Mechanisms Regulating Telomerase Activity in Murine T Cells

Machiko Ogoshi, Akira Takashima, R. Stan Taylor

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Abstract

Telomeres shorten with successive cell divisions in normal somatic cells, while telomerase plays an important role in maintaining their lengths. Although telomerase activity was originally described as being expressed exclusively by immortal cells and germline cells, a recently developed PCR-based technique (telomeric repeat amplification protocol (TRAP)) has revealed that normal peripheral blood leukocytes also exhibit this activity following mitogenic stimulation. In this study, we examined mechanisms by which mitogenic stimuli up-regulated telomerase activity in T cells. Splenic T cells freshly isolated from BALB/c mice exhibited only negligible telomerase activity. When stimulated with Con A or immobilized anti-CD3 mAb at 10 μg/ml, they acquired an increased telomerase activity and maximal proliferation. By contrast, T cells treated with a much lower concentration (0.03 μg/ml) of anti-CD3 mAb required exogenous IL-2 for telomerase activation and proliferation. Likewise, adult thymocytes treated with anti-CD3 mAb exhibited telomerase activation and proliferation only in the presence of exogenous IL-2, IL-4, IL-7, or IL-15. Furthermore, IL-2 alone was sufficient for telomerase activation in Con A blasts. These results illustrate a pathway through which cytokine receptors transduce telomerase activation signals in T cells. Although telomerase activation was concomitant with cell growth in normal T cells, we have identified T cell lines that showed discrepancies; the CTLL-2 line showed constitutive telomerase activity regardless of cell proliferative state, whereas the 7-17 line proliferated vigorously in response to IL-2, IL-7, or IL-15, without detectable telomerase activity. Thus, telomerase activity, which is ordinarily associated with proliferation in normal T cells, is not necessarily required or sufficient for cell growth.

Original languageEnglish (US)
Pages (from-to)622-628
Number of pages7
JournalJournal of Immunology
Volume158
Issue number2
StatePublished - Jan 15 1997

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Telomerase
T-Lymphocytes
Interleukin-2
Interleukin-15
Interleukin-7
Telomere Shortening
Cytokine Receptors
Thymocytes
Growth
Interleukin-4
Cell Division
Leukocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Mechanisms Regulating Telomerase Activity in Murine T Cells. / Ogoshi, Machiko; Takashima, Akira; Taylor, R. Stan.

In: Journal of Immunology, Vol. 158, No. 2, 15.01.1997, p. 622-628.

Research output: Contribution to journalArticle

Ogoshi, M, Takashima, A & Taylor, RS 1997, 'Mechanisms Regulating Telomerase Activity in Murine T Cells', Journal of Immunology, vol. 158, no. 2, pp. 622-628.
Ogoshi, Machiko ; Takashima, Akira ; Taylor, R. Stan. / Mechanisms Regulating Telomerase Activity in Murine T Cells. In: Journal of Immunology. 1997 ; Vol. 158, No. 2. pp. 622-628.
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