Human T cell leukemia virus-I (HTLV-I) tax-mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state

Marek Los, Khashayarsha Khazaie, Klaus Schulze-Osthoff, Patrick A. Baeuerle, Volker Schirrmacher, Katerina Chlichlia

Research output: Contribution to journalArticle

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Abstract

We have shown that an estradiol-dependent activation of human T cell leukemia virus-I Tax leads to the inhibition of cell proliferation and to the induction of apoptosis. The present study demonstrates that a hormone- dependent activation of Tax promotes an enhanced prooxidant state in stably transfected Jurkat cells as measured by changes in the intracellular levels of glutathione and H2O2; these changes are followed by apoptotic cell death. Additional stimulation of the CD3/TCR pathway enhances the oxidative and apoptotic effects. Both Tax-mediated apoptosis and oxidative stress can be potently suppressed by antioxidants, as is seen with the administration of recombinant thioredoxin (adult T cell leukemia-derived factor) or pyrrolidine dithiocarbamate. Hormone-induced Tax activation induces a long-lasting activation of NF-κB, which is a major target of reactive oxygen intermediates. The long-term exposure of Jurkat cells to hormone eventually results in a selection of cell clones that have lost Tax activity. A subsequent transfection of these apparently 'nonresponsive' clones allows the recovery of Tax responses in these cells. Our observations indicate that changes in the intracellular redox status may be a determining factor in Tax- mediated DNA damage, apoptosis, and selection against the long-term expression of Tax function.

Original languageEnglish (US)
Pages (from-to)3050-3055
Number of pages6
JournalJournal of Immunology
Volume161
Issue number6
StatePublished - Sep 15 1998
Externally publishedYes

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Human T-lymphotropic virus 1
Jurkat Cells
Hormones
Apoptosis
T-Lymphocytes
Clone Cells
Thioredoxins
DNA Damage
Oxidation-Reduction
Transfection
Glutathione
Estradiol
Oxidative Stress
Cell Death
Antioxidants
Cell Proliferation
Oxygen

ASJC Scopus subject areas

  • Immunology

Cite this

Los, M., Khazaie, K., Schulze-Osthoff, K., Baeuerle, P. A., Schirrmacher, V., & Chlichlia, K. (1998). Human T cell leukemia virus-I (HTLV-I) tax-mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state. Journal of Immunology, 161(6), 3050-3055.

Human T cell leukemia virus-I (HTLV-I) tax-mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state. / Los, Marek; Khazaie, Khashayarsha; Schulze-Osthoff, Klaus; Baeuerle, Patrick A.; Schirrmacher, Volker; Chlichlia, Katerina.

In: Journal of Immunology, Vol. 161, No. 6, 15.09.1998, p. 3050-3055.

Research output: Contribution to journalArticle

Los, M, Khazaie, K, Schulze-Osthoff, K, Baeuerle, PA, Schirrmacher, V & Chlichlia, K 1998, 'Human T cell leukemia virus-I (HTLV-I) tax-mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state', Journal of Immunology, vol. 161, no. 6, pp. 3050-3055.
Los, Marek ; Khazaie, Khashayarsha ; Schulze-Osthoff, Klaus ; Baeuerle, Patrick A. ; Schirrmacher, Volker ; Chlichlia, Katerina. / Human T cell leukemia virus-I (HTLV-I) tax-mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state. In: Journal of Immunology. 1998 ; Vol. 161, No. 6. pp. 3050-3055.
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