scholarly journals Patients with a deficiency of natural killer cell activity lack the VEP13-positive lymphocyte subpopulation

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 65-70 ◽  
Author(s):  
HW Ziegler-Heitbrock ◽  
H Rumpold ◽  
D Kraft ◽  
C Wagenpfeil ◽  
R Munker ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Target Cells ◽  
Nk Cell Activity

Many patients with B-type chronic lymphocytic leukemia (CLL) exhibit a profound defect in their natural killer (NK) cell activity, the basis of which is still obscure. Hence, we analyzed the NK cells from peripheral blood samples from 11 patients with CLL for phenotype and function, after removal of the leukemic cells with a monoclonal antibody (BA-1) plus complement. Phenotypic analysis of these nonleukemic cells with monoclonal antibodies (MoAbs) against NK cells revealed that the CLL patients had higher percentages of HNK-1-positive cells (23.5% compared to controls with 14.7%). In contrast, VEP13- positive cells were absent or low in seven patients (0.8% compared to controls with 11.2%) and normal in four patients (10.5%). When testing NK cell activities against K562 or MOLT 4 target cells, patients with no or minimal numbers of VEP13-positive cells were found to be deficient, while patients with normal percentages of VEP13-positive cells had NK cell activity comparable to controls. Isolation by fluorescence-activated cell sorter of HNK-1-positive cells from patients lacking VEP13-positive cells and NK cell activity indicated that the majority of the HNK-1-positive cells in these patients had the large granular lymphocyte morphology that is characteristic of NK cells. Thus, the deficiency of NK cell activity in CLL patients appears to result from the absence of cells carrying the VEP13 marker.

scholarly journals Patients with a deficiency of natural killer cell activity lack the VEP13-positive lymphocyte subpopulation

Blood ◽  
1985 ◽  
Vol 65 (1) ◽  
pp. 65-70 ◽  
Author(s):  
HW Ziegler-Heitbrock ◽  
H Rumpold ◽  
D Kraft ◽  
C Wagenpfeil ◽  
R Munker ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Target Cells ◽  
Nk Cell Activity

Abstract Many patients with B-type chronic lymphocytic leukemia (CLL) exhibit a profound defect in their natural killer (NK) cell activity, the basis of which is still obscure. Hence, we analyzed the NK cells from peripheral blood samples from 11 patients with CLL for phenotype and function, after removal of the leukemic cells with a monoclonal antibody (BA-1) plus complement. Phenotypic analysis of these nonleukemic cells with monoclonal antibodies (MoAbs) against NK cells revealed that the CLL patients had higher percentages of HNK-1-positive cells (23.5% compared to controls with 14.7%). In contrast, VEP13- positive cells were absent or low in seven patients (0.8% compared to controls with 11.2%) and normal in four patients (10.5%). When testing NK cell activities against K562 or MOLT 4 target cells, patients with no or minimal numbers of VEP13-positive cells were found to be deficient, while patients with normal percentages of VEP13-positive cells had NK cell activity comparable to controls. Isolation by fluorescence-activated cell sorter of HNK-1-positive cells from patients lacking VEP13-positive cells and NK cell activity indicated that the majority of the HNK-1-positive cells in these patients had the large granular lymphocyte morphology that is characteristic of NK cells. Thus, the deficiency of NK cell activity in CLL patients appears to result from the absence of cells carrying the VEP13 marker.

scholarly journals The role of cytokine in regulation of the natural killer cell activity

2008 ◽  
Vol 136 (7-8) ◽  
pp. 423-429 ◽  
Author(s):  
Vladimir Jurisic ◽  
Sladjana Stojacic-Djenic ◽  
Natasa Colovic ◽  
Gordana Konjevic
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Function ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Target Cells

