Abstract

SummaryNatural killer (NK) cells are usually identified by the absence of other lineage markers, due to the lack of cell-surface-specific receptors. CD56neg NK cells, classically identified as CD56negCD16+, are very scarce in the peripheral blood of healthy people but they expand in some pathological conditions. However, studies on CD56neg 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 CD56neg NK cells’ proper identification. Hence, we aim to determine an alternative surface marker to CD16 to better identify CD56neg NK cells. We have found that NKp80 is superior to CD16. Furthermore, we found differences between the functionality of CD56negNKp80+ and CD56negCD16+, 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.

Highlights

  • Natural killer (NK) cells constitute an essential part of the innate immune system, and they are able to eliminate virus-infected and tumor cells without previous sensitization[1,2]

  • Studies with similar cohorts of patients differ in the frequency, functionality and phenotype of the CD56neg NK cell subset, which could be due to different CD56neg NK cell identification strategies[7,8,9,10]

  • The CD16 receptor has traditionally been used, in combination with CD56, to identify the three major subsets of NK cells, with CD56neg NK cells defined as CD56negCD16+

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Summary

Introduction

Natural killer (NK) cells constitute an essential part of the innate immune system, and they are able to eliminate virus-infected and tumor cells without previous sensitization[1,2]. Based on the expression of CD56 and CD16, and the absence of CD3, three NK cell subsets can be distinguish: CD56brightCD16+/-, CD56dimCD16+ and. The latter is very scarce in healthy donors, but it is expanded in chronic viral infections, such as HIV-1[3,4,5,6]. Studies with similar cohorts of patients differ in the frequency, functionality and phenotype of the CD56neg NK cell subset, which could be due to different CD56neg NK cell identification strategies[7,8,9,10]. The usage of this marker could lead to an inaccurate identification of CD56neg NK cells and inconsistent results

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