Expression and regulation of telomerase in human T cell differentiation, activation, aging and diseases

Telomeres are essential for chromosomal integrity. Telomere shortening during cell division restricts cellular proliferative capacity and leads to cellular senescence when critically shortened telomere lengths are reached. Similar to hematopoietic stem cells, T cells can upregulate telomerase activity to compensate for telomere loss incurred during proliferation in response to engagement of the T cell antigen receptor (TCR) or exposure to homeostatic cytokines. However, this compensation for telomere loss by telomerase in T cells is imperfect or limited, as shortening of T cell telomeres is observed in human aging and during in vitro longterm culture. In this review, we summarize the current state of knowledge regarding the expression and regulation of telomerase in human T cells and changes of telomerase expression during development, activation, differentiation, aging and disease conditions. In conclusion, we discuss how controlled enhancement of telomerase activity could be a potential strategy to improve T cell function in the elderly and in immunotherapy.