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

Linda Zane; David Sibon; Catherine Legras; Joël Lachuer; Anne Wierinckx; Patrick Mehlen; Marie-Hélène Delfau-Larue; Antoine Gessain; Olivier Gout; Christiane Pinatel; Agnès Lançon; Franck Mortreux; Eric Wattel

doi:10.1016/j.virol.2010.07.023

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

Virology. 2010 Nov 25;407(2):341-51. doi: 10.1016/j.virol.2010.07.023. Epub 2010 Sep 22.

Authors

Linda Zane¹, David Sibon, Catherine Legras, Joël Lachuer, Anne Wierinckx, Patrick Mehlen, Marie-Hélène Delfau-Larue, Antoine Gessain, Olivier Gout, Christiane Pinatel, Agnès Lançon, Franck Mortreux, Eric Wattel

Affiliation

¹ CNRS UMR5239, Université de Lyon, Oncovirologie et Biothérapies, Centre Léon Bérard, 69008 Lyon, France.

PMID: 20863547
DOI: 10.1016/j.virol.2010.07.023

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis*
Baculoviral IAP Repeat-Containing 3 Protein
CASP8 and FADD-Like Apoptosis Regulating Protein / genetics
CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism*
CD4-Positive T-Lymphocytes / cytology
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / virology
CD8-Positive T-Lymphocytes / cytology
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / virology*
Cell Proliferation*
Cell Survival
Clone Cells / cytology
Clone Cells / immunology
Clone Cells / virology
Gene Products, tax / genetics
Gene Products, tax / metabolism
HTLV-I Infections / immunology
HTLV-I Infections / virology
Human T-lymphotropic virus 1 / immunology
Human T-lymphotropic virus 1 / pathogenicity*
Humans
Inhibitor of Apoptosis Proteins / genetics
Inhibitor of Apoptosis Proteins / metabolism*
Ubiquitin-Protein Ligases
fas Receptor / metabolism

Substances

CASP8 and FADD-Like Apoptosis Regulating Protein
Gene Products, tax
Inhibitor of Apoptosis Proteins
fas Receptor
BIRC3 protein, human
Baculoviral IAP Repeat-Containing 3 Protein
Ubiquitin-Protein Ligases