Regulation and function of telomerase in T cells

National Institute On Aging

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Abstract

Telomerase activity is tightly regulated during T cell development, differentiation, and activation. In human peripheral blood resting T cells, telomerase activity is low to undetectable despite telomerase reverse transcriptase (TERT) is detected. Alternate splicing of TERT is found in activated T cells, but it is unclear whether the full-length and alternative splicing of TERT exist in every individual T cell or different T cell contains different forms of TERT. It is also unclear whether lack of telomerase activity in resting T cells is a result of non-functional splicing products (ASP) of TERT mRNA and/or missing proper post-translational modifications of TERT protein. To address these questions, we applied single cell RT-PCR method for analyzing TERT full-length and ASP in resting and activated T cells. We found that 1) 39% of the resting T cells expressed only full-length TERT, 34% expressed both full-length and ASP, and 27% expressed only TERT ASP;and 2) activation led to the loss of expressing only full-length TERT cells and an increase of only TERT ASP cells. Intriguingly, the level of telomerase activity increased significantly from resting to activated T cells despite of higher percentage of activated T cells containing TERT ASP. Current study will address this seemingly paradoxical finding.