EFFECTS OF HYPERTHERMIA IN VITRO ON NK ACTIVITY AND MTOC ORIENTATION

1991 ◽  
pp. 378
Author(s):  
H. YANG ◽  
W. LAUZON ◽  
I. LEMAIRE
Keyword(s):  
Nk Activity

scholarly journals Increased susceptibility of peripheral mononuclear cells of leukemic patients to HTLV-I infection in vitro

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1175-1181 ◽  
Author(s):  
G Graziani ◽  
D Pasqualetti ◽  
M Lopez ◽  
C D'Onofrio ◽  
AM Testi ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Healthy Controls ◽  
Nk Activity ◽  
Acute Leukemias ◽  
Normal Cells ◽  
Healthy Donors ◽  
Peripheral Mononuclear Cells ◽  
Cord Blood Lymphocytes ◽  
Increased Susceptibility

Abstract Peripheral mononuclear cells (MNC) collected from 12 healthy donors and 44 leukemic patients at various stages of the disease were tested for natural killer (NK) activity and for their susceptibility to HTLV-I infection in vitro, measured in terms of percentage of p19 positive cells. MNC from leukemic donors at any stage of leukemia (ie, onset or relapse, ON/REL; complete remission or off-therapy, CR/OT donors) were highly susceptible to HTLV-I infection. This was true for acute leukemias of lymphoblastic (ALL) or nonlymphoblastic (ANLL) type. MNC of ON/REL patients were more susceptible to HTLV-I than those of CR/OT donors. In addition, leukemic blasts were more rapidly infected (ie, within five to seven days) than the HTLV-I-susceptible normal cord- blood lymphocytes. However, the presence of circulating blasts was not essential to virus susceptibility, since CR/OT MNC, presumably free of leukemic blasts, were still more susceptible to HTLV-I than normal cells. Basal NK function of MNC from leukemic patients was significantly lower than that detectable in healthy controls. However, no correlation was found between susceptibility to HTLV-I infection and NK activity.

scholarly journals Direct evidence that natural killer cells in nonimmune spleen cell populations prevent tumor growth in vivo

1979 ◽  
Vol 149 (5) ◽  
pp. 1260-1264 ◽  
Author(s):  
M Kasai ◽  
JC Leclerc ◽  
L McVay-Boudreau ◽  
FW Shen ◽  
H Cantor
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Tumor Growth ◽  
Nk Cells ◽  
Spleen Cell ◽  
Cell Population ◽  
The Body ◽  
Nk Activity

Relatively large numbers of nonimmune spleen cells do not protect against the local growth of two lymphomas. However, this heterogeneous population of splenic lymphocytes contains a subset of cells that efficiently protects against in vivo tumor growth. This cell population (cell-surface phenotype Thyl.2(-)Ig(-)Ly5.1(+)) represents less than 5 percent of the spleen cell population and is responsible for in vitro NK-mediated lysis. Although these studies clearly and directly demonstrate that Ly5(+) NK cells selected from a heterogeneous lymphoid population from nonimmune mice can protect syngeneic mice against local in vivo growth of two different types of tumor cells (in contrast to other lymphocyte sets within the spleen), they do not directly bear upon the role of NK cells in immunosurveillance. They do indicate that highly enriched Ig(-)Thyl(-)Ly5(+) cells, which account for virtually all in vitro NK activity, can retard tumor growth in vivo. It is difficult to ascribe all anti-tumor surveillance activity to NK cells, because they probably do not recirculate freely throughout the various organ systems of the body. Perhaps NK ceils may play a role in prevention of neoplastic growth within discrete anatomic compartments where there is rapid differentiation of stem cells to mature progeny (e.g., bone marrow, spleen, and portions of the gastrointestinal tract)and may normally act to regulate the growth and differentiation of non-neoplastic stem cells. Long-term observation of chimeric mice repopulated with bone marrow from congenic or mutant donors expressing very low or very high NK activity may help to answer these questions.

scholarly journals Killer cells: a functional comparison between natural, immune T-cell and antibody-dependent in vitro systems.

