Dataset Information

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

ABSTRACT: 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^negCD16+, 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^negNKp80+ and CD56^negCD16+, 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.

SUBMITTER: Orrantia A

PROVIDER: S-EPMC7334412 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A NKp80-Based Identification Strategy Reveals that CD56neg NK Cells Are Not Completely Dysfunctional in Health and Disease.

Orrantia Ane A Terrén Iñigo I Izquierdo-Lafuente Alicia A Alonso-Cabrera Juncal A JA Sandá Victor V Vitallé Joana J Moreno Santiago S Tasias María M Uranga Alasne A González Carmen C Mateos Juan J JJ García-Ruiz Juan C JC Zenarruzabeitia Olatz O Borrego Francisco F

iScience 20200620 7

Natural 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 ...[more]

PMID: 32622268

Similar Datasets

Project description:The differentiation of human induced pluripotent stem cells (hiPSCs) into T and natural killer (NK) lymphocytes opens novel possibilities for developmental studies of immune cells and in-vitro generation of cell therapy products. In particular, iPSC-derived NK cells gained interest in adoptive anti-cancer immunotherapies, since they enable generation of homogenous populations of NK cells with and without genetic engineering that can be grown at clinical scale. However, the phenotype of in-vitro generated NK cells is not well characterized. NK cells derive in the bone marrow and mature in secondary lymphoid tissues through distinct stages from CD56brightCD16- to CD56dimCD16+ NK cells that represents the most abandoned population in peripheral blood. In this study, we efficiently generated CD56+CD16+CD3- NK lymphocytes from hiPSC and characterized NK-cell development by surface expression of NK-lineage markers. Hematopoietic priming of hiPSC resulted in 31.9% to 57.4% CD34+CD45+ hematopoietic progenitor cells (HPC) that did not require enrichment for NK lymphocyte propagation. HPC were further differentiated into NK cells on OP9-DL1 feeder cells resulting in high purity of CD56brightCD16- and CD56brightCD16+ NK cells. The output of generated NK cells increased up to 40% when OP9-DL1 feeder cells were inactivated with mitomycine C. CD7 expression could be detected from the first week of differentiation indicating priming towards the lymphoid lineage. CD56brightCD16-/+ NK cells expressed high levels of DNAM-1, CD69, natural killer cell receptors NKG2A and NKG2D, and natural cytotoxicity receptors NKp46, NKp44, NKp30. Expression of NKp80 on 40% of NK cells, and a perforin+ and granzyme B+ phenotype confirmed differentiation up to stage 4b. Killer cell immunoglobulin-like receptor KIR2DL2/DL3 and KIR3DL1 were found on up to 3 and 10% of mature NK cells, respectively. NK cells were functional in terms of cytotoxicity, degranulation and antibody-dependent cell-mediated cytotoxicity.

Dataset Information

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

Publications

A NKp80-Based Identification Strategy Reveals that CD56<sup>neg</sup> NK Cells Are Not Completely Dysfunctional in Health and Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets