Interleukin-15 is a potent survival factor in the prevention of spontaneous but not CD95-induced apoptosis in CD4 and CD8 T lymphocytes of HIV-infected individuals. Correlation with its ability to increase BCL-2 expression.
IL-15 shares many biological properties with IL-2, a cytokine whose administration to HIV-infected individuals has been effective in enhancing depleted CD4 T lymphocyte numbers. The present study examined whether exogenous IL-15 could protect lymphocytes of HIV-infected individuals from spontaneous apoptosis, associated with growth factor deprivation, and CD95-induced apoptosis, which is believed to play a major role in T lymphocyte loss and HIV pathogenesis. Although IL-15, like IL-2, failed to inhibit CD95-induced lymphocyte apoptosis in vitro, IL-15 was found to act as a potent survival factor in the prevention of spontaneous apoptosis. The greater enhancement of lymphocyte survival, promoted by IL-15 as compared with IL-2 when used at an equivalent concentration, was associated with higher up-regulation of bcl-2 expression. In addition, IL-15 was more potent than IL-2 in stimulating lymphocyte proliferation. Despite the strong ability of IL-15 to promote both lymphocyte survival and proliferation, the increases in representation and total numbers of viable cells induced by IL-15 were not higher than those induced by IL-2. This appears to be associated with the greater ability of IL-15 to activate lymphocytes and increase their apoptosis-susceptibility. Therefore, lymphocyte loss occurring by growth factor deprivation in HIV infection may be potentially prevented by IL-15, although its benefits for survival need to be closely assessed against its ability to augment lymphocyte activation.
Naora
H
H
Unité d'Oncologie Virale and URA CNRS 1930, Departement SIDA et Retrovirus Institut Pasteur, 28 Rue du Dr. Roux, 75724 Paris, Cedex 15, France.
Gougeon
M L
ML
D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D019610:Cytoprotection / Q000187:drug effects / Q000276:immunology; D005047:Etoposide / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology* / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000187:drug effects*; D019014:fas Receptor / Q000276:immunology*
D019409:Interleukin-15; D019384:Nucleic Acid Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D005047:Etoposide