International Immunology Advance Access originally published online on January 3, 2005
International Immunology 2005 17(2):207-215; doi:10.1093/intimm/dxh201
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© 2005 The Japanese Society for Immunology
Identification of two distinct elements mediating activation of telomerase (hTERT) gene expression in association with cell growth in human T cells
Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Correspondence to: M. Nakamura; E-mail: naka.gene{at}cmn.tmd.ac.jp
Lymphocytes are exceptional among normal somatic cells in that they express high telomerase activity like germline and malignant cells. We investigated the induction of telomerase in human T cells in association with cell growth. IL-2 significantly augmented the expression of mRNA for human telomerase reverse transcriptase (hTERT), a rate-limiting component of telomerase, in PHA-activated human peripheral blood leukocytes. An isolated 5'-flanking sequence (3927+51) of the hTERT gene was examined for its promoter activity in an IL-2-dependent human T cell line Kit 225. Addition of IL-2 into quiescent Kit 225 cells induced activation of the hTERT promoter. Reporter assays with mutant fragments of the hTERT promoter further revealed that IL-2-dependent activation was independently mediated by two elements within the +9+51 regions. The two elements showed similar kinetics of activation in response to IL-2, which coincided with the G1 to S phase transition of the cell cycle. Interestingly, introduction of mutation in the elements increased background promoter activities in resting T cells in the absence of IL-2. Our results demonstrate that the hTERT promoter may be suppressed by the elements and IL-2 may signal for de-suppression in association with promotion of cell growth. IL-2-dependent activation of the hTERT promoter may be necessary for prevention from senescence induced by extraordinary cell division during immune reactions.
Keywords: gene regulation, hTERT, IL-2, T lymphocytes