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Journal articles on the topic 'NK differentiation'

Author: Grafiati

Published: 1 February 2025

Last updated: 31 July 2025

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1

Kaur, Kawaljit, Angie Perez Celis та Anahid Jewett. "Natural Killer Cell-Secreted IFN-γ and TNF-α Mediated Differentiation in Lung Stem-like Tumors, Leading to the Susceptibility of the Tumors to Chemotherapeutic Drugs". Cells 14, № 2 (2025): 90. https://doi.org/10.3390/cells14020090.

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We demonstrate that natural killer (NK) cells induce a higher cytotoxicity against lung cancer stem-like cells (hA549) compared to differentiated lung cancer cell lines (H292). The supernatants from split-anergized NK cells (IL-2 and anti-CD16 mAb-treated NK cells) induced differentiation in hA549. Differentiated lung cancer cell line (H292) and NK cells differentiated hA549 expressed reduced NK cell-mediated cytotoxicity but expressed higher sensitivity to chemotherapeutic drugs. This finding validated our previous reports demonstrating that the levels of tumor killing by NK cells and by chem

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Persyn, Eva, Sigrid Wahlen, Laura Kiekens, et al. "TXNIP Promotes Human NK Cell Development but Is Dispensable for NK Cell Functionality." International Journal of Molecular Sciences 23, no. 19 (2022): 11345. http://dx.doi.org/10.3390/ijms231911345.

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The ability of natural killer (NK) cells to kill tumor cells without prior sensitization makes them a rising player in immunotherapy. Increased understanding of the development and functioning of NK cells will improve their clinical utilization. As opposed to murine NK cell development, human NK cell development is still less understood. Here, we studied the role of thioredoxin-interacting protein (TXNIP) in human NK cell differentiation by stable TXNIP knockdown or overexpression in cord blood hematopoietic stem cells, followed by in vitro NK cell differentiation. TXNIP overexpression only ha

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3

Vargas, Claudia L., Jennifer Poursine-Laurent, Liping Yang, and Wayne M. Yokoyama. "Development of thymic NK cells from double negative 1 thymocyte precursors." Blood 118, no. 13 (2011): 3570–78. http://dx.doi.org/10.1182/blood-2011-06-359679.

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Abstract The differentiation of natural killer (NK) cells and a subpopulation of NK cells which requires an intact thymus, that is, thymic NK cells, is poorly understood. Previous in vitro studies indicate that double negative (CD4−CD8−, DN) thymocytes can develop into cells with NK cell markers, but these cells have not been well characterized. Herein, we generated and characterized NK cells differentiating from thymic DN precursors. Sorted DN1 (CD44+CD25−) CD122−NK1.1− thymocytes from Rag1−/− mice were adoptively transferred into Rag1−/−Ly5.1 congenic mice. After intrathymic injection, donor

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4

Freud, Aharon G., Akihiko Yokohama, Brian Becknell, et al. "Evidence for discrete stages of human natural killer cell differentiation in vivo." Journal of Experimental Medicine 203, no. 4 (2006): 1033–43. http://dx.doi.org/10.1084/jem.20052507.

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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-

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Grzywacz, Bartosz, Nandini Kataria, Niketa Kataria, Bruce R. Blazar, Jeffrey S. Miller, and Michael R. Verneris. "Natural killer–cell differentiation by myeloid progenitors." Blood 117, no. 13 (2011): 3548–58. http://dx.doi.org/10.1182/blood-2010-04-281394.

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Abstract Because lymphoid progenitors can give rise to natural killer (NK) cells, NK ontogeny has been considered to be exclusively lymphoid. Here, we show that rare human CD34+ hematopoietic progenitors develop into NK cells in vitro in the presence of cytokines (interleukin-7, interleukin-15, stem cell factor, and fms-like tyrosine kinase-3 ligand). Adding hydrocortisone and stromal cells greatly increases the frequency of progenitor cells that give rise to NK cells through the recruitment of myeloid precursors, including common myeloid progenitors and granulocytic-monocytic precursors to th

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Vitale, Chiara. "Plasticity of NK-cell differentiation." Blood 117, no. 13 (2011): 3482–83. http://dx.doi.org/10.1182/blood-2011-01-327965.

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Lee, Jiwon, Suk Hyung Lee, Mira Jeong, and Inpyo Choi. "The effects of tumor necrosis factor-alpha on in vitro differentiation of natural killer cells (138.13)." Journal of Immunology 182, no. 1_Supplement (2009): 138.13. http://dx.doi.org/10.4049/jimmunol.182.supp.138.13.

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Abstract Natural killer (NK) cells are differentiated from hematopoietic stem cells (HSCs) in bone marrow. The differentiation of NK cells is regulated by various factors including soluble growth factors and transcription factors. Here, we demonstrated that tumor necrosis factor-α (TNF-α) is a positive regulator of NK cell differentiation. HSC-derived precursor NK (pNK) cells were further differentiated into mature NK (mNK) cells in the presence of IL-15 in vitro. The potential role of TNF-α on NK cell maturation was evaluated in the presence or absence of IL-15. TNF-α itself induced the expre

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8

Holmes, Tim D., Ram Vinay Pandey, Eric Y. Helm, et al. "The transcription factor Bcl11b promotes both canonical and adaptive NK cell differentiation." Science Immunology 6, no. 57 (2021): eabc9801. http://dx.doi.org/10.1126/sciimmunol.abc9801.

