Human T Cell Differentiation Negatively Regulates Telomerase Expression Resulting in Reduced Activation-Induced Proliferation and Survival

• Published in: Frontiers in immunology Vol. 10; p. 1993
• Main Authors: Patrick, Michael S., Cheng, Nai-Lin, Kim, Jaekwan, An, Jie, Dong, Fangyuan, Yang, Qian, Zou, Iris, Weng, Nan-ping
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 21.08.2019
• Subjects: alternative splicing; differentiation; hTERT; Immunology; T cell subsets; T lymphocytes; telomerase; T lymphocytes; differentiation; telomerase; alternative splicing; proliferation; aging; hTERT; T cell subsets
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.01993

Maintenance of telomeres is essential for preserving T cell proliferative responses yet the precise role of telomerase in human T cell differentiation, function, and aging is not fully understood. Here we analyzed human telomerase reverse transcriptase (hTERT) expression and telomerase activity in six T cell subsets from 111 human adults and found that levels of hTERT mRNA and telomerase activity had an ordered decrease from naïve (T ) to central memory (T ) to effector memory (T ) cells and were higher in CD4 than their corresponding CD8 subsets. This differentiation-related reduction of hTERT mRNA and telomerase activity was preserved after activation. Furthermore, the levels of hTERT mRNA and telomerase activity were positively correlated with the degree of activation-induced proliferation and survival of T cells . Partial knockdown of hTERT by an anti-sense oligo in naïve CD4 cells led to a modest but significant reduction of cell proliferation. Finally, we found that activation-induced levels of telomerase activity in CD4 T and T cells were significantly lower in old than in young subjects. These findings reveal that hTERT/telomerase expression progressively declines during T cell differentiation and age-associated reduction of activation-induced expression of hTERT/telomerase mainly affects naïve CD4 T cells and suggest that enhancing telomerase activity could be a strategy to improve T cell function in the elderly.