Cytotoxic functions and susceptibility to apoptosis of human CD56^bright NK cells differentiated in vitro from CD34⁺ hematopoietic progenitors

Abstract

Cytotoxic functions and susceptibility to apoptosis are crucial aspects of NK cells suitable to counter cancer after infusion in oncologic patients. To test the feasibility and the usefulness of infusing in vitro generated NK cells, these two features were investigated in NK cells developed in vitro from CD34 1 hematopoietic progenitors. Purified CD34 The NK functional activities and the end of NK cell responses are finely controlled by NK cell receptors (NKRs) with activatory and inhibitory functions. To this regard, NK cells express inhibitory receptors for MHC class I (MHC-I) molecules, the killer cell immunoglobulin (Ig)-like receptors (KIRs) and C-type lectin CD94-CD159a, which are able to block activatory signals. These latter signals are mainly triggered by CD16, natural cytotoxicity receptors (NCRs), NKG2D, and the leukocyte adhesion molecule DNAM-1 (CD226) (1,2). On the other hand, TNF ligand and receptor members are also involved both in NK cell-mediated cytotoxic function and in the control of NK cell response (3, reviewed in Ref. 4).Within the NK compartment, two phenotypically and functionally distinct NK subsets, CD56 bright and CD56 dim , have been described to represent either different stages of NK cell differentiation (Stage 4 and 5, respectively) or different subpopulations (similarly to CD4 and CD8 T cells, respectively) (2,5). In particular, CD56 dim / CD16 bright /CD117 neg NK cells are highly cytotoxic and preferentially express KIR inhibitory receptors, while the cytokine-producer CD56 bright NK cells are characterized by CD117 (c-kit) cytokine receptor and CD94-CD159a inhibitory receptor, although

Large granular lymphocytes are universally increased in human, macaque, and feline lentiviral infection

“…CD56 is expressed on human NK, iNKT cells, and NKT-like T cells (Khvedelidze et al, 2008; Peralbo et al, 2007; Zamai et al, 2012). CD56 expression was not found to be present on feline CD8lo + FAS + cells (data not shown).…”

The Memories of NK Cells: Innate-Adaptive Immune Intrinsic Crosstalk

“…CD56 bright NK cells show a high expression of CD56 and CD94/NKG2A antigens; functionally they have a high ability to produce immunoregulatory cytokines, in particular interferon- (IFN-) γ and tumor necrosis factor- (TNF-) α . CD56 bright and CD56 dim NK cells have been proposed to represent either different NK cell stages or distinct NK subpopulations [10–12]. Consistent with this latter hypothesis are the evidences of their different pathways of in vitro differentiation [12–14] and responses to stimuli.…”

“…CD56 bright and CD56 dim NK cells have been proposed to represent either different NK cell stages or distinct NK subpopulations [10–12]. Consistent with this latter hypothesis are the evidences of their different pathways of in vitro differentiation [12–14] and responses to stimuli. In fact, CD56 bright and CD56 dim NK cells are preferentially activated by NK activating cytokines or by cell targets, respectively [15, 16].…”

“…Of note, CD56 dim /CD16 bright /NKG2C + NK cells develop a specific adaptive feature [59–61] characterized by an enhanced response via CD16 stimulation, which suggests an improved cooperation of memory-like NK cells with B cells. In line with this hypothesis, the T cell cytokine IL-21 has been described to induce both the development of CD56 dim /CD16 bright NK cells from CD34 + hematopoietic progenitors [12, 13, 93] and the switching of Ig produced by B cell to IgG1 and IgG3 isotypes [94], for which Fc γ RIIIA receptor (CD16 of NK cells) displays a higher affinity [95]. Thus, through IL-21 secretion, T cells would be able to coordinate an ADCC response, inducing both an adequate isotype switching in B cells and an ADCC specialized NK cell subset.…”

Heterogeneity of Nk and NKT Lymphocyte Populations in Healthy Donors

“…В то же время некоторые NK-клетки спо-собны синтезировать IL-10, подавляющий им-мунный ответ [5,11,14]. CD56 -CD16 bright клетки также секретируют цитокины, но слабо способны продуцировать перфорин и пролиферировать [8,9,12,26,29]. Данные две субпопуляции облада-ют регуляторными функциями.…”