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- Title
HTLV-1 propels untransformed CD4<sup>+</sup> lymphocytes into the cell cycle while protecting CD8<sup>+</sup> cells from death.
- Authors
Sibon, David; Gabet, Anne-Sophie; Zandecki, Marc; Pinatel, Christiane; Thête, Julien; Delfau-Larue, Marie-Hélène; Rabaaoui, Samira; Gessain, Antoine; Gout, Olivier; Jacobson, Steven; Mortreux, Franck; Wattel, Eric
- Abstract
Human T cell leukemia virus type 1 (HTLV-1) infects both CD4+ and CD8+ lymphocytes, yet it induces adult T cell leukemia/lymphoma (ATLL) that is regularly of the CD4+ phenotype. Here we show that in vivo infected CD4+ and CD8+ T cells displayed similar patterns of clonal expansion in carriers without malignancy. Cloned infected cells from individuals without malignancy had a dramatic increase in spontaneous proliferation, which predominated in CD8+ lymphocytes and depended on the amount of tax mRNA. In fact, the clonal expansion of HTLV-1-positive CD8+ and CD4+ lymphocytes relied on 2 distinct mechanisms - infection prevented cell death in the former while recruiting the latter into the cell cycle. Cell cycling, but not apoptosis, depended on the level of viral-encoded tax expression. Infected tax-expressing CD4+ lymphocytes accumulated cellular defects characteristic of genetic instability. Therefore, HTLV-1 infection establishes a preleukemic phenotype that is restricted to CD4+ infected clones.
- Subjects
ADULT T-cell leukemia; HTLV-I; LYMPHOCYTES; MESSENGER RNA; CELL cycle; CELL death
- Publication
Journal of Clinical Investigation, 2006, Vol 116, Issue 4, p974
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI27198