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Telomerase in T Lymphocytes: Use It and Lose It?¹

Department of Immunology and Molecular Pathology, University College London, London, United Kingdom

The enzyme telomerase counteracts telomere loss in proliferating cells and extends their capacity for replication. The importance of telomerase is highlighted by the award of the 2006 Albert Lasker Prize for Basic Medical Research for its discovery. Malignant cells subvert telomerase induction to their advantage, and up-regulation of this enzyme confers these populations with unlimited proliferative potential with obvious detrimental consequences. However this enzyme is also essential for the lifelong maintenance of normal cell populations that have a high rate of turnover. Thymic involution in early adulthood dictates that memory T cell populations have to be maintained by continuous proliferation. This highlights the inherent paradox that telomerase down-regulation in T cells may protect against malignancy yet also lead to replicative exhaustion of repeatedly activated memory T cells. In this article, we review the data on telomerase regulation in T lymphocytes and the implications this has for the maintenance of T cell memory.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work is supported by Research into Ageing and the Biotechnology and Biological Sciences Research Council.

² Address correspondence and reprint requests to Prof. Arne N. Akbar, Division of Infection and Immunity, University College London, Windeyer Building, 46 Cleveland Street, London W1T 4JF, U.K. E-mail address: a.akbar{at}ucl.ac.uk

³ Abbreviations used in this paper: TERT, telomerase reverse transcriptase; hTERT, human TERT; XLP, X-linked lymphoproliferative syndrome.

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