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Epigenetic landscapes can provide insight into regulation of gene expression and cellular diversity. Here, we examined the transcriptional and epigenetic profiles of seven human blood natural killer (NK) cell populations, including adaptive NK cells. The BCL11B gene, encoding a transcription factor (TF) essential for T cell development and function, was the most extensively regulated, with expression increasing throughout NK cell differentiation. Several Bcl11b-regulated genes associated with T cell signaling were specifically expressed in adaptive NK cell subsets. Regulatory networks revealed

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9

Sánchez, M. J., M. O. Muench, M. G. Roncarolo, L. L. Lanier, and J. H. Phillips. "Identification of a common T/natural killer cell progenitor in human fetal thymus." Journal of Experimental Medicine 180, no. 2 (1994): 569–76. http://dx.doi.org/10.1084/jem.180.2.569.

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The phenotypic similarities between natural killer (NK) and T cells have led to the hypothesis that these distinctive lymphocyte subsets may be developmentally related and thus may share a common progenitor (Lanier, L. L., H. Spits, and J. H. Phillips, 1992. Immunol. Today. 13:392; Rodewald, H.-R., P. Moingeon, J. L. Lurich, C. Dosiou, P. Lopez, and E. L. Reinherz. 1992. Cell. 69:139). In this report, we have investigated the potential of human CD34+ triple negative thymocytes ([TN] CD3-, CD4-, CD8-) to generate both T cells and NK cells in murine fetal thymic organ cultures (mFTOC) and in vit

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10

Cavazzana-Calvo, M., S. Hacein-Bey, G. de Saint Basile, et al. "Role of interleukin-2 (IL-2), IL-7, and IL-15 in natural killer cell differentiation from cord blood hematopoietic progenitor cells and from gamma c transduced severe combined immunodeficiency X1 bone marrow cells." Blood 88, no. 10 (1996): 3901–9. http://dx.doi.org/10.1182/blood.v88.10.3901.bloodjournal88103901.

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Natural killer (NK) cells are characterized by their ability to mediate spontaneous cytotoxicity against susceptible tumor cells and infected cells. They differentiate from hematopoietic progenitor cells. Patients with X-linked severe combined immunodeficiency (SCID X1) carry mutations in the gamma c cytokine receptor gene that result in lack of both T and NK cells. To assess the role of interleukin-2 (IL-2), IL-7, and IL-15 cytokines, which share gamma c receptor subunit, in NK cell differentiation, we have studied NK cell differentiation from cord blood CD34 (+) cells in the presence of eith

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11

Eisman, Shira, Batya Koenigsberg, Frederique van den Haak, et al. "The role of CXCR4-CXCL12 in the development and migration of human natural killer cells." Journal of Immunology 212, no. 1_Supplement (2024): 1152_4422. http://dx.doi.org/10.4049/jimmunol.212.supp.1152.4422.

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Abstract Natural killer (NK) cells play a critical role in controlling viral infection and malignancy and undergo differentiation from multipotent progenitors in secondary lymphoid tissue. Despite dependence on the microenvironment for differentiation, little is known about the cell-cell interactions that promote NK cell precursor trafficking and maturation in tissue. We have identified the chemokine receptor CXCR4 and its ligand CXCL12 as regulators of the cellular interactions between human NK cell precursors and stromal cells that support NK cell differentiation. Using in-vitro NK cell diff

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12

Soderquest, Katrina, Nick Powell, Carmelo Luci, et al. "Monocytes control natural killer cell differentiation to effector phenotypes." Blood 117, no. 17 (2011): 4511–18. http://dx.doi.org/10.1182/blood-2010-10-312264.

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Abstract Natural killer (NK) cells play a major role in immunologic surveillance of cancer. Whether NK-cell subsets have specific roles during antitumor responses and what the signals are that drive their terminal maturation remain unclear. Using an in vivo model of tumor immunity, we show here that CD11bhiCD27low NK cells migrate to the tumor site to reject major histocompatibility complex class I negative tumors, a response that is severely impaired in Txb21−/− mice. The phenotypical analysis of Txb21-deficient mice shows that, in the absence of Txb21, NK-cell differentiation is arrested spe

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Mikhailova, V. A., D. O. Bazhenov, K. L. Belyakova, S. A. Selkov, and D. I. Sokolov. "DIFFERENTIATION OF NK CELLS. A LOOK THROUGH THE PRISM OF TRANSCRIPTION FACTORS AND INTRACELLULAR MESSENGERS." Medical Immunology (Russia) 21, no. 1 (2019): 21–38. http://dx.doi.org/10.15789/1563-0625-2019-1-21-38.

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All lymphoid cells are referred to as an innate or adaptive immunity unit in terms of the mechanisms of performing immune reactions. The functional activity of natural killer (NK) cells is not associated with pre-activation processes resulting from contact with antigen, rearrangement of antigen-recognition receptor genes, and clonal proliferation. In this regard, NK cells are traditionally referred to as cells of innate immunity. Previously, it was believed that NK cells represent the only population of innate immunity lymphoid cells, but, more recently, there has been increasing evidence in t

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14

Risdon, G., TA Moore, V. Kumar, and M. Bennett. "Inhibition of murine natural killer cell differentiation by dehydroepiandrosterone." Blood 78, no. 9 (1991): 2387–91. http://dx.doi.org/10.1182/blood.v78.9.2387.2387.

