A potential role for interleukin-15 in the regulation of human natural killer cell survival

William E. Carson, Todd A. Fehniger, Subrata Haldar, Kenneth Eckhert, Matthew J. Lindemann, Chun Fai Lai, Carlo M. Croce, Heinz Baumann, Michael A. Caligiuri

Research output: Contribution to journalArticlepeer-review

350 Scopus citations


Resting lymphocyte survival is dependent upon the expression of Bcl-2, yet the factors responsible for maintaining lymphocyte Bcl-2 protein expression in vivo are largely unknown. Natural killer (NK) cells are bone marrow-derived lymphocytes that constitutively express the β and common γ(c) subunits of the IL-2 receptor (R) as a heterodimer with intermediate affinity for IL-2. IL-15 also binds to IL-2Rβγ(c) and is much more abundant in normal tissues than IL-2. Mice that lack the IL-2 gene have NK cells, whereas mice and humans that lack IL-2Rγ(c) do not have NK cells. Further, treatment of mice with an antibody directed against IL-2Rβ results in a loss of the NK cell compartment. These data suggest that a cytokine other than IL- 2, which binds to IL-2Rβγ(c), is important for NK cell development and survival in vivo. In the current report, we show that the recently described IL-15Rα subunit cooperates with IL-2Rβγ(c) to transduce an intracellular signal at picomolar concentrations of lL-15. We demonstrate that resting human NK cells express lL-15Rα mRNA and further, that picomolar amounts of IL-15 can sustain NK cell survival for up to 8 d in the absence of serum. NK cell survival was not sustained by other monocyte-derived factors (i.e., TNF- α, IL-1β, IL-10, lL-12) nor by cytokines known to use γ(c) for signaling (i.e., IL-4, IL-7, IL-9, IL-13). One mechanism by which IL-15 promotes NK cell survival may involve the maintenance of Bcl-2 protein expression. Considering these functional properties of IL-15 and the fact that it is produced by bone marrow stromal cells and activated monocytes, we propose that IL-15 may function as an NK cell survival factor in vivo.

Original languageEnglish
Pages (from-to)937-943
Number of pages7
JournalJournal of Clinical Investigation
Issue number5
StatePublished - Mar 1 1997


  • Bcl-2
  • IL-15Rα
  • apoptosis
  • interleukin 15
  • natural killer cells


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