A NKp80-based identification strategy reveals that CD56neg 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 a cell surface specific marker. CD56neg NK cells, classically identified as CD56negCD16+ are known to be expanded in some pathological conditions. However, studies on CD56neg NK cells had revealed different results regarding the phenotype and functionality of these cells. This could be due to, among others, the unstable expression of CD16, which hinders CD56neg NK cells identification. Hence, we aim to determine an alternative surface marker to CD16 to better identify CD56neg NK cells. Using multiparametric flow cytometry, we have found that NKp80 is a good alternative to CD16 not only in healthy donors but also in HIV-1 infected subjects and multiple myeloma patients. Furthermore, we found differences between the functionality of CD56negNKp80+ and CD56negCD16+ NK cells both in healthy donors and patients, suggesting that the effector functions of CD56neg NK cells are not as diminished as previously thought. We proposed NKp80 as a noteworthy marker to identify and accurately re-characterize human CD56neg NK cells.