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Abstract Dehydroepiandrosterone (DHEA) is a naturally occurring steroid. We have previously shown that dietary DHEA (0.45% wt/wt) inhibits murine lymphopoiesis but not myelopoiesis. To assess the effect of DHEA on stages of natural killer (NK) cell differentiation, lethally irradiated mice fed DHEA or not were infused with 10(6) or 20 x 10(6) syngeneic bone marrow cells (BMC) as a source of transplantable NK cell progenitors. The differentiation of progenitor cells to lytic NK cells was assessed by the ability to clear radiolabeled YAC-1 tumor cells from the lungs. DHEA-fed recipients of 10(6)

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15

Risdon, G., TA Moore, V. Kumar, and M. Bennett. "Inhibition of murine natural killer cell differentiation by dehydroepiandrosterone." Blood 78, no. 9 (1991): 2387–91. http://dx.doi.org/10.1182/blood.v78.9.2387.bloodjournal7892387.

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Dehydroepiandrosterone (DHEA) is a naturally occurring steroid. We have previously shown that dietary DHEA (0.45% wt/wt) inhibits murine lymphopoiesis but not myelopoiesis. To assess the effect of DHEA on stages of natural killer (NK) cell differentiation, lethally irradiated mice fed DHEA or not were infused with 10(6) or 20 x 10(6) syngeneic bone marrow cells (BMC) as a source of transplantable NK cell progenitors. The differentiation of progenitor cells to lytic NK cells was assessed by the ability to clear radiolabeled YAC-1 tumor cells from the lungs. DHEA-fed recipients of 10(6) or 20 x

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16

Montaldo, Elisa, Chiara Vitale, Francesca Cottalasso, et al. "Human NK cells at early stages of differentiation produce CXCL8 and express CD161 molecule that functions as an activating receptor." Blood 119, no. 17 (2012): 3987–96. http://dx.doi.org/10.1182/blood-2011-09-379693.

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Abstract Human natural killer (NK) cell development is a step-by-step process characterized by phenotypically identified stages. CD161 is a marker informative of the NK cell lineage commitment, whereas CD56, CD117, and CD94/NKG2A contribute to define discrete differentiation stages. In cells undergoing in vitro differentiation from CD34+ umbilical cord blood (UCB) progenitors, LFA-1 expression allowed to discriminate between immature noncytolytic CD161+CD56+LFA-1− and more differentiated cytolytic CD161+CD56+LFA-1+ NK cells. CD161+CD56+LFA-1− NK cells produce large amounts of CXCL8 after phorb

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17

Huyghe, Matthias, Christophe Desterke, Jusuf Imeri, et al. "Abstract 2778: Influence of the differentiation strategy on the phenotypic and genotypic features of iPSC derived NK cells." Cancer Research 84, no. 6_Supplement (2024): 2778. http://dx.doi.org/10.1158/1538-7445.am2024-2778.

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Abstract The iPSC-derived NK (iNK) cells offer new perspectives to produce large-scale of homogeneous immunotherapeutic cellular products and open the way towards manufacturing off-the-shelf cancer immunotherapies. Numerous strategies and protocols of differentiation of iPSCs toward NK lineage have been published in the last decade. Nevertheless, the embryological development of the NK cells and the impact of the differentiation strategy on the activity of the NK cells are still not clearly understood. Furthermore, very few studies have compared different NK differentiation strategies from iPS

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Lachota, Mieszko, Daniel Alfredo Palacios, Dennis Clement, et al. "Innate-like Chemokine Receptor Profile and Migratory Behaviour By Terminally Differentiated and Educated NK Cells." Blood 136, Supplement 1 (2020): 24–25. http://dx.doi.org/10.1182/blood-2020-140944.

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Natural Killer (NK) cells play an essential role in cancer surveillance and have a unique capability of spontaneous cytotoxicity against cancer cells. The human NK cell repertoire is functionally diversified through a tightly regulated differentiation process characterized by an early transition from CD56bright to CD56dim NK cells, followed by coordinated changes in expression of inhibitory receptors, including NKG2A and killer cell immunoglobulin-like receptors (KIR). The acquisition of self HLA class I binding KIRs during NK cell differentiation tunes the cytotoxic potential of NK cells in a

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Carotta, Sebastian, Swee Heng Milon Pang, Stephen L. Nutt, and Gabrielle T. Belz. "Identification of the earliest NK-cell precursor in the mouse BM." Blood 117, no. 20 (2011): 5449–52. http://dx.doi.org/10.1182/blood-2010-11-318956.

