Clonal expansion of HTLV-1 positive CD8+ cells relies on cIAP-2 but not on c-FLIP expression.
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.
Zane
Linda
L
CNRS UMR5239, Université de Lyon, Oncovirologie et Biothérapies, Centre Léon Bérard, 69008 Lyon, France.
Sibon
David
D
Legras
Catherine
C
Lachuer
Joël
J
Wierinckx
Anne
A
Mehlen
Patrick
P
Delfau-Larue
Marie-Hélène
MH
Gessain
Antoine
A
Gout
Olivier
O
Pinatel
Christiane
C
Lançon
Agnès
A
Mortreux
Franck
F
Wattel
Eric
E
D017209:Apoptosis; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology*; D049109:Cell Proliferation; D002470:Cell Survival; D002999:Clone Cells / Q000166:cytology / Q000276:immunology / Q000821:virology; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism; D015490:HTLV-I Infections / Q000276:immunology / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D019014:fas Receptor / Q000378:metabolism
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D016356:Gene Products, tax; D051034:Inhibitor of Apoptosis Proteins; D019014:fas Receptor; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases