scholarly journals Diminished helper/suppressor lymphocyte ratios and natural killer activity in recipients of repeated blood transfusions

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 308-310 ◽  
Author(s):  
J Kaplan ◽  
S Sarnaik ◽  
J Gitlin ◽  
J Lusher
Keyword(s):  
Natural Killer ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Natural Killer Activity ◽  
Clotting Factor ◽  
Nk Activity ◽  
Killer Activity ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Clotting Factor Concentrates

Abstract Immunologic abnormalities qualitatively similar to those seen in acquired immunodeficiency syndrome (AIDS), including a low helper/suppressor lymphocyte ratio and low natural killer (NK) activity, have been observed in many hemophiliacs receiving clotting factor concentrates. To determine whether these changes also occur after repeated blood transfusion, we measured helper/suppressor (T4/T8) ratios and NK activity in four groups of test subjects: (A) 30 subjects with sickle cell anemia (SCA) receiving monthly transfusions, (B) 30 nontransfused sickle cell anemia subjects, (C) 87 individuals with hemophilia or severe von Willebrand's disease, and (D) 30 normal controls. Like the hemophiliacs, transfused SCA subjects had low T4/T8 ratios and low NK activity compared to controls. Nontransfused SCA subjects had normal values. These findings suggest that a modest decrease in T4/T8 ratio and NK activity may be part of the normal immune response to repeated transfusion.

scholarly journals Diminished helper/suppressor lymphocyte ratios and natural killer activity in recipients of repeated blood transfusions

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 308-310 ◽  
Author(s):  
J Kaplan ◽  
S Sarnaik ◽  
J Gitlin ◽  
J Lusher
Keyword(s):  
Natural Killer ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Natural Killer Activity ◽  
Clotting Factor ◽  
Nk Activity ◽  
Killer Activity ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Clotting Factor Concentrates

Immunologic abnormalities qualitatively similar to those seen in acquired immunodeficiency syndrome (AIDS), including a low helper/suppressor lymphocyte ratio and low natural killer (NK) activity, have been observed in many hemophiliacs receiving clotting factor concentrates. To determine whether these changes also occur after repeated blood transfusion, we measured helper/suppressor (T4/T8) ratios and NK activity in four groups of test subjects: (A) 30 subjects with sickle cell anemia (SCA) receiving monthly transfusions, (B) 30 nontransfused sickle cell anemia subjects, (C) 87 individuals with hemophilia or severe von Willebrand's disease, and (D) 30 normal controls. Like the hemophiliacs, transfused SCA subjects had low T4/T8 ratios and low NK activity compared to controls. Nontransfused SCA subjects had normal values. These findings suggest that a modest decrease in T4/T8 ratio and NK activity may be part of the normal immune response to repeated transfusion.

Impaired natural killer cytotoxicity in peripheral blood mononuclear cells in Graves' disease

1995 ◽  
Vol 132 (2) ◽  
pp. 175-180 ◽  
Author(s):  
Mónica Marazuela ◽  
Juan A Vargas ◽  
Melchor Alvarez-Mon ◽  
Fernando Albarrán ◽  
Tomás Lucas ◽  
...  
Keyword(s):  
Natural Killer ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Natural Killer Activity ◽  
Graves Disease ◽  
Nk Activity ◽  
Peripheral Blood Mononuclear ◽  
Killer Activity ◽  
Blood Mononuclear Cells

