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Telomerase Mediates Lymphocyte Proliferation but Not the Atherosclerosis-Suppressive Potential of Regulatory T-Cells

Lookup NU author(s): Dr Gavin RichardsonORCiD, Dr Karim Bennaceur, Emily Dookun, Lilia Draganova, Dr Gabriele Saretzki, Professor Ioakim SpyridopoulosORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Objective—Atherosclerosis is an age-related disease characterized by systemic oxidative stress and low-grade inflammation. The role of telomerase and telomere length in atherogenesis remains contentious. Short telomeres of peripheral leukocytes are predictive for coronary artery disease. Conversely, attenuated telomerase has been demonstrated to be protective for atherosclerosis. Hence, a potential causative role of telomerase in atherogenesis is critically debated.Approach and Results—In this study, we used multiple mouse models to investigate the regulation of telomerase under oxidative stress as well as its impact on atherogenesis in vitro and in vivo. Using primary lymphocytes and myeloid cell cultures, we demonstrate that cultivation under hyperoxic conditions induced oxidative stress resulting in chronic activation of CD4+ cells and significantly reduced CD4+ T-cell proliferation. The latter was telomerase dependent because oxidative stress had no effect on the proliferation of primary lymphocytes isolated from telomerase knockout mice. In contrast, myeloid cell proliferation was unaffected by oxidative stress nor reliant on telomerase. Telomerase reverse transcriptase deficiency had no effect on regulatory T-cell (Treg) numbers in vivo or suppressive function ex vivo. Adoptive transfer of telomerase reverse transcriptase/– Tregs into Rag2–/– ApoE–/– double knockout mice demonstrated that telomerase function was not required for the ability of Tregs to protect against atherosclerosis. However, telomere length was critical for Treg function.Conclusions—Telomerase contributes to lymphocyte proliferation but plays no major role in Treg function, provided that telomere length is not critically short. We suggest that oxidative stress may contribute to atherosclerosis via suppression of telomerase and acceleration of telomere attrition in Tregs.

Publication metadata

Author(s): Richardson G, Sage A, Bennaceur K, Al Zhrany N, Coelho-Lima J, Dookun E, Draganova L, Saretzki G, Breault D, Mallat Z, Spyridopoulos I

Publication type: Article

Publication status: Published

Journal: Arteriosclerosis, Thrombosis, and Vascular Biology

Year: 2018

Volume: 38

Issue: 6

Pages: 1283-1296

Print publication date: 01/06/2018

Online publication date: 29/03/2018

Acceptance date: 05/03/2018

Date deposited: 05/04/2018

ISSN (print): 1079-5642

ISSN (electronic): 1524-4636

Publisher: American Heart Association


DOI: 10.1161/ATVBAHA.117.309940

PubMed id: 29599138


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Funder referenceFunder name
PG/15/85/31744British Heart Foundation