Cited by 859Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsNuclear Structure and Function

The DOI matches its Crossref record.

Activation of telomerase in human lymphocytes and hematopoietic progenitor cells

Hiyama, K, Hirai, Y, Kyoizumi, S, Akiyama, M, Hiyama, E, Piatyszek, M A, Shay, J W, Ishioka, S, Yamakido, M·1995·The Journal of Immunology

DOI 10.4049/jimmunol.155.8.3711

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Abstract

This is the first report describing up-regulation of telomerase activity in human normal cells. Telomerase, a ribonucleoprotein enzyme, has been thought to be involved in maintaining telomere length stability in germline and most cancer cells, but not in normal cells. However, in the present study, we demonstrate that telomerase activity is detectable at low levels in normal human T and B cells, increases by in vitro mitogenic stimulation, increases in hematopoietic progenitor cells upon their proliferation and differentiation, and decreases with aging. Understanding the regulation of telomerase activity in normal cells may provide important insights not only into the mechanisms of normal cellular senescence but also into the mechanisms of telomerase activity deregulation as part of cancer development.

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“This may explain the need for relatively high telomerase activity to maintain telomere length homeostasis in this cell compartment during an immune response.(39,41) Thus, age-related declines in telomerase activity may compromise stem cell-mediated tissue repair, germ cell viability, and immune cell function in humans.”
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“Telomerase activity has been reported to be elevated in some highly proliferative somatic cells.(13,14) We previously demonstrated that mitogenic stimuli like cotinine could activate telomerase in human VSMCs.”
Background
Granulomatous Disease Associated with Bartonella Infection in 2 Dogs
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“In this framework, the mitogen stimulation applied in this work was intended to switch on TA in circulating lymphocytes as expressed prior their differentiation [Hiyama et al., 1995b; Yamada et al., 1996].”
BackgroundMethod
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Background
Interleukin 6 receptor expression by human cord blood‐ or peripheral blood‐derived primitive haematopoietic progenitors implies acquisition of different functional properties
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“E-mail: sonoda@basic.kpu-m.ac.jp It was recently reported that primitive human haematopoietic stem/progenitor cells exhibit a low level of telomerase activity (Hiyama et al, 1995; Chiu et al, 1996; Morrison et al, 1996).”
Background
Telomerase is not activated in human hyperplastic and adenomatous parathyroid tissue
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Background
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Background
Activation of Telomerase Is Induced by a Natural Antigen in Allergen-Specific Memory T Lymphocytes in Bronchial Asthma
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Self-citation
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“Hiyama et al and Igarashi et al have demonstrated induction of telomerase activity in B lymphocytes after a subset of stimuli such as mitogens, anti-IgM antibodies, and anti-CD40 monoclonal antibody (11, 12).”
Background
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“Also telomerase expression has been described in tissues with high proliferation levels, such as haematopoietic cells [ 12 ], basal cells of the epidermis [13] and cells from the intestinal crypt [14].”
Background
Possible molecular mechanisms underlying the development of atherosclerosis in cancer survivors
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“As a result, telomerase activity is considered to be a biological index of cell proliferation rather than malignancy [3,4].”
Background
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Telomerase activity might persist in the human thymus throughout life
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“A cell extract of 1 µL (1000 cells) was used for TRAP assay to avoid the false-positive result by contaminating lymphocytes, which have weak telomerase activity ( 15 ).”
BackgroundMethodInfluentialSelf-citation
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“…in vitro and in primary tumour tissues, most fetal tissues, and normal adult male reproductive cells and represents an important difference between normal somatic cells and cancer cells (Kim et al, 1994; Hiyama et al, 1995; Rhyu, 1995; Wright et al, 1996; Shay and Bacchetti, 1997; Sedivy, 1998).”
Background
The significance of telomerase activity in cancer lesions and the noncancerous epithelium of the esophagus
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Background
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BackgroundInfluential
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“demonstrated that leukocytes constitutively express low levels of TA [31].”
Background
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Self-citation
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Background
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“Human tissue stem cells, such as haematopoietic stem cells, have some telomerase activity (Broccoli et al., 1995; Hiyama et al., 1995) and have been used for transplantation to patients (Cutler and Antin, 2001; Nivison-Smith et al.”
BackgroundMethod
Telomeres and Estrogens: The Unholy Nexus in Pathogenesis of Atherosclerosis
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“activated lymphocytes and certain types of stem cells [18-20].”
Background
Contributions of Telomere Biology to Human Age-Related Disease
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Tight co-twin similarity of monozygotic twins for hTERT protein level of T cell subsets, for telomere length and mitochondrial DNA copy number, but not for telomerase activity
Melicher, D., Illés, A., Pállinger, É., Kovács, Á. F., Littvay, L., Tárnoki, Á. D., Tárnoki, D. L., Bikov, A., Molnár, M. J., Buzás, E. I., et al. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2738-z · Cited by 8
Decreased numbers of signal-joint T cell receptor excision circle-containing CD4+ and CD8+ cells in systemic lupus erythematosus patients
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“Telomerase activity is known as an indicator of increased lymphocyte division.(4) We reported that peripheral lymphocytes from SLE patients had a high telomerase activity, suggesting the active division of peripheral blood lymphocytes from SLE patients.”
Background
A high-throughput assay for a human telomerase protein–human telomerase RNA interaction
Keppler, B. R., & Jarstfer, M. B. (2006) · Analytical Biochemistry · doi:10.1016/j.ab.2006.03.027 · Cited by 7
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Telomerase activity detected in eyed embryos of rainbow trout Oncorhynchus mykiss
YODA, M., Takahashi, K., & Mori, K. (2002) · Fisheries Science · doi:10.1046/j.1444-2906.2002.00398.x · Cited by 7
Telomerase activity of Merkel cell carcinomas and Merkel cell carcinoma-derived cell cultures
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Increased telomerase activity and absence of p53 mutation in oligo-astrocytomas induced by N-ethyl-N-nitrosourea in rats
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Background
Telomeres and Cell Division Potential
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Comparison of telomerase activity between malignant and tuberculous pleural effusions.
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Tuberculin purified protein derivative up-regulates the telomerase activity of peripheral blood mononuclear cells from patients with pulmonary tuberculosis
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Regulation of Telomerase Activity
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“Our results concerning telomerase activity in peripheral lymphocytes and inducibility of the enzyme are well in line with the recent publications on this issue [4, 6, 7, 11, 17, 33].”
BackgroundResult
Inhibition of telomerase in canine cancer cells following telomestatin treatment
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Self-citation
Immortalization of Human and Rhesus Macaque Primary Antigen‐Specific T Cells by Retrovirally Transduced Telomerase Reverse Transcriptase
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“Circulating quiescent T cells do not express TERT; however, TERT activity is sharply elevated in activated human T cells (Hiyama et al., 1995; Weng et al., 1996, 1997a,b, 1998; Haruta et al., 1999) and may play a role in supporting the survival, proliferation, and expansion of antigen-responding T…”
Background
Targeting Telomerase in Hematologic Malignancy
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Background
Telomerase activity and apoptosis genes as parameters of lymphocyte aging in Down syndrome patients
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“This mechanism is crucial for the suicide of activated T cells and macrophages [29].”
Background
Promoter CpG methylation inhibits Krüppel-like factor 2 (KLF2)-Mediated repression of hTERT gene expression in human T-cells
Mizuguchi, M., Hara, T., Yoshita‐Takahashi, M., Kohda, T., Tanaka, Y., & Nakamura, M. (2021) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2021.100984 · Cited by 5
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“In general, telomerase is inhibited in inflammatory cells (21,22).”
Background
Telomerase and non-Telomerase Mechanisms of Telomere Maintenance
Morrish, T. A. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.73734 · Cited by 6
Role of RIN1 on telomerase activity driven by EGF-Ras mediated signaling in breast cancer
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Immunohistochemical expression of telomerase in patients with non-small cell lung cancer: prediction of metastasis and prognostic significance.
Aras, G., Kanmaz, D., Urer, N., Purısa, S., Kadakal, F., Yentürk, E., & Tuncay, E. (2013) · PubMed · Cited by 5