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Abstract Natural killer (NK) cells are generated in the bone marrow (BM) from lymphoid progenitors. Although several different maturation states of committed NK cells have been described, the initial stages of NK-cell differentiation from the common lymphoid progenitor are not well understood. Here we describe the identification of the earliest committed NK-cell precursors in the BM. These precursors, termed pre-pro NK cells, lack the expression of most canonical NK cell–specific surface markers but express the transcription factor inhibitor of DNA binding 2 and high levels of the IL-7 recepto

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Koo, G. C., F. J. Dumont, M. Tutt, J. Hackett, and V. Kumar. "The NK-1.1(-) mouse: a model to study differentiation of murine NK cells." Journal of Immunology 137, no. 12 (1986): 3742–47. http://dx.doi.org/10.4049/jimmunol.137.12.3742.

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Abstract The NK-1.1(-) mouse was constructed by weekly injections of monoclonal anti-NK-1.1 antibody from birth through adulthood. Spleen cells from these mice have decreased NK-1.1+ cells and null (Thy-1- and B220-) cells. Their splenic NK activity to YAC targets was low and was not enhanced by IFN-alpha or IFN-beta. Bone marrow (BM) of these NK-1.1(-) mice have normal precursors to NK cells: 1) NK activity could be generated from NK-1.1(-) BM cells cultured in rIL 2 for 5 to 6 days. These cultured BM cells expressed Qa-5, Thy-1, AsGm-1, and NK-1.1 antigens. The precursor cells of these BM cy

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Hidalgo, Laura, Víctor G. Martínez, Jaris Valencia, et al. "Expression of BMPRIA on human thymic NK cell precursors: role of BMP signaling in intrathymic NK cell development." Blood 119, no. 8 (2012): 1861–71. http://dx.doi.org/10.1182/blood-2011-07-370650.

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Abstract The bone morphogenetic protein (BMP) signaling pathway regulates survival, proliferation, and differentiation of several cell types in multiple tissues, including the thymus. Previous reports have shown that BMP signaling negatively regulates T-cell development. Here, we study the subpopulation of early human intrathymic progenitors expressing the type IA BMP receptor (BMPRIA) and provide evidence that CD34+CD1a−BMPRIA+ precursor cells mostly express surface cell markers and transcription factors typically associated with NK cell lineage. These CD34+ cells mostly differentiate into fu

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Giardina, SL, JD Coffman, HA Young, et al. "Association of the expression of an SR-cyclophilin with myeloid cell differentiation." Blood 87, no. 6 (1996): 2269–74. http://dx.doi.org/10.1182/blood.v87.6.2269.bloodjournal8762269.

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The role of a 150-kD SR-cyclophilin (NK-TR1) in monocyte differentiation was investigated. Using an antipeptide monoclonal antibody, we have detected NK-TR1 in human peripheral blood monocytes and HL-60 cells. Unstimulated monocytes showed a low intracellular level of NK-TR1 protein that increased over 3 days of lipopolysaccharide + interferon-gamma treatment, consistent with the kinetics of monocyte differentiation. Normal HL-60 cells also had a low level of NK-TR1 protein, and exposure to 1.25% dimethyl sulfoxide (DMSO) resulted in a marked transient increase in expression that returned to b

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Grzywacz, Bartosz J., Nandini Kataria, Jeffrey S. Miller, and Michael R. Verneris. "Stromal Cells Support a Myeloid Pathway of Human NK Cell Differentiation." Blood 110, no. 11 (2007): 1336. http://dx.doi.org/10.1182/blood.v110.11.1336.1336.

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Abstract Natural killer (NK) cells belong to the lymphocyte lineage; however a myeloid origin has been debated in the past based on nascent experimental evidence. We studied the in vitro development of human NK cells from UCB-derived CD34+ cells following culture with cytokines (IL15, IL7, SCF, FLT3L, IL3) on a murine fetal stromal cell line EL08.1D2 (Blood, 2006; 108: 3824–3833). We investigated the differential requirement of CD34+ subsets for stromal cell support. Limiting dilution experiments showed that CD34+ cells negative for phenotypic markers of NK commitment (CD7, CD161, integrin B7,

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Béziat, Vivien, Darragh Duffy, Stéphanie Nguyen Quoc, et al. "CD56brightCD16+NK Cells: A Functional Intermediate Stage of NK Cell Differentiation." Journal of Immunology 186, no. 12 (2011): 6753–61. http://dx.doi.org/10.4049/jimmunol.1100330.

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Kaur, Kawaljit, Anna Karolina Kozlowska, Paytsar Topchyan, et al. "Probiotic-Treated Super-Charged NK Cells Efficiently Clear Poorly Differentiated Pancreatic Tumors in Hu-BLT Mice." Cancers 12, no. 1 (2019): 63. http://dx.doi.org/10.3390/cancers12010063.

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Background and Aims: We have previously demonstrated that the stage of differentiation of tumors has profound effect on the function of NK cells, and that stem-like/poorly differentiated tumors were preferentially targeted by the NK cells. Therefore, in this study we determined the role of super-charged NK cells in immune mobilization, lysis, and differentiation of stem-like/undifferentiated tumors implanted in the pancreas of humanized-BLT (hu-BLT) mice fed with or without AJ2 probiotics. The phenotype, growth rate and metastatic potential of pancreatic tumors differentiated by the NK cells (

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Choi, Inpyo, Won Sam Kim, and Suk Ran Yoon. "Tanshinones increase natural killer cell maturation via activating p38 phosphorylation (P4464)." Journal of Immunology 190, no. 1_Supplement (2013): 52.49. http://dx.doi.org/10.4049/jimmunol.190.supp.52.49.

