Interleukin 7 increases human immunodeficiency virus type 1 LAI-mediated Fas-induced T-cell death.
Fas-mediated T-cell death is known to occur during human immunodeficiency virus (HIV) infection. In this study, we found that HIV type 1 LAI (HIV-1(LAI)) primes CD8(+) T cells from healthy donors for apoptosis, which occurs after Fas ligation. This effect is counteracted by a broad caspase inhibitor (zVAD-fmk). Fas-mediated cell death does not depend on CD8(+) T-cell infection, because it occurred in the presence of reverse transcriptase inhibitors. However, purified CD8(+) T cells are sensitive to Fas only in the presence of soluble CD4. Finally, we found that interleukin 7 (IL-7) increases Fas-mediated CD4(+) and CD8(+) T-cell death induced by HIV-1(LAI). Since high levels of IL-7 are a marker of poor prognosis during HIV infection, our data suggest that enhancement of Fas-mediated T-cell death by HIV-1(LAI) and IL-7 is one of the mechanisms involved in progression to AIDS.
Lelièvre
Jean-Daniel
JD
Inserm U421, Faculté de Médecine Henri Mondor, 8 rue du général Sarrail, 94010 Créteil cedex, France. lelievre@im3.inserm.fr
Petit
Frédéric
F
Arnoult
Damien
D
Ameisen
Jean-Claude
JC
Estaquier
Jérôme
J
D017209:Apoptosis / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D019014:fas Receptor / Q000378:metabolism
D007376:Interleukin-2; D015851:Interleukin-7; D019014:fas Receptor