Potential mechanisms of human natural killer cell expansion in vivo during low-dose IL-2 therapy

Todd A. Fehniger, Eric M. Bluman, Michelle M. Porter, Ewa Mrózek, Megan A. Cooper, Jeffrey B. VanDeusen, Stanley R. Frankel, Wendy Stock, Michael A. Caligiuri

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80 Scopus citations


The continuous, in vivo infusion of low-dose IL-2 selectively expands the absolute number of human natural killer (NK) cells after 4-6 weeks of therapy. The mechanism responsible for this expansion is unknown and was examined in this study. NK cells cultured at low concentrations of IL-2, comparable to those found during in vivo therapy, proliferate for 6 days and then exit the cell cycle. However, NK cells in vivo did not traverse the S/G2/M phase of the cell cycle during low-dose IL-2 therapy. Low concentrations of IL-2 delay programmed cell death of NK cells but have the same effect on resting T cells that do not expand in vivo. When CD34+ bone marrow hematopoietic progenitor cells are cultured for 21 days with low concentrations of IL-2, they differentiate into CD56+CD3- NK cells, not T cells. Thus, the selective expansion of human NK cells during continuous in vivo infusion of low-dose IL-2 likely results from enhanced NK-cell differentiation from bone marrow progenitors, combined with an IL-2-dependent delay in NK-cell death, rather than proliferation of mature NK cells in the periphery.

Original languageEnglish
Pages (from-to)117-124
Number of pages8
JournalJournal of Clinical Investigation
Issue number1
StatePublished - Jul 2000


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