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  • Title: Mechanisms of superior anti-tumor cytotoxic response of interleukin 15-induced lymphokine-activated killer cells.
    Author: Ozdemir O, Ravindranath Y, Savaşan S.
    Journal: J Immunother; 2005; 28(1):44-52. PubMed ID: 15614044.
    Abstract:
    Interleukin (IL) 15 is one of the main cytokines controlling cytotoxic lymphocyte survival and growth. Despite its receptor and functional similarity to IL-2, IL-15 affects a wider target cell population and utilizes different mechanisms in cell activation. The role of IL-15 in lymphokine-activated killer (LAK) cell generation in vitro and potential mechanisms of cytotoxicity compared with equivalent low concentration of IL-2 with or without mitogens (phytohemoglutinin (PHA) and anti-CD3 antibody) have been investigated in this study. IL-15 treatment resulted in moderate cell proliferation over 7 days, whereas IL-2 treatment was associated with decreased cell numbers. Unlike IL-2 in combination with mitogens, IL-15 caused increases in both cytotoxic T lymphocytes (CTL) and CD56 LAK cells, particularly cytokine-induced killer and cytolytic natural killer T-cell (CNK-T) subpopulations, which are known to be highly effective in cytotoxicity. IL-15 also increased overall perforin and tumor necrosis factor-alpha expression and more prominently in CTLs. Consequently, IL-15 resulted in superior cytotoxicity against two different NK-sensitive (human K-562 and murine YAC-1) and LAK-sensitive (human Daudi and Raji) cell lines compared with other cytokine combinations. There was also no contribution of mitogens to IL-2-induced cytotoxicity. In conclusion, IL-15 at the concentration of 10 ng/mL used in this study causes moderate proliferation and superior cytotoxicity of LAK cells in vitro that was associated with induction of a specific LAK cell subpopulation profile and related cellular killing mechanisms. These results are encouraging for potential use of IL-15 as part of immunotherapy.
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