CD27 engagement by a soluble CD70 protein enhances non-cytolytic antiviral activity of CD56bright natural killer cells by IFN-γ secretion

•CD27 engagement by a soluble CD70 protein enhances IFN-γ secretion of NK cells.•CD27 engagement augments neither cytolytic activity nor proliferation of NK cells.•CD27 engagement enhances non-cytolytic antiviral activity of NK cells.

We investigated regulation of human NK cell function by CD27 engagement using a recombinant soluble CD70 protein. CD27 was preferentially expressed on CD56bright NK cells, and soluble CD70 protein bound to CD27+CD56bright NK cells. While soluble CD70 protein enhanced IFN-γ secretion by CD56bright NK cells in the presence of IL-12, it augmented neither cytolytic activity nor proliferation of NK cells. Thus, we next asked if soluble CD70 protein could be used to induce non-cytolytic antiviral activity of NK cells using an in vitro hepatitis C virus (HCV) infection system. Soluble CD70 protein stimulated NK cells to suppress HCV replication by enhancing NK cell IFN-γ secretion without killing infected cells. Taken together, we demonstrate that CD27 engagement by a soluble CD70 protein enhances non-cytolytic antiviral activity of CD56bright NK cells by IFN-γ secretion. Thus, this soluble CD70 protein may be useful for the treatment of viral infections such as HCV infection.