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You are here: Home / Teams / Alternative splicing and tumoral progression - D. Auboeuf / Publications / Clonal expansion of HTLV-1 positive CD8+ cells relies on cIAP-2 but not on c-FLIP expression.

Clonal expansion of HTLV-1 positive CD8+ cells relies on cIAP-2 but not on c-FLIP expression.

Linda Zane, David Sibon, Catherine Legras, Joel Lachuer, Anne Wierinckx, Patrick Mehlen, Marie-Helene Delfau-Larue, Antoine Gessain, Olivier Gout, Christiane Pinatel, Agnes Lancon, Franck Mortreux, and Eric Wattel (2010)

Virology, 407(2):341-51.

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 toFas-mediated cell death and acquire an antiapoptotic transcriptome that includesthe 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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