Marazuela M, Vargas JA, Alvarez-Mon M, Albarrán F, Lucas T, Durántez A. Impaired natural killer cytotoxicity in peripheral blood mononuclear cells in Graves' disease. Eur J Endocrinol 1995;132:175–80. ISSN 0804–4643 We studied the natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) in patients with Graves' disease (GD). Peripheral blood mononuclear cells from 20 untreated hyperthyroid patients with GD showed a significantly reduced NK activity against 51 Cr-labeled K562 cells (33.9 ± 15.9%), while in 32 euthyroid patients under antithyroid drug therapy, NK activity was similar to that of controls (46.9 ± 17.3 and 49.9 ± 20.2%, respectively). Furthermore, normalization of thyroid function with antithyroid drugs was associated with a significant increase and normalization of NK activity during the follow-up of nine GD patients (from 29.2 ± 17.9 to 48.1 ± 16.5%). This phenomenon could not be ascribed to a defective number of NK cells because the amounts of CD56 + and CD16 + cells in PBMC from both hyperthyroid and euthyroid GD patients were within normal ranges. Natural killer activity of PBMC from patients with toxic multinodular goiter was similar to that of normal controls (45 ± 12.8 to 49.9 ± 20%). No correlation was found between natural killer activity and serum levels of free thyroxine, TSH-inhibitory immunoglobulins, thyroidal antibodies to thryoglobulin and thyroidal microsomal antigen, dose or duration of antithyroid drug therapy. Natural killer activity from both controls and GD patients was enhanced in vitro by addition of recombinant interleukin 2 (IL-2), reaching control levels in hyperthyroid patients. These abnormalities were not associated with a defective IL-2 production by T cells, nor with a decreased IL-2R expression. We conclude that in untreated Graves' disease there is a decrease in NK cell activity in PBMC, probably dependent on the autoimmune process. Possible biological and clinical implications are discussed. Monica Marazuela, Hospital de la Princesa, c/Diego de Léon 62, Madrid 28006, Spain

Modulation of human natural killer activity by vasoactive intestinal peptide (VIP) family. VIP, glucagon and GHRF specifically inhibit NK activity

1992 ◽  
Vol 38 (1) ◽  
pp. 79-87 ◽  
Author(s):  
Maria Caterina Sirianni ◽  
Bruno Annibale ◽  
Fausto Tagliaferri ◽  
Stefano Fais ◽  
Severino De Luca ◽  
...  
Keyword(s):  
Natural Killer ◽  
Vasoactive Intestinal Peptide ◽  
Natural Killer Activity ◽  
Nk Activity ◽  
Killer Activity

scholarly journals Age-related expansion of functionally inefficient cells with markers of natural killer activity in Down's syndrome

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1263-1270
Author(s):  
A Cossarizza ◽  
C Ortolani ◽  
E Forti ◽  
G Montagnani ◽  
R Paganelli ◽  
...  
Keyword(s):  
Natural Killer ◽  
Lymphocyte Subsets ◽  
Down's Syndrome ◽  
Interleukin 2 ◽  
Down’S Syndrome ◽  
Natural Killer Activity ◽  
Nk Activity ◽  
Killer Activity ◽  
Age Related ◽  
Major Alteration

Peripheral blood lymphocyte subsets of two groups of patients affected by Down's syndrome (DS), ie, 28 children and nine adults of relatively advanced age (greater than 34 years), were investigated and compared with those of age- and sex-matched healthy controls (13 children and 20 adults). Particular attention was devoted to cells with markers of natural killer (NK) activity. Double- and triple-color cytofluorimetric analysis was used to better characterize the phenotypic features of the different subsets. Apart from a reduced number of T lymphocytes (CD3+) in DS children and of B lymphocytes (CD19+) in both DS groups, the major alteration we found was a marked age-related increase of the percentage of cells bearing markers associated with NK activity, such as CD16, CD56, and CD57. These DS cells were apparently severely defective as far as their function was concerned, because NK activity was significantly reduced in comparison with age-matched controls, but still capable of responding to cytokines such as interleukin-2, interferon-beta, and interferon-gamma, and to the modulation of lytic activity exerted by the anti-CD16 monoclonal antibody. On the whole, our data stress the importance of studying DS subjects of different ages to fully appreciate the immunologic derangement characteristic of this syndrome.

scholarly journals Impaired natural killer activity in patients with chronic lymphocytic leukemia is associated with a deficiency of azurophilic cytoplasmic granules in putative NK cells

Blood ◽  
1984 ◽  
Vol 63 (2) ◽  
pp. 305-309 ◽  
Author(s):  
NE Kay ◽  
JM Zarling
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Natural Killer Activity ◽  
Lymphocytic Leukemia ◽  
Nk Activity ◽  
Cell Surface Antigens ◽  
Killer Activity ◽  
Cytoplasmic Granules ◽  
Normal Individuals

