Generation of mouse natural killer (NK) cell activity: Effect of interleukin-2 (IL-2) and interferon (IFN) on thein vivo development of natural killer cells from bone marrow (BM) progenitor cells

1986 ◽  
Vol 38 (4) ◽  
pp. 553-562 ◽  
Author(s):  
Carlo Riccardi ◽  
Antonio Giampietri ◽  
Graziella Migliorati ◽  
Lorenza Cannarile ◽  
Luciano D'Adamio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Progenitor Cells ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Killer Cells ◽  
Activity Effect

Influence of in vivo hypobaric hypoxia on function of lymphocytes, neutrocytes, natural killer cells, and cytokines

1993 ◽  
Vol 74 (3) ◽  
pp. 1100-1106 ◽  
Author(s):  
M. Klokker ◽  
A. Kharazmi ◽  
H. Galbo ◽  
I. Bygbjerg ◽  
B. K. Pedersen
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Cd8 Cells ◽  
The Absolute

We have investigated the effects of short-term hypoxia in vivo on the human cellular immune system. Seven young healthy volunteers were placed in a decompression chamber (380 Torr) for 20 min with or without supplemental O2. The leukocyte concentration increased during hypobaric conditions because of an increased concentration of lymphocytes. The absolute and relative concentration of CD16+ natural killer (NK) cells increased markedly during hypoxia and returned to pretest values after 2 h of recovery. The NK cell activity of blood mononuclear cells (BMNC, %lysis/fixed no. of BMNC) boosted with interferon-alpha, interleukin-2 (IL-2), and indomethacin rose in parallel with unboosted NK cell activity during hypoxia. The percentage of CD4+ and CD8+ cells declined during hypoxia, whereas the absolute concentration of both CD8+ cells and CD14+ monocytes increased. Although the BMNC composition varied, the proliferative responses of BMNC after stimulation with phytohemagglutinin, purified derivative of tuberculin, and IL-2 did not change significantly. The in vitro production of interleukin-1 beta and IL-2 in supernatants obtained after stimulation of BMNC with phytohemagglutinin or lipopolysaccharide was not affected. The chemiluminescence response of neutrocytes increased 2 h after hypoxia. It was concluded that acute hypoxia induced marked alterations in the immune system and that the NK cells are especially sensitive to the hypoxic stimulus.

Jagged2 promotes the development of natural killer cells and the establishment of functional natural killer cell lines

Blood ◽  
2005 ◽  
Vol 105 (9) ◽  
pp. 3521-3527 ◽  
Author(s):  
Sarah L. DeHart ◽  
Marc J. Heikens ◽  
Schickwann Tsai
Keyword(s):  
Natural Killer Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Lines ◽  
Nk Cell ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Lymphoid Cells ◽  
Killer Cells ◽  
Hematopoietic Stem

AbstractEmerging evidence indicates that Notch receptors and their ligands play important roles in the development of T cells and B cells. However, little is known about their possible roles in the development of other lymphoid cells. Here we demonstrate that Jagged2, a Notch ligand, stimulates the development of natural killer (NK) cells from Lin- Sca-1+ c-kit+ hematopoietic stem cells. Our culture system supports NK cell development for 2 to 3 months, often leading to the establishment of continuous NK cell lines. The prototype of such cell lines is designated as KIL. KIL depends on interleukin-7 for survival and proliferation and is NK1.1+ CD3- TCRαβ- TCRδγ- CD4- CD8- CD19- CD25+ CD43+ CD45+ CD49b- CD51+ CD94+ NKG2D+ Mac-1-/low B220- c-kit+ perforin I+ granzyme B+ Notch-1+, and cytotoxic. Like normal natural killer cells, the T-cell receptor-β loci of KIL remain in the germ-line configuration. In response to interleukin-2, KIL proliferates extensively (increasing cell number by approximately 1010-fold) and terminally differentiates into adherent, hypergranular NK cells. Our findings indicate that Jagged2 stimulates the development of natural killer cells and the KIL cell line preserves most properties of the normal NK precursors. As such, KIL provides a valuable model system for NK cell research.

