Interleukin-15 protects from lethal apoptosis in vivo

S Bulfone-Paus, D Ungureanu, T Pohl, G Lindner, R Paus, R Rückert, H Krause, U Kunzendorf

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Interleukin-15 shares many biological activities with IL-2 and signals through the IL-2 receptor beta and gamma chains. However, IL-15 and IL-2 differ in their controls of expression and secretion, their range of target cells and their functional activities. These dissimilarities may include differential effects on apoptosis. For example, IL-2 induces or inhibits T-cell apoptosis in vitro, depending on T-cell activation, whereas IL-15 inhibits cytokine deprivation-induced apoptosis in activated T cells. Studying whether and how IL-15 modulates distinct apoptosis pathways, 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-IgG2b 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.

    Original languageEnglish
    Pages (from-to)1124-8
    Number of pages5
    JournalNature Medicine
    Volume3
    Issue number10
    Publication statusPublished - Oct 1997

    Keywords

    • Animals
    • Antigens, CD3
    • Antigens, CD95
    • Apoptosis
    • B-Lymphocytes
    • Cells, Cultured
    • DNA Fragmentation
    • Dexamethasone
    • Humans
    • Immunoglobulin G
    • Immunoglobulin M
    • Interleukin-15
    • Lymphocyte Activation
    • Mice
    • Palatine Tonsil
    • Recombinant Fusion Proteins
    • T-Lymphocytes
    • Transcription, Genetic

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