CD27‐deficient mice show normal NK‐cell differentiation but impaired function upon stimulation

2011 ◽  
Vol 89 (7) ◽  
pp. 803-811 ◽  
Author(s):  
Veerle De Colvenaer ◽  
Sylvie Taveirne ◽  
Maarten Delforche ◽  
Magda De Smedt ◽  
Bart Vandekerckhove ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Nk Cell ◽  
Impaired Function ◽  
Nk Cell Differentiation ◽  
Deficient Mice

Impaired NK cell differentiation of blood-derived CD34+ progenitors from patients with myeloid metaplasia with myelofibrosis

2003 ◽  
Vol 106 (3) ◽  
pp. 201-212 ◽  
Author(s):  
Diane Briard ◽  
Danièle Brouty-Boyé ◽  
Julien Giron-Michel ◽  
Bruno Azzarone ◽  
Claude Jasmin ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Nk Cell ◽  
Myeloid Metaplasia ◽  
Nk Cell Differentiation

scholarly journals Evidence for discrete stages of human natural killer cell differentiation in vivo

2006 ◽  
Vol 203 (4) ◽  
pp. 1033-1043 ◽  
Author(s):  
Aharon G. Freud ◽  
Akihiko Yokohama ◽  
Brian Becknell ◽  
Melissa T. Lee ◽  
Hsiaoyin C. Mao ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Intermediate Stage ◽  
Cell Surface Expression ◽  
Lymphoid Tissues ◽  
Human Natural Killer Cell ◽  
Nk Cell Differentiation

Human natural killer (NK) cells originate from CD34(+) hematopoietic progenitor cells, but the discrete stages of NK cell differentiation in vivo have not been elucidated. We identify and functionally characterize, from human lymph nodes and tonsils, four NK cell developmental intermediates spanning the continuum of differentiation from a CD34(+) NK cell progenitor to a functionally mature NK cell. Analyses of each intermediate stage for CD34, CD117, and CD94 cell surface expression, lineage differentiation potentials, capacity for cytokine production and natural cytotoxicity, and ETS-1, GATA-3, and T-BET expression provide evidence for a new model of human NK cell differentiation in secondary lymphoid tissues.

scholarly journals Coordinated acquisition of inhibitory and activating receptors and functional properties by developing human natural killer cells

Blood ◽  
2006 ◽  
Vol 108 (12) ◽  
pp. 3824-3833 ◽  
Author(s):  
Bartosz Grzywacz ◽  
Nandini Kataria ◽  
Magdalena Sikora ◽  
Robert A. Oostendorp ◽  
Elaine A. Dzierzak ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Natural Killer ◽  
Cell Line ◽  
Nk Cell ◽  
Fetal Liver ◽  
Interferon Γ ◽  
Intermediate Phenotype ◽  
Interleukin 7 ◽  
Nk Cell Differentiation ◽  
And Function

AbstractThe stages of human natural killer (NK) cell differentiation are not well established. Culturing CD34+ progenitors with interleukin 7 (IL-7), IL-15, stem cell factor (SCF), FLT-3L, and murine fetal liver cell line (EL08.1D2), we identified 2 nonoverlapping subsets of differentiating CD56+ cells based on CD117 and CD94 (CD117highCD94– and CD117low/–CD94+ cells). Both populations expressed CD161 and NKp44, but differed with respect to NKp30, NKp46, NKG2A, NKG2C, NKG2D, CD8, CD16, and KIR. Only the CD117low/– CD94+ population displayed cytotoxicity and interferon-γ production. Both populations arose from a single CD34+CD38– Lin– cell and their percentages changed over time in a reciprocal fashion, with CD117highCD94– cells predominating early and decreasing due to an increase of the CD117low/–CD94+ population. These 2 subsets represent distinct stages of NKcell differentiation, since purified CD117high CD94– cells give rise to CD117low/–CD94+ cells. The stromal cell line (EL08.1D2) facilitated the transition from CD117highCD94– to CD117low/–CD94+ via an intermediate phenotype (CD117lowCD94low/–). EL08.1D2 also maintained the mature phenotype, preventing the reversion of CD117low/–CD94+ cells to the intermediate (CD117lowCD94low/–) phenotype. An analogous population of CD56+CD117highCD94– cells was found in cord blood. The identified stages of NK-cell differentiation provide evidence for coordinated acquisition of HLA-specific inhibitory receptors (ie, CD94/NKG2A) and function in developing human NK cells.