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Abstract The maturation of natural killer cells is regulated by various growth and nuclear transcription factors. Tanshinones, such as cryptotanshinone (CTS) and tanshinone IIA (TS), are the major lipophilic constituents extracted from the rhizome of Salvia miltiorrhiza Bunge. Here, we demonstrated that tanshinones are positive regulators for NK cell maturation. The tanshinones augmented the IL-15-induced expression of NK1.1 and CD122 in mature NK cells. Tanshinones also increased IFN-gamma production in NK cells in the presence of IL-15. They also induced the expression of several transcripti

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Qiao, Wenhua, Peng Dong, Hui Chen, and Jianmin Zhang. "Advances in Induced Pluripotent Stem Cell-Derived Natural Killer Cell Therapy." Cells 13, no. 23 (2024): 1976. http://dx.doi.org/10.3390/cells13231976.

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Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system capable of killing virus-infected cells and/or cancer cells. The commonly used NK cells for therapeutic applications include primary NK cells and immortalized NK cell lines. However, primary NK cell therapy faces limitations due to its restricted proliferation capacity and challenges in stable storage. Meanwhile, the immortalized NK-92 cell line requires irradiation prior to infusion, which reduces its cytotoxic activity, providing a ready-made alternative and overcoming these bottlenecks. Recent improvements in di

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Liu, Xuxiang, Jibin Zhang, Yunfei Shi, et al. "PRDM1 Promotes Primary Human Circulating CD56 dim NK-Cell Differentiation." Blood 142, Supplement 1 (2023): 1177. http://dx.doi.org/10.1182/blood-2023-180323.

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Background: Natural killer (NK) cells are innate lymphocytes that mount immune responses against viral infection and malignant cells. Circulating NK-cells can be generally divided into two groups, CD56 bright and CD56 dim, with the latter constituting ~90% of NK-cells in peripheral blood. While CD56 bright NK-cells are considered less mature and capable of producing more cytokines, CD56 dim population represents more differentiated cells with greater cytotoxicity. Transcription factor (TF) regulatory circuits were proposed for CD56 bright and CD56 dim NK-cells, indicating that TCF1/LEF1 and BA

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Mazzurana, Luca, Marianne Forkel, Anna Rao, et al. "Suppression of Aiolos and Ikaros expression by lenalidomide reduces human ILC3–ILC1/NK cell transdifferentiation." Journal of Immunology 202, no. 1_Supplement (2019): 187.10. http://dx.doi.org/10.4049/jimmunol.202.supp.187.10.

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Abstract The Ikaros family of transcription factors (TFs) are important regulators of lymphocyte function. However, their roles in human innate lymphoid cell (ILC) function remain unclear. Here, we found that Ikaros (IKZF1) is expressed by all ILC subsets, including NK cells, in blood, tonsil and gut, while Helios (IKZF2) is preferentially expressed by ILC3 in tonsil and gut. Aiolos (IKZF3) followed the expression pattern of T-bet and Eomes, being predominantly expressed by ILC1 and NK cells. Differentiation of IFN-γ-producing ILC1 and NK cells from ILC3 by IL-1β plus IL-12-stimulation was ass

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Sohlberg, Ebba, Aline Pfefferle, Eivind Heggernes Ask, et al. "Perturbed NK-cell homeostasis associated with disease severity in chronic neutropenia." Blood 139, no. 5 (2022): 704–16. http://dx.doi.org/10.1182/blood.2021013233.

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Abstract Neutrophils have been thought to play a critical role in terminal differentiation of NK cells. Whether this effect is direct or a consequence of global immune changes with effects on NK-cell homeostasis remains unknown. In this study, we used high-resolution flow and mass cytometry to examine NK-cell repertoires in 64 patients with neutropenia and 27 healthy age- and sex-matched donors. A subgroup of patients with chronic neutropenia showed severely disrupted NK-cell homeostasis manifesting as increased frequencies of CD56bright NK cells and a lack of mature CD56dim NK cells. These im

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Roeven, Mieke WH, Jeanette Cany, Frans Maas, et al. "The Aryl Hydrocarbon Receptor Antagonist Stemregenin 1 Stimulates Expression of NK Cell Related Transcription Factors, Thereby It Facilitates Generation of Highly Functional NK Cells in Vitro." Blood 124, no. 21 (2014): 3833. http://dx.doi.org/10.1182/blood.v124.21.3833.3833.

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Abstract Introduction Allogeneic stem cell transplantation (SCT) can be a curative treatment for hematological malignancies. The therapeutic effectiveness is attributed to the graft-versus-tumor (GVT) effect, mediated by alloreactive T cells and natural killer (NK) cells. Although T cells can induce a potent GVT effect, they can also induce graft-versus-host disease (GVHD), causing high morbidity and mortality. Interestingly, after non-myeloablative allogeneic SCT, early NK cell repopulation has been associated with decreased relapse rates, without increasing GVHD incidence, illustrating a pos

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Nabekura, Tsukasa, and Lewis L. Lanier. "Antigen-specific expansion and differentiation of natural killer cells by alloantigen stimulation." Journal of Experimental Medicine 211, no. 12 (2014): 2455–65. http://dx.doi.org/10.1084/jem.20140798.

