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 exists in every 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 freshly isolated resting and in vitro 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) in vitro 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. Currently, we are studying the relationship of TERT mRNA (full-length and ASP) and telomerase activity. Telomere shortens in peripheral lymphocytes with age. But it is unknown whether telomerase activity decreases in lymphocytes with age as well. We have followed 200 BLSA participants over an average 5 year time span. We found that telomerase activity declined with age in resting and in vitro activated T cells. Interestingly, we found that telomerase activity declined also in the resting but not in vitro activated B cells. Currently we are testing different in vitro stimulation conditions to determine if the difference of this age-associated decline of telomerase activity between T and B cells is intrinsic or extrinsic (stimulation conditions).

National Institute of Health (NIH)
National Institute on Aging (NIA)
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Institute on Aging
Zip Code
Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko et al. (2016) Relationship between spontaneous ?H2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors. Mutat Res Genet Toxicol Environ Mutagen 802:59-65
Lin, Yun; Damjanovic, Amanda; Metter, E Jeffrey et al. (2015) Age-associated telomere attrition of lymphocytes in vivo is co-ordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions. Clin Sci (Lond) 128:367-77
Najarro, Kevin; Nguyen, Huy; Chen, Guobing et al. (2015) Telomere Length as an Indicator of the Robustness of B- and T-Cell Response to Influenza in Older Adults. J Infect Dis 212:1261-9
Weng, Nan-ping (2012) Telomeres and immune competency. Curr Opin Immunol 24:470-5