This study was undertaken to gain further insight into the severely impaired natural killer (NK) activity we and others have previously observed in patients with chronic lymphocytic leukemia (CLL). Normal individuals' NK cells are large granular lymphocytes (LGL) that (A) bind to and lyse NK-sensitive cells, including K562, (B) express receptors for the Fc portion of IgG (FcR+ cells), and (C) express cell surface antigens reactive with monoclonal antibodies OKM1, 9.6, and OKT11A. We thus examined lymphocytes depleted of monocytes and B cells, from 6 CLL patients and 6 normal individuals, that were identified on the basis of binding to K562, expressing OKM1, or expressing receptors for the Fc portion of IgG. In the CLL patients studied, lymphocytes that bind to K562 cells, as well as OKM1+ cells isolated by fluorescence activated cell sorting, were morphologically similar to LGL of normal individuals, with the exception that more than 75% of the patientsx' cells were deficient in azurophilic cytoplasmic granules, which typify normal individuals LGL. Furthermore, although the percentages of the patients' FcR+ cells reactive with OKT11A, 9.6 and OKM1 were very similar to those of normals, the majority of the patients' FcR+ cells were deficient in azurophilic granules and lacked NK activity. These findings indicate that the impaired NK activity in CLL patients is associated with cells that are phenotypically and morphologically NK cells, but which lack azurophilic granules that are thought to play a role in NK-mediated lysis.

Defective NATURAL Killer ACTIVITY Improved by IL-2 Stimulation Independent of CD16 and NKG2D Receptors IN PATIENTS with THALASSEMIA MAJOR.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4746-4746
Author(s):  
Zeynep Karakas
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Natural Killer Activity ◽  
K562 Cells ◽  
Thalassemia Major ◽  
Nk Activity ◽  
Killer Activity ◽  
Medicine Department ◽  
Nk Cytotoxicity ◽  
Nkg2d Receptor

Abstract Abstract 4746 DEFECTIVE NATURAL KILLER ACTIVITY IMPROVED BY IL-2 STIMULATION INDEPENDENT OF CD16 AND NKG2D RECEPTORS IN PATIENTS WITH THALASSEMIA MAJOR Zeynep Karakaρ1,Belkýs Atasever2, Serap Erdem Kuruca3, Batu Erman2, Agaoglu Leyla1Istanbul Faculty of Medicine, Department of Pediatrics, Istanbul University, Istanbul, TurkeyFaculty of Engineering and Natural Sciences, Biological Sciences & Bioengineering Program, Sabanci University, Istanbul, Turkey3 Istanbul Faculty of Medicine, Department of Physiology, Istanbul University, Istanbul, Turkiye BACKGROUND Natural killer (NK) cells account for up to 15% of blood lymphocytes. Functional NK cells are found in the spleen. The function of NK cells is to recognize and kill virus infected cells and certain tumor cells. The mechanism of recognition is not fully understood, but it involves both activating and inhibitory receptors. CD 16 and NKG2D are receptors involved in two of the activation pathways of NK cells. NK cells use a variety of different mechanism to kill their targets. These include direct cell-cell signalling via surface molecules, and indirect signalling via cytokins. A decreased level of natural killer (NK) activity is one of the various immunological abnormalities in patients with thalassemia major. AIM This study aims to evaluate the relationship between NK cytotoxicity and CD 16 and NKG2D receptors, and effect of IL-2 stimulation in patients with thalassemia major. PATIENTS AND METHODS The study includes 26 patients with thalassemia major (TM) with age ranged 7-35 (median age was 18, 17 of them were female and 9 male), and sex and age matched 16 normal healthy subjects as controls. Fourteen of the patients were splenectomized. Patients regulary chelated with deferasirox (n:16), deferipron (n: 8) and desferroxamin (n: 2). NK cells were isolated from PBMC of subjects by using RosetteSep. Before and after the IL2 incubation; CD16, NKG2D receptors are examined in NK cells of both b-thalassemia major patients and controls by flow cytometry and we analyzed cytolytic function of NK cells against K562 cells. The cytotoxic activity of NK cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Ratios of NK cells /K562 cells (Efector:Target (E:T)) were 1:1, 10:1 and 20:1. RESULTS NK cytotoxicity was found to be lower at E:T ratios of 1:1 and 10:1 in patients with thalassemia major when compared to controls(p < 0.05). Patients with above 18 years old had significantly lower NK activity than below 18 years old. Sex, presence of splenectomy and chelation type did not effect on NK activity (p>0.05). NK cytotoxicity significantly increased by IL-2 stimulation in 26 patients at E:T ratio of 10:1 (p<0.05). But the increase was still less than the control. There was no significantly statistically difference between CD16 and NKG2D receptor levels compared with patients and controls. Patient's CD 16 receptor levels did not change after incubation with IL-2. NKG2D receptor levels of control NK cells significantly increased after IL-2 incubation (2021.66 / 1675.79/molecule, p<0.003). We detected significantly increased levels of NKG2D after IL-2 incubation in patients with splenectomy than patients without splenectomy (1834.80 / 901.41/molecule, p<0.005). CONCLUSION IL-2 may have potential therapeutic effect to improve the defective NK activity in patients with thalassaemia major. Increasing effect of IL-2 stimulation on NK activity may be independent than NKG2D receptor pattern. Defective NK cell functions can be partially restored by interleukin IL-2. This study was supported by Istanbul University Research Fund. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Compensatory effect of TNFalpha on low natural killer activity in the elderly.

