Bcl-xL is associated with the anti-apoptotic effect of IL-15 on the survival of CD56 dim natural killer cells

Abstract

Human NK cells can be distinguished into CD56 bright and CD56 dim subsets based on cell surface CD56 density. It has been shown that IL-2 and IL-15 have opposing effects on life and death of CD8 + T cells. However, the roles of IL-2 and IL-15 in regulating these two NK cell subsets remain elusive. In this study, we comparatively analyzed the effects of IL-2 and IL-15 on two NK cell subsets. IL-15 improved the proliferation and activation of CD56 dim NK cells in long-term cord blood mononuclear cell culture, but IL-2 only maintained the survival of CD56 bright NK cells. The percentage of CD56 +Annexin V + NK cells cultured with IL-15 was lower than that with IL-2; moreover, most of Annexin V + NK cells were primarily in the CD56 dim NK cells. IL-15 cultured NK cells expressed higher level of Bcl-xL than IL-2 cultured cells. Furthermore, IL-15 more strongly upregulated CD25 expression and better maintained the expression of IL-15Rα than IL-2. These results suggest that CD56 dim NK cells undergo apoptosis when cultured with IL-2, but IL-15 inhibits their apoptosis and Bcl-xL is associated with the anti-apoptotic effect of IL-15. So IL-15 played a crucial role in sustaining long-lasting functions of CD56 dim NK cells.