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Natural killer (NK) cells provide important host defense against microbial pathogens and can generate a population of long-lived memory NK cells after infection or immunization. Here, we addressed whether NK cells can expand and differentiate after alloantigen stimulation, which may be important in hematopoietic stem cell and solid tissue transplantation. A subset of NK cell in C57BL/6 mice expresses the activating Ly49D receptor that is specific for H-2Dd. These Ly49D+ NK cells can preferentially expand and differentiate when challenged with allogeneic H-2Dd cells in the context of an inflamm

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Hackett, J., M. Bennett, and V. Kumar. "Origin and differentiation of natural killer cells. I. Characteristics of a transplantable NK cell precursor." Journal of Immunology 134, no. 6 (1985): 3731–38. http://dx.doi.org/10.4049/jimmunol.134.6.3731.

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Abstract To study the origin and differentiation of natural killer (NK) cells, we developed an assay for the transplantable precursor of NK(YAC-1) cells present in the bone marrow. Mice were depleted of endogenous NK(YAC-1) cells by injection of anti-asialo GM1 antibody, followed by lethal whole body irradiation. Normal syngeneic bone marrow cells were transplanted into such pretreated mice. Regeneration of NK(YAC-1) activity in the recipient mice was monitored by two different assays: the ability of spleen cells to lyse YAC-1 cells in vitro and the ability to clear i.v. injected, 125IUdR-labe

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Miller, JS, KA Alley, and P. McGlave. "Differentiation of natural killer (NK) cells from human primitive marrow progenitors in a stroma-based long-term culture system: identification of a CD34+7+ NK progenitor." Blood 83, no. 9 (1994): 2594–601. http://dx.doi.org/10.1182/blood.v83.9.2594.2594.

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Abstract We have recently described a marrow stroma-dependent long-term culture system that supports differentiation of CD34+ human marrow primitive progenitors into natural killer (NK) cells. We postulate that CD7 expression may be an early event in commitment of hematopoietic progenitors to the NK lineage. Here we compare the characteristics of CD34+7- and CD34+7+ marrow cells cultivated in the stroma-based NK culture system. These CD34+ populations were further compared with a marrow derived, more committed, CD34–7+ progenitor to emphasize the continuum of NK development and to highlight di

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Miller, JS, KA Alley, and P. McGlave. "Differentiation of natural killer (NK) cells from human primitive marrow progenitors in a stroma-based long-term culture system: identification of a CD34+7+ NK progenitor." Blood 83, no. 9 (1994): 2594–601. http://dx.doi.org/10.1182/blood.v83.9.2594.bloodjournal8392594.

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We have recently described a marrow stroma-dependent long-term culture system that supports differentiation of CD34+ human marrow primitive progenitors into natural killer (NK) cells. We postulate that CD7 expression may be an early event in commitment of hematopoietic progenitors to the NK lineage. Here we compare the characteristics of CD34+7- and CD34+7+ marrow cells cultivated in the stroma-based NK culture system. These CD34+ populations were further compared with a marrow derived, more committed, CD34–7+ progenitor to emphasize the continuum of NK development and to highlight differences

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Sullivan, Ryan P., Jeffrey W. Leong, Stephanie E. Schneider, et al. "Mir-15/16 Antagonizes Myb To Control Natural Killer Cell Differentiation and Maturation." Blood 122, no. 21 (2013): 17. http://dx.doi.org/10.1182/blood.v122.21.17.17.

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Abstract Introduction Natural Killer (NK) cells are lymphocytes that are important for early host defense against infectious pathogens and malignant transformation. NK cells differentiate from the CLP in the bone marrow, where they are identified by markers such as CD56 and NKp46 in humans, and NK1.1, CD122, and NKp46 in mice. NK cells further mature in the periphery, and this maturation is essential for NK cell function, as both NK cell cytotoxicity and IFN-g production are dependent upon maturation. NK cell maturation is distinguished by surface marker transitions, including CD56bright to CD

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Mitchell, Birgitta, Maritza Gonzalez, Jared Manning, and Gerald J. Spangrude. "Opposing Effects of Toll-Like Receptor Ligands and Ascorbic Acid On T and Natural Killer Cell Development From Lymphoid Progenitor Cells." Blood 114, no. 22 (2009): 1491. http://dx.doi.org/10.1182/blood.v114.22.1491.1491.

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Abstract Abstract 1491 Poster Board I-514 Introduction: A complete understanding of lymphocyte development, particularly factors driving T and natural killer (NK) cell differentiation from progenitor cells, remains an elusive goal in medicine. T and NK cells are key regulators in the defense against infections and malignancies and play a direct causative role in autoimmune diseases and graft-versus-host disease. The OP9-DL1 stromal line is an important tool in the in vitro study of lymphocyte development. Lymphocyte progenitors (KLS,Thy1.1-) harvested from adult murine bone marrow and seeded o

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Guimont-Desrochers, Fanny, Geneviève Boucher, Zhongjun Dong, Martine Dupuis, André Veillette, and Sylvie Lesage. "Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation." Blood 119, no. 19 (2012): 4349–57. http://dx.doi.org/10.1182/blood-2011-11-395954.