1976 ◽  
Vol 143 (4) ◽  
pp. 772-780 ◽  
Author(s):  
R Kiessling ◽  
G Petranyi ◽  
K Kärre ◽  
M Jondal ◽  
D Tracey ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cell ◽  
Present Report ◽  
Leukemia Virus ◽  
Surface Characteristics ◽  
Functional Study ◽  
Nk Activity ◽  
Killer Cells ◽  
System Sensitivity

Previous reports have shown that spleen cells from nonimmune adult mice of certain strains do regularly kill Moloney leukemia virus-induced lymphomas in short-term 51Cr release assays. This naturally occuring killer (NK) cell had low adherent properties and had the morphological appearance of a lymphocyte. Still it lacked surface characteristics of mature T or B lymphocytes. In the present report a functional study was carried out, comparing in parallel the NK system, the T-cell killing across an H-2 barrier (anti-P815), and the antibody-dependent cell-mediated chicken red blood cell (CRBC) system. In contrast to the effector cells in the CRBC system, the NK cells were insensitive to erythrocyte antibody complement (EAC) rosette depletion and would pass through nylon wool columns. NK activity was not inhibited by the presence of heat-aggregated human or mouse gamma globulin, in contrast to the strong inhibition noted in the CRBC system. Sensitivity to trypsin pretreatment was noted in the NK system as well as in the immune P815 system, whereas the CRBC system was relatively trypsin resistant. Antitheta plus complement eliminated the anti-P815 activity, but did not touch the NK activity. The present results thus further distinguish the NK cell from cytotoxic T lymphocytes or from antibody-dependent killer cells.

In Vitro Modulation of Cellular Immunity with Antioxidants in Patients with Thalassemia Major.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3775-3775
Author(s):  
Belkis Atasever ◽  
Serap Erdem Kuruca ◽  
Zeynep Karakas ◽  
Leyla Agaoglu
Keyword(s):  
T Cells ◽  
Free Radicals ◽  
Vitamin E ◽  
Vitamin C ◽  
Iron Overload ◽  
Healthy Volunteers ◽  
Nk Cell ◽  
Cell Activity ◽  
Nk Activity

Abstract Immunological disturbances have been reported in thalassemia and the possibility has been raised that these may be consequences of blood transfusion and iron overload. These disturbances are augmentation of the number of supressor T cells (CD8), decreased number and activity of helper T cells (CD4) and impaired activity of NK (natural killer) cells. Iron overload causes toxic tissue changes through the release of free radicals and induces oxidative stress. According to Fenton and Haber-Weiss reactions, iron plays a catalytic role occuring hydroxyl radicals (OH*) which are very reactive free radicals. Antioxidants, like vitamin E, vitamin C and selenium, may modulate oxidative damage. In the present study; firstly, normal lymphocytes mitogen responses and NK activity were investigated by colorimetric MTT test in 26 thalassemia patients and 10 healthy volunteers as control. Secondly, lymphocytes were incubated with vitamin E ( 150, 50, 15 mg/ml), vitamin C (200, 100, 20mg/ml) and selenium (10−5, 10−6, 10−7 M). Finally, lymphocytes mitogen responses and NK activity are investigated. The results were statistically analyzed comparing with controls and healthy volunteers. It was found decreased NK activity of thalassemia patients in comparison with healthy volunteers. The concentration of 10−7 M of selenium enhanced NK activity at the E:T (effector/target) ratio of 50:1 The concentration of 200 mg/ml of vitamin C enhanced NK activity at the E:T ratio of 10:1, 25:1 and 50:1. However, vitamin E decreased NK activity of both thalassemia patients and healhty volunteers. The concentration of 50 mg/ml vitamin E decreased NK activity at the E:T ratio of 5:1 in thalassemia patients and the concentration of 15 mg/ml of vitamin E decreased NK activity at the E:T ratio of 5:1 in healhty volunteers. It was not found any differences between thalassemia patients and healthy volunteers in lymphocytes mitogen responses. The concentration of 200 mg/ml of vitamin C decreased lymphocytes mitogen response against PHA. In conclusion, we suggest that vitamin C and selenium supplementation are required in patients with thalassemia for augmentation of NK cell activity.

