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

• 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-kappa B, which is a major target of reactive oxygen ntermediates. 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 mag be a determining factor in Tax-mediated DNA damage, apoptosis, and selection against the long-term expression of Tax function.

Subject headings

NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)

Keyword

antioxidants

gene-expression

induction

interleukin-2

lymphocytes

nf-kappa-b

protein

redox regulation

thioredoxin

transcription factor

Publication and Content Type

ref (subject category)

art (subject category)