enzyme called telomerase. In T cells from RA patients, which were activated via the T cell receptor in this study, telomerase insufficiency was observed. This undermines the homeostatic control of the T cell compartment and could thereby lead to autoimmunity owing to a lack of regulatory capacity of the T cell compartment towards autoreactive T cell clones. This is relevant because it provides an explanation as to why older people more frequently develop RA than younger people, and allows for the possibility of developing drugs that restore the telomerase insufficiency in RA.
Chronically stimulated T lymphocytes sustain the tissue-destructive joint inflammation that occurs in rheumatoid arthritis (RA). In RA, both naïve and memory T cells are prematurely aged, with a reduction in T cell receptor diversity and impaired clonal expansion; however, the mechanisms underlying this finding are unclear.