Natural killer (NK) cells are characterized by a CD3-CD16+ CD56+ immunophenotype and have a central role in the innate immune system. They are defined by their capacity to kill certain tumor-target cells or virus infected cells without prior sensitization or MHC-restriction. The activity of the NK cells is determined by the balance between activation and inhibitory receptor molecules expressed on the surface of NK cells. However, several cytokines and chemokines can significantly modulate their activity, inducing increase of NK cell activity. Immunomodulation mediated by NK cells is very important mechanism in tumor immunity, as well as in other immunodepressions of the immune system. In this study, we summarize the role of several cytokines, including IFN, IL-1, IL-2, IL-4, IL-7, IL-12 and IL-17, on NK cell function. The NK cells, after activation, depending on cytokine environment, can differentiate into NK1 cells that produce Th1 cytokine type (IFN-?, IL-2, IL-12) or NK2 cells that produce Th2 type cytokines, enhance exocytosis and release of previously formed molecules from NK cells (granzyme, perforin). We also describe that the release of cytokines and mediators show local or distance effects, or induce apoptosis (mostly by secreted TNF-?) after binding appropriated killer cell receptors from TNF receptor superfamily.

Thermal stresses reduce natural killer cell cytotoxicity

1995 ◽  
Vol 79 (3) ◽  
pp. 732-737 ◽  
Author(s):  
S. J. Won ◽  
M. T. Lin
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Target Cell ◽  
Nk Cell ◽  
Cell Activity ◽  
Cortisol Concentration ◽  
Target Cells ◽  
Nk Cell Activity ◽  
Colonic Temperature ◽  
Effector Target

The effects of different ambient temperatures (Ta) on the splenic natural killer (NK) cell activity, effector-target cell conjugation activity, and NK cell numbers were assessed in male inbred C3H/HeNCrj mice (7–10 wk old). The splenic NK cytotoxic activities were examined in a 4-h 51Cr release assay in mouse spleen cells that were obtained 1, 2, 4, 8, or 16 days after exposure to Ta of 22, 4, or 35 degrees C. The percentage of conjugating lymphocytes was calculated by counting the number of single lymphocytes bound to single target cells per 400 effector cells. The numbers of NK cells were expressed by the percentage of 5E6-positive cells. The 5E6 identifies only a subset of NK cells. It was found that the splenic NK cell activity, the effector-target cell conjugation activity, or the NK cell number began to fall 1 day after cold (Ta 4 degrees C) or heat (Ta 35 degrees C) stress. After a 16-day period of either cold or heat exposure, the fall in the splenic NK cell activity, the effector-target cell conjugation activity, or the number of 5E6-positive subsets of NK cells was still evident. Compared with those of the control group (Ta 22 degrees C), the cold-stressed mice had higher adrenal cortisol concentration and lower colonic temperature, whereas the heat-stressed animals had higher adrenal cortisol concentration and higher colonic temperature during a 16-day period of thermal exposure. However, neither cold nor heat stress affected both the body weight gain and the spleen weight in our mice.

N-acetylcysteine does not affect the lymphocyte proliferation and natural killer cell activity responses to exercise

1998 ◽  
Vol 275 (4) ◽  
pp. R1227-R1231
Author(s):  
H. B. Nielsen ◽  
N. H. Secher ◽  
M. Kappel ◽  
B. K. Pedersen
Keyword(s):  
Natural Killer ◽  
Lymphocyte Proliferation ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Double Blind ◽  
Significant Difference ◽  
Ergometer Rowing

This study evaluated whether N-acetylcysteine (NAC) attenuates the reduced lymphocyte proliferation and natural killer (NK) cell activity responses to exercise in humans. Fourteen oarsmen were double-blind randomized to either NAC (6 g daily for 3 days) or placebo groups. During 6-min “all-out” ergometer rowing, the concentration of lymphocytes in the peripheral blood increased, with no significant difference between NAC and placebo as reflected in lymphocyte subsets: CD4+, CD8+, CD16+, and CD19+ cells. The phytohemagglutinin-stimulated lymphocyte proliferation decreased from 9,112 ± 2,865 to 5,851 ± 1,588 cpm ( P < 0.05), but it was not affected by NAC. During exercise, the NK cell activity was elevated from 17 ± 3 to 38 ± 4% and it decreased to 7 ± 1% below the resting value 2 h into recovery. Yet, when evaluated as lytic units per CD16+ cell, the NK cell activity decreased during and after exercise without a significant effect of NAC. We conclude that NAC does not attenuate the reduction in lymphocyte proliferation and NK cell activity associated with intense exercise.

