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Interleukin-15 protects from lethal apoptosis in vivo

Abstract

Interleukin-15 shares many biological activities with IL-2 and signals through the IL-2 receptor β and γ chains1–3. However, IL-15 and IL-2 differ in their controls of expression and secretion, their range of target cells and their functional activities3–7. These dissimilarities may include differential effects on apoptosis. For example, IL-2 induces or inhibits T-cell apoptosis in vitro, depending on T-cell activation8, whereas IL-15 inhibits cytokine deprivation-induced apoptosis in activated T cells9. Studying whether and how IL-15 modulates distinct apoptosis pathways10–12, we show here that apoptosis induced by anti-Fas, anti-CD3, dexamethasone, and/or anti-IgM in activated human T and B cells in vitro is inhibited by IL-15 in a manner dependent on RNA synthesis. In vivo, anti-Fas-induced lethal multisystem apoptosis in mice is suppressed by a novel IL-15–lgG2b fusion protein. Only IL-15, but not IL-2, completely protected from lethal hepatic failure. Thus, IL-15 is a potent, general inhibitor of apoptosis in vitro and in vivo with intriguing therapeutic potential.

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Bulfone-Paus, S., Ungureanu, D., Pohl, T. et al. Interleukin-15 protects from lethal apoptosis in vivo. Nat Med 3, 1124–1128 (1997). https://doi.org/10.1038/nm1097-1124

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