scholarly journals Natural killer cells: origin, phenotype, function

2021 ◽  
Vol 23 (6) ◽  
pp. 1207-1228
Author(s):  
E. V. Tyshchuk ◽  
V. A. Mikhailova ◽  
S. A. Selkov ◽  
D. I. Sokolov
Keyword(s):  
Bone Marrow ◽  
Natural Killer Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Immunological Synapse ◽  
Nk Cell ◽  
Cell Receptor ◽  
Killer Cells ◽  
Activated State

Natural killer cells (NK) are innate immune lymphocytes produced in the bone marrow. Isolation of NK cells as a separate population of lymphocytes is related to discovery of their ability to induce the death of tumor cells without prior sensitization. In this review, an attempt was made to systematize the numerous data on the biology of NK cells presented in the literature. The authors consider the stages of NK cells` differentiation from a common lymphoid progenitor (CLP) in the bone marrow, describe two functionally different populations of mature NK cells – CD56brightCDl6- and CD56dimCD16+. In addition, the role of cytokines and chemokines in the development of NK cells is discussed. The review includes data on the spectrum of molecules expressed by NK cells: adhesion molecules (LFA-1, LFA-2, LFA-3; αMβ2, αXβ2, L-selectin, VLA-4, VLA-5; PECAM-1; CEACAM-1), cytokine receptors (IL-1R, IL-2ra, IL-2Rb/IL-2Rc, IL-6Rα, IL-7Ra, IL-8R, IL-10R, IL-12Rβ1, IL-15ra, IL-18R, IL-21ra, IFNGR2, TGFBR, c-Kit, CXCR1, CXCR3, CXCR4, CCR4, CCR5, CCR6, CCR7, IChemR23, CX3CR1), as well as receptors that regulate the activity of NK cells (LILRB1, LILRB2, LILRB4; KIR2DL1-5; KIR2DS1-5; KIR3DL1-3; KIR3DS1; NKG2A, NKG2C, NKG2D; Siglec7, Siglec9; CD16; NKRP-1; TIGIT; TACTILE; NKp30, NKp44, NKp46, NKp80; LAIR-1; PD-1; TIM-3; 2B4; TLR1-9). The authors also examine the mechanisms of implementing cytotoxic activity by NK cells, including cytotoxicity, via expression of MHC-I-specific receptors, CD16 Fc receptors, receptors and ligands of apoptosis (Fas-FasL and TRAIL-TRAILR) as well as other receptors. The review describes in detail the structure of immunological synapse between the NK cell and target cell, receptor interactions, and the role of the cytoskeleton in its formation. The data are summarized on the variants of exocytosis of lytic granules by NK cells, including complete or partial fusion of vesicles with the plasma membrane, exocytosis of vesicles containing perforin and FasL, and the formation of microvesicles containing granzyme B. The review also describes data on ability of NK cells to maintain activated state for a long time, as well as to maintain contact with several targets at the same time. In addition to the functions inherent in natural killers as cells of innate immunity, the authors point out their ability to exhibit the features of cells of adaptive immunity. In general, a variety of mechanisms that regulate the activity of NK cells may complement the specific functions of lymphocytes, thus making the immune system more efficient.

scholarly journals Differential Cytotoxicity of Cord Blood and Bone Marrow–Derived Natural Killer Cells

Blood ◽  
1998 ◽  
Vol 91 (1) ◽  
pp. 207-213
Author(s):  
Clair M. Gardiner ◽  
Anne O' Meara ◽  
Denis J. Reen
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Cytotoxic Activity ◽  
Natural Killer ◽  
Nk Cell ◽  
Granzyme B ◽  
Cell Activity ◽  
Lak Cells ◽  
Target Cells ◽  
Nk Cell Activity