scholarly journals Battle of Thermopylae: 300 Spartans (natural killer cells plus obinutuzumab) versus the immortal warriors (chronic lymphocytic leukemia cells) of Xerxes’ army

2019 ◽  
Vol 5 (10) ◽  
pp. FSO425
Author(s):  
Ricardo García-Muñoz ◽  
María-Josefa Nájera ◽  
Jesús Feliu ◽  
Judith Antón-Remírez ◽  
Enrique Ramalle-Gómara ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Killer Cell ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Lymphokine Activated Killer Cells ◽  
Killer Cells

Aim: To analyze the effects of subcutaneous or intravenous rituximab + lymphokine-activated killer cells, obinutuzumab or ibrutinib on natural killer (NK) cell levels in chronic lymphocytic leukemia and follicular lymphoma patients. Patients & methods: The distribution of peripheral blood NK cells of 31 patients was analyzed by flow cytometry. Results: We detected a decrease of NK cells in peripheral blood below normal range after obinutuzumab treatment. During maintenance treatment with subcutaneous rituximab, an NK cell reduction was less pronounced than after intravenous rituximab treatment, despite lymphokine-activated killer cell infusions. Conclusion: After one dose of obinutuzumab, each NK cell in peripheral blood destroys 25 leukemic cells.

scholarly journals IL-17 constrains natural killer cell activity by restraining IL-15–driven cell maturation via SOCS3

2019 ◽  
Vol 116 (35) ◽  
pp. 17409-17418 ◽  
Author(s):  
Xuefu Wang ◽  
Rui Sun ◽  
Xiaolei Hao ◽  
Zhe-Xiong Lian ◽  
Haiming Wei ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Cell Maturation ◽  
Dependent Manner ◽  
Deficient Mice

Increasing evidence demonstrates that IL-17A promotes tumorigenesis, metastasis, and viral infection. Natural killer (NK) cells are critical for defending against tumors and infections. However, the roles and mechanisms of IL-17A in regulating NK cell activity remain elusive. Herein, our study demonstrated that IL-17A constrained NK cell antitumor and antiviral activity by restraining NK cell maturation. It was observed that the development and metastasis of tumors were suppressed in IL-17A–deficient mice in the NK cell-dependent manner. In addition, the antiviral activity of NK cells was also improved in IL-17A–deficient mice. Mechanistically, ablation of IL-17A signaling promoted generation of terminally mature CD27−CD11b+ NK cells, whereas constitutive IL-17A signaling reduced terminally mature NK cells. Parabiosis or mixed bone marrow chimeras from Il17a−/−and wild-type (WT) mice could inhibit excessive generation of terminally mature NK cells induced by IL-17A deficiency. Furthermore, IL-17A desensitized NK cell responses to IL-15 and suppressed IL-15–induced phosphorylation of signal transducer and activator of transcription 5 (STAT5) via up-regulation of SOCS3, leading to down-regulation of Blimp-1. Therefore, IL-17A acts as the checkpoint during NK cell terminal maturation, which highlights potential interventions to defend against tumors and viral infections.

Suppressed Natural Killer Cell Activity in Patients with Silicone Breast Implants: Reversal upon Explantation

1994 ◽  
Vol 10 (3) ◽  
pp. 149-154 ◽  
Author(s):  
Andrew Campbell ◽  
Nachman Brautbar ◽  
Aristo Vojdani
Keyword(s):  
Natural Killer Cell ◽  
Natural Killer ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Breast Implants ◽  
Nk Cell Activity ◽  
Silicone Breast Implants ◽  
Killer Cell Activity

