A NKp80-Based Identification Strategy Reveals that CD56(neg) NK Cells Are Not Completely Dysfunctional in Health and Disease

Natural killer (NK) cells are usually identified by the absence of other lineage markers, due to the lack of cell-surface-specific receptors. CD56(neg) NK cells, classically identified as CD56(neg)CD16+, are very scarce in the peripheral blood of healthy people but they expand in some pathological conditions. However, studies on CD56(neg) NK cells had revealed different results regarding the phenotype and functionality. This could be due to, among others, the unstable expression of CD16, which hinders CD56(neg) NK cells’ proper identification. Hence, we aim to determine an alternative surface marker to CD16 to better identify CD56(neg) NK cells. We have found that NKp80 is superior to CD16. Furthermore, we found differences between the functionality of CD56(neg)NKp80+ and CD56(neg)CD16+, suggesting that the effector functions of CD56(neg) NK cells are not as diminished as previously thought. We proposed NKp80 as a noteworthy marker to identify and accurately re-characterize human CD56(neg) NK cells.