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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01993

Human T cell differentiation negatively regulates telomerase expression resulting in reduced activation-induced proliferation and survival

 Michael S. Patrick1, Nai-Lin Cheng1,  Jaekwan Kim1, Jie An1, Fangyuan Dong1,  Iris Zou1 and  Nan-ping Weng1*
  • 1National Institute on Aging (NIA), United States

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 (TN) to central memory (TCM) to effector memory (TEM) 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 in vitro. Partial knockdown of hTERT by an anti-sense oligo in naïve CD4+ cells led to a modest but significant reduction of cell proliferation and increase of apoptosis. Finally, we found that activation-induced levels of hTERT mRNA and telomerase activity in naïve CD4+ T cells were significantly lower in old than in young subjects. These findings reveal that hTERT/telomerase expression declines during T cell differentiation and age-associated reduction of activation-induced expression of hTERT/telomerase mainly affect naïve CD4+ T cells and suggest that enhancing telomerase activity could be a strategy to improve T cell function in the elderly.

Keywords: T lymphocyte (T-cell), T cell subsets, Telomerase (hTERT), differentiation, proliferation, Aging

Received: 11 Feb 2019; Accepted: 07 Aug 2019.

Edited by:

Wanjun Chen, National Institutes of Health (NIH), United States

Reviewed by:

Christopher E. Rudd, Université de Montréal, Canada
Li Wang, Institute of Immunology, Third Military Medical University, China  

Copyright: © 2019 Patrick, Cheng, Kim, An, Dong, Zou and Weng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Nan-ping Weng, National Institute on Aging (NIA), Bethesda, United States, WengN@grc.nia.nih.gov