CD56brightCD16+ NK Cells: A Functional Intermediate Stage of NK Cell Differentiation

Abstract

Human NK cells comprise two main subsets, CD56bright and CD56dim cells, which differ in function, phenotype, and tissue localization. To further dissect the differentiation from CD56bright to CD56dim cells, we performed ex vivo and in vitro experiments demonstrating that the CD56brightCD16+ cells are an intermediate stage of NK cell maturation. We observed that the maximal frequency of the CD56brightCD16+ subset among NK cells, following unrelated cord blood transplantation, occurs later than this of the CD56brightCD16− subset. We next performed an extensive phenotypic and functional analysis of CD56brightCD16+ cells in healthy donors, which displayed a phenotypic intermediary profile between CD56brightCD16− and CD56dimCD16+ NK cells. We also demonstrated that CD56brightCD16+ NK cells were fully able to kill target cells, both by Ab-dependent cell cytotoxicity (ADCC) and direct lysis, as compared with CD56brightCD16− cells. Importantly, in vitro differentiation experiments revealed that autologous T cells specifically encourage the differentiation from CD56brightCD16− to CD56brightCD16+ cells. Finally, further investigations performed in elderly patients clearly showed that both CD56brightCD16+ and CD56dimCD16+ mature subsets were substantially increased in older individuals, whereas the CD56brightCD16− precursor subset was decreased. Altogether, these data provide evidence that the CD56brightCD16+ NK cell subset is a functional intermediate between the CD56bright and CD56dim cells and is generated in the presence of autologous T CD3+ cells.

The evolution of cellular deficiency in GATA2 mutation

“…28 As previously reported, the most juvenile population of CD56 bright NK cells was absent in patients with GATA2 mutation, 21 supporting the model of NK differentiation from CD56 bright to CD56 dim populations ( Figure 5C-D). 29 Within the CD56 dim compartment, there was further evidence of skewing toward a more highly differentiated phenotype characterized by the loss of NKG2A and CD62L, and expression of killer-cell immunoglobulin-like receptors (KIR). 30 More detailed phenotyping of the CD8 1 T-cell compartment disclosed a reduction of naïve and central memory cells but an accumulation of CCR7 2 CD45RA 1 effector memory and CCR7 2 CD45RA 1 terminal effector populations ( Figure 5E).…”

Generation of natural killer cells from hematopoietic stem cells in vitro for immunotherapy

“…108 Likewise, Bjorkstrom et al recently proposed that CD56 dim cells continue to differentiate. During this process, NK cells lose the expression of NKG2A and later acquire KIRs and CD57 along with a change in their homing molecules expression pattern.…”

Human Lymphoid Tissues Harbor a Distinct CD69+CXCR6+ NK Cell Population

“…CD56 dim NK cells constitutively express high levels of perforin and granzyme B, resulting in efficient lysis of target cells without prior stimulation (14). In contrast, CD56 bright NK cells express perforin but require preactivation to exert cytotoxicity (8,9,11).…”

“…CD56 bright NK cells are considered the precursors of CD56 dim NK cells and represent 5-15% of NK cells in blood (10,11). CD56 bright NK cells express low levels of c-kit (CD117) and typically express the inhibitory receptor CD94/NKG2A (10)(11)(12).…”