2000 ◽  
Vol 47 (2) ◽  
pp. 301-311 ◽  
Author(s):  
J Myśliwska ◽  
E Bryl ◽  
P Trzonkowski ◽  
A Myśliwski
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Natural Killer Activity ◽  
The Elderly ◽  
Nk Activity ◽  
Killer Activity ◽  
Healthy Elderly

Regulatory effect of CD25, an activation antigen the alpha subunit of interleukin 2 receptor (IL2R) on the activity of natural killer (NK) cells was studied in fifty elderly (57-70 years old) and fifty young people (19-35 years old). Cytotoxic NK activity was assessed by 51Cr release assay, the levels of interleukin 2 (IL2) and tumour necrosis factors alpha (TNFalpha) were measured using bioassays and expression of CD16 and CD25 proteins by flow cytometry. Low NK activity in the elderly was associated with decline of full health, lowered serum concentration of IL2 and increased production of TNFalpha during NK reaction. Inhibition of TNFalpha activity by anti-TNF monoclonal antibody suppressed exclusively NK activity of low NK responders. Moreover, stimulation in vitro of blood mononuclear cells, with TNFalpha induced in the elderly low NK responders a significantly higher increase of the CD25 expression on the surface of NK cells as compared with that in the elderly high responders. Since the CD25 molecule constitutes a subunit of the high affinity receptor, binding IL2 to immunocompetent cells, its increased expression on NK cells of low NK responders would enable them to bind even low amounts of the endogenous IL2 available in this group of the elderly. Thus, an overproduction of TNFalpha seems to be a mechanism compensating, in the non-fully healthy elderly, for the decreased IL2 production, promoting efficient cytotoxic reaction.

scholarly journals Age-related expansion of functionally inefficient cells with markers of natural killer activity in Down's syndrome

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1263-1270 ◽  
Author(s):  
A Cossarizza ◽  
C Ortolani ◽  
E Forti ◽  
G Montagnani ◽  
R Paganelli ◽  
...  
Keyword(s):  
Natural Killer ◽  
Lymphocyte Subsets ◽  
Down's Syndrome ◽  
Interleukin 2 ◽  
Down’S Syndrome ◽  
Natural Killer Activity ◽  
Nk Activity ◽  
Killer Activity ◽  
Age Related ◽  
Major Alteration