We have previously shown that natural killer (NK) cell activity is significantly suppressed in patients with silicone breast implants. These patients were symptomatic and the suppression of natural killer cell activity was associated with additional significant immunological abnormalities (Vojdani et al, 1992a). Our studies have recently been confirmed by Smith et al. (1994), who described natural killer cell activity suppression following exposure to silicone gel, and reversal upon removal of the gel. This study has been designed to evaluate natural killer cell activities in symptomatic women with silicone breast implants and again after explantation of the implants. Each patient served as her own control. Our findings show a marked significant increase in previously suppressed natural killer cell activity in 50% of the patients. In the other 50%, no change or suppressed NK activity was observed. These findings are compatible with recent studies in experimental animals, which show that administration of silicone reduces natural killer cell activity, and that this is reversible upon removal of the silicone. Since NK cells are important in the control of tumor cell growth, we propose here that patients with reduced NK cell activity are at a higher risk of developing cancer, a concept recently described in experimental animals (Potter et al., 1994; Salhon et al, 1994).

Effect of eccentric exercise on natural killer cell activity

1995 ◽  
Vol 78 (4) ◽  
pp. 1442-1446 ◽  
Author(s):  
J. Palmo ◽  
S. Asp ◽  
J. R. Daugaard ◽  
E. A. Richter ◽  
M. Klokker ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Eccentric Exercise ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Activity ◽  
Control Group ◽  
Systemic Effects ◽  
Nk Cell Activity ◽  
Blood Samples

The effect of eccentric one-legged exercise on natural killer (NK) cell activity was studied in eight healthy males. To distinguish between local and systemic effects, blood samples were collected from veins in the exercising leg and resting arm. However, the results did not significantly differ between the leg and arm. To eliminate diurnal variations, the results were compared with a control group that did not exercise but had blood samples collected at the same time points. In the exercising group, plasma creatine kinase increased progressively during and up to 4 days after exercise. The percentage of CD16+ NK cells increased during exercise, which was paralleled by an increase in the NK cell activity per fixed number of blood mononuclear cells. The NK cell activity on a per NK cell basis did not change. The percentage of CD3+, CD4+, CD8+, CD19+, and CD14+ cells did not change significantly during exercise. The present study thus showed that eccentric exercise with a relatively small muscle mass (1 quadriceps femoris muscle) causes systemic effects on NK cells. It is suggested that the increase in plasma epinephrine during eccentric exercise is responsible for the observed increase in the percentage of CD16+ cells.

scholarly journals Decrease of natural killer cell activity and monokine production in peripheral blood of patients treated with recombinant tumor necrosis factor

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 344-348 ◽  
Author(s):  
A Kist ◽  
AD Ho ◽  
U Rath ◽  
B Wiedenmann ◽  
A Bauer ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Natural Killer ◽  
Tumor Necrosis ◽  
Nk Cell ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Mononuclear Leukocytes ◽  
Nk Cell Activity ◽  
Necrosis Factor

Abstract Tumor necrosis factor (TNF), a protein predominantly produced by activated macrophages/monocytes, is presently available in recombinant, purified form for clinical trials. Intensive studies in many laboratories have shown that besides the tumorcytotoxic effects, TNF acts on a large array of different cells and has potent immunomodulatory activities. In a clinical phase I study, some immunologic functional parameters of blood cells from patients who received 24-hour infusions of recombinant human TNF (rhTNF) were analyzed. Natural killer (NK) cell activity, TNF production, interleukin-1 (IL-1) production and mitogen-induced proliferation were measured either in whole blood samples or in cultures of peripheral mononuclear leukocytes of the patients directly before and after rhTNF infusion. NK cell activity, TNF and IL-1 production capacity and proliferative responses to concanavalin A (Con A) were significantly reduced after rhTNF application. We conclude from these observations that rhTNF in vivo acts directly or indirectly on NK cells and monocytes by either inactivating their functional capacity or by absorbing the relevant cells to the endothelial cell layer, thus removing them from circulation.