Allogeneic cord blood is now being widely used as a source of stem cells for hematologic reconstitution after myeloablative therapy, with reported significantly lower levels of graft-versus-host disease (GVHD) compared with the use of allogeneic bone marrow (BM). This study was undertaken to investigate biologic aspects of natural killer (NK) cell activity, as recognized effector cells of the GVHD and graft-versus-leukemia (GVL) response, from cord blood and conventional BM. NK-cell activity levels of freshly isolated cells from cord blood and BM against K562 targets were comparable. Lymphokine activated killer (LAK) cells from both hematopoietic cell sources were compared for their ability to kill target cells by necrotic or apoptotic mechanisms using specific target cell lines. Cord blood cells had significantly higher necrosis-mediated cytotoxic activity against Daudi target cells compared with BM-derived cells. Cord blood LAK cells had relatively high levels of apoptotic-mediated cytotoxicity against YAC-1 target cells, whereas BM-derived LAK cells were unable to induce apoptosis in these cells. Interleukin-2 (IL-2) induced significant granzyme B activity in cord cells in contrast to BM cells, in which very little activity was measured. Western blotting confirmed these findings, with IL-2 inducing granzyme B protein expression in cord cells but not detectable levels in BM cells. BM cells had significantly lower cell surface expression of IL-2R and prolonged culture in IL-2 was only partially able to restore their deficient apoptotic cytotoxic activity. Thus, major differences exist between cord blood-derived and BM-derived mononuclear cells with respect to their NK-cell–associated cytotoxic behavior. This could have important implications for stem cell transplantation phenomena, because it suggests that cord blood may have increased potential for a GVL effect.

scholarly journals Differential Cytotoxicity of Cord Blood and Bone Marrow–Derived Natural Killer Cells

Blood ◽  
1998 ◽  
Vol 91 (1) ◽  
pp. 207-213 ◽  
Author(s):  
Clair M. Gardiner ◽  
Anne O' Meara ◽  
Denis J. Reen
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Cytotoxic Activity ◽  
Natural Killer ◽  
Nk Cell ◽  
Granzyme B ◽  
Cell Activity ◽  
Lak Cells ◽  
Target Cells ◽  
Nk Cell Activity

Abstract Allogeneic cord blood is now being widely used as a source of stem cells for hematologic reconstitution after myeloablative therapy, with reported significantly lower levels of graft-versus-host disease (GVHD) compared with the use of allogeneic bone marrow (BM). This study was undertaken to investigate biologic aspects of natural killer (NK) cell activity, as recognized effector cells of the GVHD and graft-versus-leukemia (GVL) response, from cord blood and conventional BM. NK-cell activity levels of freshly isolated cells from cord blood and BM against K562 targets were comparable. Lymphokine activated killer (LAK) cells from both hematopoietic cell sources were compared for their ability to kill target cells by necrotic or apoptotic mechanisms using specific target cell lines. Cord blood cells had significantly higher necrosis-mediated cytotoxic activity against Daudi target cells compared with BM-derived cells. Cord blood LAK cells had relatively high levels of apoptotic-mediated cytotoxicity against YAC-1 target cells, whereas BM-derived LAK cells were unable to induce apoptosis in these cells. Interleukin-2 (IL-2) induced significant granzyme B activity in cord cells in contrast to BM cells, in which very little activity was measured. Western blotting confirmed these findings, with IL-2 inducing granzyme B protein expression in cord cells but not detectable levels in BM cells. BM cells had significantly lower cell surface expression of IL-2R and prolonged culture in IL-2 was only partially able to restore their deficient apoptotic cytotoxic activity. Thus, major differences exist between cord blood-derived and BM-derived mononuclear cells with respect to their NK-cell–associated cytotoxic behavior. This could have important implications for stem cell transplantation phenomena, because it suggests that cord blood may have increased potential for a GVL effect.

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