Cytokine activation induces human memory-like NK cells

R Romee, SE Schneider, JW Leong… - Blood, The Journal …, 2012 - ashpublications.org
R Romee, SE Schneider, JW Leong, JM Chase, CR Keppel, RP Sullivan, MA Cooper
Blood, The Journal of the American Society of Hematology, 2012ashpublications.org
Natural killer (NK) cells are lymphocytes that play an important role in the immune response
to infection and malignancy. Recent studies in mice have shown that stimulation of NK cells
with cytokines or in the context of a viral infection results in memory-like properties. We
hypothesized that human NK cells exhibit such memory-like properties with an enhanced
recall response after cytokine preactivation. In the present study, we show that human NK
cells preactivated briefly with cytokine combinations including IL-12, IL-15, and IL-18 …
Abstract
Natural killer (NK) cells are lymphocytes that play an important role in the immune response to infection and malignancy. Recent studies in mice have shown that stimulation of NK cells with cytokines or in the context of a viral infection results in memory-like properties. We hypothesized that human NK cells exhibit such memory-like properties with an enhanced recall response after cytokine preactivation. In the present study, we show that human NK cells preactivated briefly with cytokine combinations including IL-12, IL-15, and IL-18 followed by a 7- to 21-day rest have enhanced IFN-γ production after restimulation with IL-12 + IL-15, IL-12 + IL-18, or K562 leukemia cells. This memory-like phenotype was retained in proliferating NK cells. In CD56dim NK cells, the memory-like IFN-γ response was correlated with the expression of CD94, NKG2A, NKG2C, and CD69 and a lack of CD57 and KIR. Therefore, human NK cells have functional memory-like properties after cytokine activation, which provides a novel rationale for integrating preactivation with combinations of IL-12, IL-15, and IL-18 into NK cell immunotherapy strategies.
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