Eomes and T‐bet, a dynamic duo regulating NK cell differentiation

BioEssays ◽  
2022 ◽  
pp. 2100281
Author(s):  
Jiang Zhang ◽  
Noémi Rousseaux ◽  
Thierry Walzer
Keyword(s):  
Cell Differentiation ◽  
Nk Cell ◽  
Nk Cell Differentiation

scholarly journals The transcription factor ETS1 is an important regulator of human NK cell development and terminal differentiation

Blood ◽  
2020 ◽  
Author(s):  
Sylvie Taveirne ◽  
Sigrid Wahlen ◽  
Wouter Van Loocke ◽  
Laura Kiekens ◽  
Eva Persyn ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Cell Biology ◽  
Nk Cell ◽  
Embryonic Stem ◽  
Terminal Differentiation ◽  
Cell Development ◽  
Immune Defense ◽  
Nk Cell Differentiation ◽  
Important Regulator

Natural killer (NK) cells are important in the immune defense against tumor cells and pathogens, and regulate other immune cells by cytokine secretion. Whereas murine NK cell biology has been extensively studied, knowledge about transcriptional circuitries controlling human NK cell development and maturation is limited. By generating ETS1-deficient human embryonic stem cells (hESC) and by expressing the dominant-negative ETS1 p27 isoform in cord blood (CB) hematopoietic progenitor cells (HPCs), we show that the transcription factor ETS1 is critically required for human NK cell differentiation. Genome-wide transcriptome analysis determined by RNA-sequencing combined with chromatin immunoprecipitation-sequencing (ChIP-seq) analysis reveals that human ETS1 directly induces expression of key transcription factors that control NK cell differentiation, i.e. E4BP4, TXNIP, TBET, GATA3, HOBIT and BLIMP1. In addition, ETS1 regulates expression of genes involved in apoptosis and NK cell activation. Our study provides important molecular insights into the role of ETS1 as an important regulator of human NK cell development and terminal differentiation.

scholarly journals Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment

2010 ◽  
Vol 207 (10) ◽  
pp. 2065-2072 ◽  
Author(s):  
Nathalie T. Joncker ◽  
Nataliya Shifrin ◽  
Frédéric Delebecque ◽  
David H. Raulet
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Wild Type ◽  
Mhc I ◽  
Cell Functions ◽  
Histocompatibility Complex ◽  
Activating Receptors ◽  
Nk Cell Differentiation ◽  
Deficient Mice

Some mature natural killer (NK) cells cannot be inhibited by major histocompatibility complex (MHC) I molecules, either because they lack corresponding inhibitory receptors or because the host lacks the corresponding MHC I ligands for the receptors. Such NK cells nevertheless remain self-tolerant and exhibit a generalized hyporesponsiveness to stimulation through activating receptors. To address whether NK cell responsiveness is set only during the NK cell differentiation process, we transferred mature NK cells from wild-type (WT) to MHC I–deficient hosts or vice versa. Remarkably, mature responsive NK cells from WT mice became hyporesponsive after transfer to MHC I–deficient mice, whereas mature hyporesponsive NK cells from MHC I–deficient mice became responsive after transfer to WT mice. Altered responsiveness was evident among mature NK cells that had not divided in the recipient animals, indicating that the cells were mature before transfer and that alterations in activity did not require cell division. Furthermore, the percentages of NK cells expressing KLRG1, CD11b, CD27, and Ly49 receptors specific for H-2b were not markedly altered after transfer. Thus, the functional activity of mature NK cells can be reset when the cells are exposed to a changed MHC environment. These findings have important implications for how NK cell functions may be curtailed or enhanced in the context of disease.

Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education

Blood ◽  
2010 ◽  
Vol 116 (19) ◽  
pp. 3853-3864 ◽  
Author(s):  
Niklas K. Björkström ◽  
Peggy Riese ◽  
Frank Heuts ◽  
Sandra Andersson ◽  
Cyril Fauriat ◽  
...  
Keyword(s):  
Immune System ◽  
Cell Differentiation ◽  
Nk Cells ◽  
Nk Cell ◽  
Expression Patterns ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Phenotypic Properties ◽  
Hematopoietic Stem ◽  
Nk Cell Differentiation

Abstract Natural killer (NK) cells are lymphocytes of the innate immune system that, following differentiation from CD56bright to CD56dim cells, have been thought to retain fixed functional and phenotypic properties throughout their lifespan. In contrast to this notion, we here show that CD56dim NK cells continue to differentiate. During this process, they lose expression of NKG2A, sequentially acquire inhibitory killer cell inhibitory immunoglobulin-like receptors and CD57, change their expression patterns of homing molecules, and display a gradual decline in proliferative capacity. All cellular intermediates of this process are represented in varying proportions at steady state and appear, over time, during the reconstitution of the immune system, as demonstrated in humanized mice and in patients undergoing hematopoietic stem cell transplantation. CD56dim NK-cell differentiation, and the associated functional imprint, occurs independently of NK-cell education by interactions with self–human leukocyte antigen class I ligands and is an essential part of the formation of human NK-cell repertoires.

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