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Abstract The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relation of B220+ NK cells with regard to other NK-cell subsets. We surprisingly find that, after adoptive transfer, B220− NK cells did not acquire

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Koo, G. C., C. L. Manyak, J. Dasch, L. Ellingsworth, and L. D. Shultz. "Suppressive effects of monocytic cells and transforming growth factor-beta on natural killer cell differentiation in autoimmune viable motheaten mutant mice." Journal of Immunology 147, no. 4 (1991): 1194–200. http://dx.doi.org/10.4049/jimmunol.147.4.1194.

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Abstract Viable motheaten (mev) mice are homozygous for a recessive single gene mutation at chromosome 6. These mice develop numerous inflammatory and arthritic syndromes and exhibit abnormal B cell functions as well as lower T and NK cell activity. In this study, the differentiation of NK cells in mev mice was examined to elucidate the underlying basis for decreased NK activity. Although NK cells appear to be present in mev mice, their activity was demonstrable only when the spleen cells were enriched by nylon wool passage. Similarly bone marrow cells from these mice could be shown to contain

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Park, Il-Kyoo, Chiara Giovenzana, Tiffany L. Hughes, Jianhua Yu, Rossana Trotta, and Michael A. Caligiuri. "The Axl/Gas6 Pathway Is Required for Human Natural Killer Cell Development." Blood 110, no. 11 (2007): 2305. http://dx.doi.org/10.1182/blood.v110.11.2305.2305.

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Abstract Natural killer (NK) cells play an important role in host defense against microbial infection and tumors. Previous studies showed that IL-15 is essential for NK cell differentiation in vitro and in vivo. However the molecular mechanisms by which IL-15 is able to drive NK differentiation remain poorly understood. Here we show that blocking interaction between the receptor tyrosine kinase Axl and its ligands (Gas6 and protein S) by either soluble Axl/immunoglobulin Fc fusion protein (Axl-Fc) or warfarin, a vitamin K inhibitor, diminished the number and percentage of CD3−CD56+ NK cells di

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Sohlberg, Ebba, Aline Pfefferle, Eivind Heggernes Ask, et al. "Systems-Level Analysis of the Immune Repertoire in Neutropenia Reveal Arrested NK Cell Differentiation and Exhaustion." Blood 136, Supplement 1 (2020): 24–25. http://dx.doi.org/10.1182/blood-2020-141981.

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Neutrophils are innate cells that have been suggested to play a critical role in terminal differentiation of NK cells. Whether this is a direct effect or a consequence of global immune changes with effects on NK cell homeostasis remains unknown. Here, we used high-resolution flow and mass cytometry to examine NK cell repertoires in 64 neutropenic patients and 27 healthy age- and gender-matched controls. A subgroup of neutropenic patients had lower frequencies and absolute numbers of NK cells, yet increased frequencies of CD56bright among NK cells (Figure 1A-C). Moreover, their CD56dim compartm

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Huntington, Nicholas D., Nicolas Legrand, Nuno L. Alves, et al. "IL-15 trans-presentation promotes human NK cell development and differentiation in vivo." Journal of Experimental Medicine 206, no. 1 (2008): 25–34. http://dx.doi.org/10.1084/jem.20082013.

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The in vivo requirements for human natural killer (NK) cell development and differentiation into cytotoxic effectors expressing inhibitory receptors for self–major histocompatability complex class I (MHC-I; killer Ig-like receptors [KIRs]) remain undefined. Here, we dissect the role of interleukin (IL)-15 in human NK cell development using Rag2−/−γc−/− mice transplanted with human hematopoietic stem cells. Human NK cell reconstitution was intrinsically low in this model because of the poor reactivity to mouse IL-15. Although exogenous human IL-15 (hIL-15) alone made little improvement, IL-15 c

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Mailliard, Robbie B., Sean M. Alber, Hongmei Shen, et al. "IL-18–induced CD83+CCR7+ NK helper cells." Journal of Experimental Medicine 202, no. 7 (2005): 941–53. http://dx.doi.org/10.1084/jem.20050128.

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In addition to their cytotoxic activities, natural killer (NK) cells can have immunoregulatory functions. We describe a distinct “helper” differentiation pathway of human CD56+CD3− NK cells into CD56+/CD83+/CCR7+/CD25+ cells that display high migratory responsiveness to lymph node (LN)–associated chemokines, high ability to produce interferon-γ upon exposure to dendritic cell (DC)- or T helper (Th) cell–related signals, and pronounced abilities to promote interleukin (IL)-12p70 production in DCs and the development of Th1 responses. This helper pathway of NK cell differentiation, which is not

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Colucci, Francesco, Claire Soudais, Eleftheria Rosmaraki, Lesley Vanes, Victor L. J. Tybulewicz, and James P. Di Santo. "Dissecting NK Cell Development Using a Novel Alymphoid Mouse Model: Investigating the Role of the c-abl Proto-Oncogene in Murine NK Cell Differentiation." Journal of Immunology 162, no. 5 (1999): 2761–65. http://dx.doi.org/10.4049/jimmunol.162.5.2761.