Co-Transfusion of Donor NK Cells in Haploidentical Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2907-2907
Author(s):  
Peter J. Lang ◽  
Matthias Pfeiffer ◽  
Heiko-Manuel Teltschik ◽  
Ingo Mueller ◽  
Tobias Feuchtinger ◽  
...  
Keyword(s):  
Nk Cells ◽  
Relapse Rate ◽  
Peripheral Blood ◽  
Nk Cell ◽  
Ex Vivo ◽  
Thymidine Uptake ◽  
Nk Activity ◽  
Specific Lysis ◽  
The Mean

Abstract 39 pedatric patients with acute leukemias (ALL (n=19), AML (n=14) and MDS (n=6)) received T and B cell depleted grafts from full haplotype mismatched related donors. Depletion of the G-CSF stimulated leukapheresis products was carried out with CD3/CD19 coated magnetic microbeads and the CliniMACS device and resulted in a median number of 15.9×106 CD34 (2.5–41) stem cells, 147×106 CD56 NK-cells (9–552) and 413×106 CD14 monocytes (101–1100) per kg body weight. Median numbers of residual T and B cells were 56 000 (10 000–192 000) and 26 000 (2000–149 000) respectively. A reduced intensity regimen (melphalan (140mg/m2), thiotepa (10mg/kg), fludarabine (160mg/m2), OKT3 (0.1mg/kg)) was given in most patients. Co-transfused, HLA mismatched NK cells were traced in peripheral blood of 26 patients starting on day +1 with flow cytometry and appropriate HLA antibodies. Mean numbers of donor derived CD56+ cells/μl were: 3 (day 1), 22 (d 3), 17 (d 7), 75 (d 10), 197 (d 14). Theoretically, the mean absolute number of 4.8×106 co-transfused NK cells should have resulted in a mean number of 2000 cells/μl in peripheral blood of the patients. Comparison of this expected amount with the mean number of NK cells measured within the first week postransplant (25/μl, n=17 data points) showed, that only 1.2% of the cells remained in circulating blood. Thus, the majority of donor NKs did not circulate and probably homed to other compartments (bone marrow, lymph nodes). The number of NK cells cotransfused at day 0 partially influenced the speed of NK cell recovery: patients, who received > 100×106 donor NK cells/kg had significantly higher amounts of circulating cells at day 14 than patients, who received <100×106 donor NKs (240 vs. 140/μl, p<0.05). No significant difference was observed after d 14. Recovery of T cells was not influenced. Graft rejection occurred in 13%. This rate was similar to that of a historical control group (15% in patients who received CD34 positive selected grafts and standard conditioning regimens), although our study patients mainly received an intensity reduced regimen. We conclude, that co-transfused cells facilitated hematopoietic engraftment. Our approach resulted in low TRM (10% at d 365) and in a low relapse rate (20% at 2 years) in patients with microscopical remission (<5% blasts), but was insufficient in patients with active disease (80% relapse rate). We therefore investigated options to increase NK cell activity. Cytotoxicity against K562 cells and thymidine-uptake after PHA stimulation were measured prior and post depletion in 30 procedures. Median specific lysis at E:T ratio = 20:1 was 15% prior and 23% post depletion. Thus, NK activity was not hampered by the procedure. Specific lysis was significantly enhanced by pre-incubation with 1000 U/ml Interleukin (IL) 2 (44%, median) or 2ng/ml IL 12 (40%, median) or 1ng/ml IL 15 ( 53%, median) in vitro. In contrast, thymidine-uptake was reduced from 170 000 to 3000 counts due to profound T-cell-depletion. NK activity was weak against patient derived cryopreserved leukemic blasts without stimulation, but could be significantly increased by cytokine incubation in vitro. Therefore, a pilot study with infusions of IL 15 stimulated NK cells in vivo was started. Up to now, 6 patients received a total of 8 infusions with 12×106 - 150×106 ex vivo stimulated NK cells per kg bw without any side effects. Conclusions: co-transfusion of donor NK cells in haploidentical transplantation is feasible. Only a small portion of cells remained in circulating blood and homing to other organs is likely. NK activity could be increased by cytokines; the use of ex vivo IL 15 stimulated NK cells is currently evaluated. Clinical results suggest antileukemic and graft facilitating effects of donor NK cells.

scholarly journals Differentiation in vitro of T3+ large granular lymphocytes with characteristic cytotoxic activity from an isolated hematopoietic progenitor colony.