Increase In NK Cell Lysis of Leukemic Blasts Due to Loss of Mismatched HLA Haplotype After Haplo-Identical Stem Cell Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2540-2540
Author(s):  
Yoshiyuki Takahashi ◽  
Itzel Bustos Villalobos ◽  
Sayoko Doisaki ◽  
Hideki Muramatsu ◽  
Akira Shimada ◽  
...  
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Cell Activity ◽  
Leukemic Cells ◽  
Target Cells ◽  
Chromosome 6 ◽  
Nk Cell Activity ◽  
Before And After ◽  
Hla Loss

Abstract Abstract 2540 Introduction: Hematopoietic stem cell transplantation (HSCT) from HLA haplo-identical family donors is promising as a therapy for patients with leukemia who are at high risk for relapse. The lower relapse rates and improved survival, especially for patients with acute myelogenous leukemia (AML) who have received HSCT from killer cell immunoglobulin-like receptor (KIR) ligand-mismatched donors, suggest that donor NK cells that are alloreactive against the recipient's cells cause graft-versus-leukemia effects. An Italian group and we identified genomic loss of the patient-specific HLA haplotype in leukemic cells after haplo-identical HSCT. Analysis using SNP arrays revealed that the HLA loss in 29 to 66% of relapsed patients after haplo-identical HSCT was caused by segmental uniparental disomy (UPD) of the HLA region on chromosome 6. This suggested that leukemic cells often escape immunosurveillance through the loss of the mismatched HLA haplotype via the UDP mechanism after haplo-identical HSCT (Vago et al. N Engl J Med. 2009, Villalobos, IB et al. Blood 2010). Since NK cell effector function is tightly regulated by inhibitory KIRs on NK cells that bind to MHC class I on target cells, the escape of leukemic cells from immune surveillance by losing a mismatched HLA antigen might enhance the cytotoxicity of NK cells towards target cells. We examined alterations in donor-derived alloreactive NK cell activity against leukemic blasts of AML patients who relapsed after HLA haplo-identical HSCT. Patients and methods: We enrolled three patients with AML, aged 2, 3 and 12 years, who relapsed after HLA haplo-identical HSCT with T cell depletion of rabbit ATG in vivo. Two patients had AML M7 and the other had M0. Only one donor was KIR ligand-mismatched. Engraftment was achieved in all three patients within 28 days. Relapse occurred 35, 372 and 445 days after HSCT. Mononuclear cells were obtained from both donors and patients before and after HSCT. The NK cells were purified using NK cell selection kits (DYNAL) and measured by conventional 51Cr release assays of leukemic blasts from the patients and the control cell line K562. The mismatched HLA expression between patients and donors on hematopoietic cells was monitored by flow cytometry using anti-HLA antibody (One Lambda). Results: The mean of NK cell killing of the patients' leukemic cells at the same effector target ratio of 10 was significantly higher in donors (50.3%) than in relapsed patients (9.7%). Monitoring of alloreactive NK cell activity after HSCT showed that donor-derived NK cell killing against the patients' leukemic cells gradually decreased in the KIR ligand-mismatched setting. Relapse was minimal but obvious according to HLA monitoring of hematopoietic cells on day 98, which was 7 days after alloreactive NK cell activity was diminished in the patients. Monitoring HLA expression after HSCT also revealed that one patient had leukemic blasts at relapse with loss of the patient's specific HLA haplotype caused by UDP of the HLA region on chromosome 6. Notably, primary leukemic blasts in this patient were not killed by the donor NK cells (2.3%), but leukemic blasts at relapse were efficiently killed (69.0%) after HLA loss of leukemic cells. On the other hand, killing of leukemic blasts at relapse by the patient's NK cells after transplantation was much less effective (19.0%) than that by donor NK cells, although they originated from the same donor (Figure). Because haplotype loss of HLA caused by UDP does not change the status of the KIR ligand in patients with homozygous HLA-Cw, we further examined the expression of ULBP1-3 that are ligands for the activating NK receptor, NKG2D, on leukemic blasts before and after HLA loss. We found upregulated ULBP-2 expression on leukemic cells after the loss of HLA. Conclusions: Donor NK cells efficiently killed patients' AML blasts at relapse but NK cell activity in patients against their own leukemic blasts was impaired after HSCT. These findings indicate a rationale for donor NK cell infusions after HLA haplo-identical HSCT to avoid decreasing NK cell alloreactivity and to prevent the escape of leukemic cells from allo-immune surveillance by donor cytotoxic T lymphocytes. Disclosures: No relevant conflicts of interest to declare.

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