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Abstract NK lymphocytes participate in both innate and adaptive immunity by their prompt secretion of cytokines including IFN-γ, which activates macrophages, and by their ability to lyse virally infected cells and tumor cells without prior sensitization. Although these characteristics of NK cells are well documented, little is known about the genetic program that orchestrates NK development or about the signaling pathways that trigger NK effector functions. By crossing NK-deficient common γ-chain (γc) and recombinase activating gene (RAG)-2 mutant mice, we have generated a novel alymphoid (B−,

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Colucci, Francesco, and James P. Di Santo. "The receptor tyrosine kinase c-kit provides a critical signal for survival, expansion, and maturation of mouse natural killer cells." Blood 95, no. 3 (2000): 984–91. http://dx.doi.org/10.1182/blood.v95.3.984.003k40_984_991.

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Fetal liver kinase ligands (flk2L/flt3L) and stem cell factor (SCF) have been shown to promote natural killer (NK) cell differentiation from hematopoietic stem cell (HSC) precursors in vitro. However, the contribution of signaling through the receptors for these growth factors for in vivo NK cell development remains ill-defined. We have analyzed the role of the SCF receptor c-kit in NK cell differentiation by reconstituting NK-deficient mice with fetal liver (FL) HSCs of c-kit−/− (W/W) mice. Although c-kit−/−NK cells were generated inW/W chimeras, they were reduced in number, contained a lower

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Yin, Jie, Jianmei W. Leavenworth, Yang Li, et al. "Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity." Proceedings of the National Academy of Sciences 112, no. 52 (2015): 15988–93. http://dx.doi.org/10.1073/pnas.1521740112.

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Changes of histone modification status at critical lineage-specifying gene loci in multipotent precursors can influence cell fate commitment. The contribution of these epigenetic mechanisms to natural killer (NK) cell lineage determination from common lymphoid precursors is not understood. Here we investigate the impact of histone methylation repressive marks (H3 Lys27 trimethylation; H3K27me3) on early NK cell differentiation. We demonstrate that selective loss of the histone-lysine N-methyltransferase Ezh2 (enhancer of zeste homolog 2) or inhibition of its enzymatic activity with small molec

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Yoshimori, Mayumi, Miwako Nishio, Ayaka Ohashi та ін. "Interferon-γ Produced by EBV-Positive Neoplastic NK-Cells Induces Differentiation into Macrophages and Procoagulant Activity of Monocytes, Which Leads to HLH". Cancers 13, № 20 (2021): 5097. http://dx.doi.org/10.3390/cancers13205097.

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Epstein–Barr virus (EBV)-positive T- or NK-cell neoplasms show progressive systemic inflammation and abnormal blood coagulation causing hemophagocytic lymphohistiocytosis (HLH). It was reported that inflammatory cytokines were produced and secreted by EBV-positive neoplastic T- or NK-cells. These cytokines can induce the differentiation of monocytes into macrophages leading to HLH. To clarify which products of EBV-positive neoplastic T- or NK-cells have effects on monocytes, we performed a co-culture assay of monocytes with the supernatants of EBV-positive T- or NK-cell lines. The expression o

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Chakraborty, Damayanti, M. A. Karim Rumi, and Michael Soares. "NK cells, hypoxia and trophoblast cell differentiation." Cell Cycle 11, no. 13 (2012): 2427–30. http://dx.doi.org/10.4161/cc.20542.

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49

Hackett, J., M. Tutt, M. Lipscomb, M. Bennett, G. Koo, and V. Kumar. "Origin and differentiation of natural killer cells. II. Functional and morphologic studies of purified NK-1.1+ cells." Journal of Immunology 136, no. 8 (1986): 3124–31. http://dx.doi.org/10.4049/jimmunol.136.8.3124.

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Abstract Cells bearing the NK-specific marker NK-1.1 were purified from mouse spleens by utilizing a monoclonal anti-NK-1.1 antibody and cell sorting. In normal adult mice, all of the splenic NK activity against YAC-1 cells was found in the NK-1.1+ fraction, whereas NK-1.1- cells were depleted of NK activity. The NK activity of sorted NK-1.1+ cells was enriched 15- to 30-fold over unfractionated spleen cells. Light and electron microscopic studies of purified NK-1.1+ cells showed a homogeneous population of cells, each containing one to four cytoplasmic granules. Mice whose bone marrow has bee

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Nakano, Saori, Akira Niwa, Yohko Kitagawa, Hidefumi Hiramatsu, and Megumu K. Saito. "IL-4 Acts at an Early Fate-Determining Junction in Hematopoiesis to Induce NK Cell Subsets Expressing Endogenous CD16." Blood 142, Supplement 1 (2023): 1. http://dx.doi.org/10.1182/blood-2023-188768.

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Human NK cells are known to contain subsets of CD56 +CD16 + and CD56 +CD16 - cells. The former directly attack target cells by an antibody-dependent cellular cytotoxicity (ADCC) various organs in the body, whereas the latter are mainly found in lymph nodes and activate inflammatory and immune responses by secreting IFNγ. However, despite their importance in the biological defence systems, whether and how these subsets emerge is not yet fully understood. In particular, several recent studies have challenged the conventional linear differentiation model which positioned CD56 +CD16 - cells as pro

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