Authors: Hiyama, K., Hirai, Y., Kyoizumi, S., Akiyama, M., Hiyama, E., Piatyszek, M. A., Shay, J. W., Ishioka, S., & Yamakido, M.
Affiliations: Hiroshima University (JP)
ORCID: Akiyama, M
Hiyama, E
Piatyszek, M A
Shay, J W
Ishioka, S
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 1995-10
Volume: 155
Issue: 8
Pages: 3711-3715
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.155.8.3711
OpenAlex: W1516272650
Cited by: 853
References: 0
Citations by year: 2026: 1 · 2025: 4 · 2024: 2 · 2023: 10 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 13 · 2018: 11 · 2017: 8 · 2016: 13 · 2015: 15 · 2014: 17 · 2013: 20 · 2012: 17
FWCI: 38.21
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG07992, R01AG007992)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords: telomerase, telomerase activity, lymphocytes, T cells, B cells, hematopoietic progenitor cells, mitogen stimulation, aging, cellular senescence, telomere length, carcinogenesis, normal cells
MeSH terms: Adolescent, Adult, Aged, Aged, 80 and over, Aging, Base Sequence, Bone Marrow Cells, Cell Separation, Child, Child, Preschool, Enzyme Activation, Hematopoietic Stem Cells, Humans, Infant, Infant, Newborn, Leukocytes, Mononuclear, Lymphocyte Activation, Lymphocytes, Male, Middle Aged, Molecular Sequence Data, Telomerase

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Activation of telomerase in human lymphocytes and hematopoietic progenitor cells

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