Abstract Peripheral blood lymphocyte subsets of two groups of patients affected by Down's syndrome (DS), ie, 28 children and nine adults of relatively advanced age (greater than 34 years), were investigated and compared with those of age- and sex-matched healthy controls (13 children and 20 adults). Particular attention was devoted to cells with markers of natural killer (NK) activity. Double- and triple-color cytofluorimetric analysis was used to better characterize the phenotypic features of the different subsets. Apart from a reduced number of T lymphocytes (CD3+) in DS children and of B lymphocytes (CD19+) in both DS groups, the major alteration we found was a marked age-related increase of the percentage of cells bearing markers associated with NK activity, such as CD16, CD56, and CD57. These DS cells were apparently severely defective as far as their function was concerned, because NK activity was significantly reduced in comparison with age-matched controls, but still capable of responding to cytokines such as interleukin-2, interferon-beta, and interferon-gamma, and to the modulation of lytic activity exerted by the anti-CD16 monoclonal antibody. On the whole, our data stress the importance of studying DS subjects of different ages to fully appreciate the immunologic derangement characteristic of this syndrome.

scholarly journals Augmentation of mouse natural killer activity and induction of interferon by tumor cells in vivo.

1980 ◽  
Vol 151 (4) ◽  
pp. 781-789 ◽  
Author(s):  
J Y Djeu ◽  
K Y Huang ◽  
R B Herberman
Keyword(s):  
Natural Killer ◽  
Tumor Cells ◽  
Natural Killer Activity ◽  
Lymphocytic Choriomeningitis ◽  
Nk Activity ◽  
Killer Activity ◽  
Type C ◽  
D Cells ◽  
Species Specific

Conventional and nude mice inoculated with syngeneic or allogenic tumor cells developed a rapid rise in serum interferon (IF) levels, peaking within 24 h. Within the same period, natural killer (NK) activity was readily boosted in the spleen. Both activities usually declined at 3 d. Cells that lacked the ability to augment NK activity also failed to induce detectable levels of IF. The boosting of IF and NK functions did not appear to be a result of contamination of the tumor lines by viruses because inoculation of several type C viruses into normal mice had no effect, and other viruses, like lymphocytic choriomeningitis virus and influenza, elevated IF and NK levels with a significantly later kinetics, peaking 3-4 d. The IF induced by tumor cells was heat and acid labile, species specific, and appeared to be in the type II class, although it was susceptible to antisera against Newcastle disease virus-induced IF. These data suggest that an early, nonthymus-dependent consequence of tumor-cell recognition is the production of IF, which, in turn, activates NK cells to lyse the tumor cells.

scholarly journals Impaired natural killer activity in patients with chronic lymphocytic leukemia is associated with a deficiency of azurophilic cytoplasmic granules in putative NK cells

Blood ◽  
1984 ◽  
Vol 63 (2) ◽  
pp. 305-309 ◽  
Author(s):  
NE Kay ◽  
JM Zarling
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Nk Cells ◽  
Natural Killer ◽  
Natural Killer Activity ◽  
Lymphocytic Leukemia ◽  
Nk Activity ◽  
Cell Surface Antigens ◽  
Killer Activity ◽  
Cytoplasmic Granules ◽  
Normal Individuals

Abstract This study was undertaken to gain further insight into the severely impaired natural killer (NK) activity we and others have previously observed in patients with chronic lymphocytic leukemia (CLL). Normal individuals' NK cells are large granular lymphocytes (LGL) that (A) bind to and lyse NK-sensitive cells, including K562, (B) express receptors for the Fc portion of IgG (FcR+ cells), and (C) express cell surface antigens reactive with monoclonal antibodies OKM1, 9.6, and OKT11A. We thus examined lymphocytes depleted of monocytes and B cells, from 6 CLL patients and 6 normal individuals, that were identified on the basis of binding to K562, expressing OKM1, or expressing receptors for the Fc portion of IgG. In the CLL patients studied, lymphocytes that bind to K562 cells, as well as OKM1+ cells isolated by fluorescence activated cell sorting, were morphologically similar to LGL of normal individuals, with the exception that more than 75% of the patientsx' cells were deficient in azurophilic cytoplasmic granules, which typify normal individuals LGL. Furthermore, although the percentages of the patients' FcR+ cells reactive with OKT11A, 9.6 and OKM1 were very similar to those of normals, the majority of the patients' FcR+ cells were deficient in azurophilic granules and lacked NK activity. These findings indicate that the impaired NK activity in CLL patients is associated with cells that are phenotypically and morphologically NK cells, but which lack azurophilic granules that are thought to play a role in NK-mediated lysis.

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