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 Generation of human natural killer cells from immature progenitors does not require marrow stromal cells

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 841-846 ◽  
Author(s):  
MR Silva ◽  
R Hoffman ◽  
EF Srour ◽  
JL Ascensao
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Mononuclear Cells ◽  
Viral Infections ◽  
Nk Cell ◽  
Interleukin 2 ◽  
Peripheral Blood Mononuclear ◽  
Specific Lysis ◽  
Human Natural Killer Cells

Abstract Human natural killer (NK) cells comprise 10% to 15% of peripheral blood mononuclear cells and have an important role in immune responses against tumors, viral infections, and graft rejection. NK cells originate in bone marrow (BM), but their progenitors and lineage development have not been completely characterized. We studied the generation of NK cells from purified CD34+HLADR- and CD34+HLADR+ BM progenitors and the influence of various cytokines on their production. We show that CD3-CD56+ cytotoxic NK cells can develop from both progenitors populations when interleukin-2 (IL-2) is present in an in vitro suspension culture system containing IL-1 alpha and stem cell factor. Up to 83.8% and 98.6% CD3-CD56+ cells were detected in CD34+HLADR- and CD34+DR+ cultures, respectively, after 5 weeks of culture; significant numbers of NK cells were first detected after 2 weeks. Cytotoxic activity paralleled NK cell numbers; up to 70% specific lysis at an effector:target ratio of 10:1 was observed at 5 weeks. IL-7 also triggered development of CD3-CD56+ cells from these immature progenitors (up to 24% and 55% appeared in CD34+HLADR- and CD34+HLADR+ cultures, respectively). Our data suggest that BM stromas are not necessary for NK cell development and that IL-2 remains essential for this lineage development and differentiation.

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

UVB/PUVA- Induced Suppression of Human Natural Killer Activity Is Reduced by Superoxide Dismutase and/or Interleukin 2 In Vitro

1986 ◽  
Vol 86 (5) ◽  
pp. 519-522 ◽  
Author(s):  
Ken-ichi Toda ◽  
Yoshiki Miyachi ◽  
Naofumi Nesumi ◽  
Junji Konishi ◽  
Sadao Imamura
Keyword(s):  
Superoxide Dismutase ◽  
Natural Killer ◽  
Interleukin 2 ◽  
Natural Killer Activity ◽  
Killer Activity

Sulphasalazine and Derivatives, Natural Killer Activity and Ulcerative Colitis

1985 ◽  
Vol 69 (2) ◽  
pp. 177-184 ◽  
Author(s):  
P. R. Gibson ◽  
D. P. Jewell
Keyword(s):  
Ulcerative Colitis ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Nk Activity ◽  
Aminosalicylic Acid ◽  
Lipoxygenase Inhibitor ◽  
Peripheral Blood Mononuclear ◽  
Killer Activity

1. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA), sulphapyridine and azodisalicylic acid (ADS) in vitro on the natural killer (NK) activity of peripheral blood mononuclear cells (MNC) have been examined and compared with those of the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA) and the cyclooxygenase inhibitor, indomethacin. 2. Sulphasalazine, sulphapyridine and ADS inhibited NK activity with 50% inhibitory concentrations (IC50) of 0.7, 2.5 and 4.0 mmol/l respectively. The effect was rapidly reversible. In contrast, 5-ASA minimally inhibited NK activity at 50 mmol/l only. 3. NDGA potently inhibited NK activity (IC50 27 μmol/l) but this was only partly reversible in short term incubations. Indomethacin had no effect at concentrations less than those inhibiting cyclo-oxygenase activity (1-10 μmol/l) but potently and reversibly inhibited NK activity at or above 25 μmol/l. 4. The inhibitory effects observed were unlikely to be due to direct toxicity of effector cells as 5-ASA, sulphapyridine and ADS had no effect on the viability of peripheral blood MNC, whereas NDGA and indomethacin lysed MNC only at maximal concentrations tested. Though sulphasalazine produced MNC lysis at and above 1 mmol/l, the rapid reversibility of the inhibition of NK activity at 1 mmol/l suggested that lysis of NK cells contributed little to the suppressive effect at this concentration. 5. The disparity of the therapeutic efficacy and effects on NK activity of sulphasalazine and its derivatives in vitro may suggest that NK activity is not a major pathogenic mechanism in ulcerative colitis. Any inhibitory effect on cellular immune function of indomethacin does not necessarily reflect an effect of cyclo-oxygenase inhibition.

Age Related Natural Killer Activity of Peripheral Blood Lymphocytes from Healthy Subjects and Cancer Patients. A Comparative in Vitro Study with Interleukin-2

1994 ◽  
Vol 80 (3) ◽  
pp. 233-237 ◽  
Author(s):  
Abalokita Chakraborty ◽  
Nitya G. Chakraborty ◽  
Utpala Chattopadhyay
Keyword(s):  
Healthy Volunteers ◽  
Nk Cells ◽  
Cancer Patients ◽  
Interleukin 2 ◽  
The Elderly ◽  
Peripheral Blood Lymphocytes ◽  
Nk Activity ◽  
In Vitro Exposure ◽  
Lak Activity

