Interleukin-15 as an activator of natural killer cell-mediated antiviral response

Natural killer (NK) cells are large granular lymphocytes capable of efficie nt killing of virus-infected and tumor cells in a major histocompatibility complex-independent manner. The cytotoxic killing potential of NK cells can be modulated by a variety of factors, including cytokines such as interleu kin-12 (IL-12), IL-15, and interferon (IFN). IL-15 also plays an important role in NK cell development and survival. Killing of virally infected cells by NK cells is likely to represent an important antiviral defense mechanis m, especially during the early phase of infection when antigen-specific imm unity has yet to be generated. In the present work, we studied the potentia l of IL-15 to act as a modulator of NK cell-mediated antiviral defense. Our results clearly indicate that IL-15 can curtail infections by 3 human herp esviruses: Herpes simplex virus type 1, Epstein-Barr virus, and human herpe svirus 6. The antiviral activity of IL-15 is dose-, time-, and NK cell-depe ndent. IL-15-treated NK cells showed an increased killing potential against a variety of cells, including virus-infected target cells. Lastly, using h ighly purified cell population, we report that IL-15 triggers the synthesis of IFN-gamma from both CD4(+) and NK cells, which can act in both autocrin e and paracrine fashion to modulate MK cells cytotoxic potential. In conclu sion, IL-15 is a cytokine that can contribute to the establishment of an an tiviral state in 2 ways: first by increasing the killing ability of NK cell s and second by stimulating the synthesis and secretion of IFN. (C) 1999 by The American Society of Hematology.