Clonal expansion of HTLV-1 positive CD8+ cells relies on cIAP-2 but not on c-FLIP expression.
2010
Abstract Here we investigate the mechanisms by which HTLV-1 infection prevents the cell death of CD8 + T cells in vivo . We show that upon natural infection, cloned CD8 + but not CD4 + cells from patients without malignancy become resistant to Fas-mediated cell death and acquire an antiapoptotic transcriptome that includes the overexpression of cIAP-2 and c-FLIP(L) . CD8 + lymphocyte-restricted cIAP-2 overexpression correlates with resistance to Fas-mediated apoptosis and depends on tax expression via NF-KappaB. In contrast, in the same CD8 + cells, the HTLV-1-dependent overexpression of c-FLIP(L) does not correlate with resistance to Fas-mediated cell death nor with tax expression. In the present model, infected CD8 + clones are the only cell subtype in which cIAP-2 expression correlates with resistance to cell death. These results support a role for Tax-dependent cIAP-2 expression in preventing the death of naturally infected CD8 + cells and thereby in their clonal expansion in vivo .
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