Aims and Beckground Natural killer (NK) cell activity is known to be depressed in neoplastic diseases, and ageing influences the cytotoxicity of NK cells. However, very little information is available on the responsiveness of NK cells of cancer patients to the stimulating effects of interleukin-2 (IL-2) as a function of age. Methods We assessed in vitro IL-2 induced modulation of NK activity in peripheral blood lymphocytes (PBL) from 7 young (30-50 years) and 9 elderly (55-78 years) male patients with carcinoma of the oral cavity. In these patients generation of lyphokine activated killer (LAK) activity was also studied. NK and LAK activity of PBL were measured in 14 age and sex matched healthy volunteers as who served as conrols. Cytotoxicity of the NK and LAK cells was assayed against NK sensitive K562 and NK resistant Daudi cells in 4-h 51 Cr-release assays. Results NK activity in the cancer patients was significantly lower than that in healthy volunteers. In both groups the younger subjects had higher NK activity than the elderly ones. NK cells of both young and elderly healthy controls responded similarly to 24-hour in vitro exposure to human recombinant IL-2 (rIL-2, 100 u/ml) with highly increased cytotoxicity. Though there was significant enhancement of NK activity with rIL-2 in both young and elderly cancer patients, the rIL-2 induced NK cytotoxicity in the elderly patients was much lower than the basal level of NK activity of the age matched controls. Interestingly, LAK activity, generated by 3-7 days of in vitro exposure of PBL to rlL-2 was comparable in the cancer patients and healthy volunteers Conclusion The data suggest serious impairment of NK function in elderly patients with oral carcinoma. Generation of LAK activity with exogenous IL-2 could be an important modality of treatment in these patients.

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.

scholarly journals The generation of natural killer (NK) cells from NK precursor cells in rat long-term bone marrow cultures.

1990 ◽  
Vol 172 (1) ◽  
pp. 303-313 ◽  
Author(s):  
M R van den Brink ◽  
S S Boggs ◽  
R B Herberman ◽  
J C Hiserodt
Keyword(s):  
Bone Marrow ◽  
Nk Cells ◽  
Natural Killer ◽  
Interleukin 2 ◽  
Calf Serum ◽  
Precursor Cells ◽  
Killer Activity

In this report, we describe a novel long-term bone marrow culture (LTBMC) system to study the origin and generation of natural killer (NK) cells from NK precursors. Rat bone marrow was cultured for 4 wk in RPMI 1640 with 5% fetal calf serum and 2-mercaptoethanol to allow the formation of an adherent stromal cell layer containing NK precursor cells. After addition of interleukin 2 (IL-2), the LTBMC generated high numbers (up to 100-fold expansion in 7 d) of pure 3.2.3+ large granular lymphocytes with lytic activity against NK-sensitive and -resistant tumor targets, as well as antibody-dependent cellular cytotoxicity. NK activity in LTBMC could be detected 3 d after addition of as little as 1 U/ml rIL-2, whereas lymphokine-activated killer activity was found 5 d after addition of at least 10 U/ml rIL-2. In vivo depletion and in vitro complement lysis studies showed that the NK precursor cells in LTBMC did not express the NK-associated surface markers asialo GM1 or 3.2.3. We also found that LTBMC cells did not exhibit colony growth in granulocyte/macrophage or spleen colony-forming unit assays. The generation of NK cells from NK precursors required, in addition to IL-2, a second growth/maturation factor(s), which was present in the conditioned medium of the LTBMC. This LTBMC system provides a unique in vitro model to study the development of NK cells from precursor cells, the role of the bone marrow stromal microenvironment in this development, and the lineage relationship of NK cells to other hematopoietic cells.

scholarly journals Cytotoxic Activity of Peripheral Blood Mononuclear Leukocytes, Activated by Interleukin-2/β-Cyclodextrin Nanocomposition against Androgen Receptor-Negative Prostate Cancers

ISRN Oncology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-7
Author(s):  
Natalia Yu. Anisimova ◽  
Andrey V. Sosnov ◽  
Nadezhda E. Ustyuzhanina ◽  
Gianfranco Baronzio ◽  
Mikhail V. Kiselevsky
Keyword(s):  
Peripheral Blood ◽  
Water Solubility ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Natural Killer Activity ◽  
Mononuclear Leukocytes ◽  
Peripheral Blood Mononuclear ◽  
Killer Activity ◽  
K 562 Cells

Nanocomposition comprised of interleukin-2 in suboptimal noneffective concentration and β-cyclodextrin was studied in vitro. This preparation as well as interleukin-2 in optimal concentration was shown to increase natural killer activity to K-562 cells and cytotoxicity of activated peripheral blood mononuclear cells (PBMCs) against PC-3 and DU 145 cells. At the same time β-cyclodextrin or interleukin-2 in equimolar concentrations did not influence the spontaneous killer activity of PBMC. This combination of cyclodextrin + interleukin-2 led to the decrease of interleukin-2 effective concentration by an order. This phenomenon could be explained by cyclodextrins ability to promote the formation of nanoparticles with drugs, which results in enhancing their water solubility and bioavailability. Besides, interleukine-2/β-cyclodextrin nanocomposition as opposed to interleukin-2 alone led to increasing the number of not only lymphocytes, but also macrophages contained in activated PBMC population. Application of low concentration of interleukin-2 allowing for good clinical efficiency may significantly mitigate the side effects of the drug and enable to develop adoption of immunotherapy for patients with androgen-resistant prostate cancer.

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