1988 ◽  
Vol 167 (3) ◽  
pp. 762-776 ◽  
Author(s):  
N Minato ◽  
M Hattori ◽  
T Sudo ◽  
S Kano ◽  
Y Miura ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Progenitor Cells ◽  
Hematopoietic Progenitor Cells ◽  
Nk Activity ◽  
Beta Chain ◽  
Large Granular Lymphocytes ◽  
Spleen Cells ◽  
Hematopoietic Progenitor ◽  
Granular Lymphocytes

Blast colonies were developed by rIL-3 from the spleen cells of mice pretreated with 5-fluorouracil (5-FU) in the methylcellulose cultures. When such IL-3-induced blast colonies were individually lifted up and recultured in the presence of rIL-3 and recombinant erythropoietin (rEpo), a variety of hematopoietic colonies developed from every single colony, including neutrophils, macrophages, eosinophils, megakaryocytes, mast cells, and erythroblasts. The results indicated that IL-3-induced blast colonies consisted of multipotential hematopoietic progenitor cells. By culturing individual IL-3-induced blast colonies in the presence of rIL-2 and irradiated peritoneal macrophages, on the other hand, the proliferation of homogeneous lymphoid cells was observed in 5 of 24 wells, each of which received a single blast colony. Morphologically, they were typical large granular lymphocytes (LGL), and thus it was indicated that LGL could be differentiated directly from the hematopoietic progenitor cells utterly in vitro by rIL-2 and accessory macrophages. From one of these culture wells, a continuous LGL line, IL3B1, was successfully obtained. The proliferation of IL3B1 was dependent on IL-2 in the presence of accessory macrophages, but they no longer responded to IL-3, nor to another T cell growth factor, IL-4. Flow cytometric analysis indicated that the phenotype of IL3B1 was Thy-1+,T3+,L3T4-,Lyt-2-,T200+ Asialo GM1+, whereas that of original IL-3-induced blast cells was Thy-1+,T3-,L3T4-,Lyt-2-,B220-. The results suggested that the expression of T3 molecules was induced in the process of LGL differentiation from the hematopoietic progenitor cells in vitro. Conforming to this, it was revealed that both gamma and beta chain genes of the TCR were rearranged in IL3B1. Northern blot analysis indicated that IL3B1 had abundant mRNA for gamma chain, while mRNA for beta chain was rather faint. Functionally, IL3B1 exhibited typical NK-patterned cytotoxic activity against a panel of tumor cell targets. In addition, they showed significant cytotoxic activity against normal bone marrow cells, as well as various factor-dependent myelogenous progenitor cell lines, all of which were resistant to endogenous NK activity of the fresh spleen cells. These results indicated that at least a set of T3+ LGL with rearranged TCR genes could be directly differentiated from isolated hematopoietic progenitor cells in vitro. Results also suggested that such a prethymically differentiated subset of T-lineage lymphocytes, namely T3+ double-negative LGL, had particular cytotoxic activity in addition to conventional NK activity, which might well contribute to feedback regulation of hematopoiesis.

Modulatory effect of metal lons on the immune response of fish: In vivo and in vitro influence of MnCl2 on NK activity of carp pronephros cells

1990 ◽  
Vol 20 (3) ◽  
pp. 241-245 ◽  
Author(s):  
Z. Ghanmi ◽  
M. Rouabhia ◽  
M. Alifuddin ◽  
D. Troutaud ◽  
P. Deschaux
Keyword(s):  
Immune Response ◽  
Nk 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.

scholarly journals Innate Immune Response of the Human Host to Exposure with Herpes Simplex Virus Type 1: In Vitro Control of the Virus Infection by Enhanced Natural Killer Activity via Interleukin-15 Induction

2000 ◽  
Vol 74 (16) ◽  
pp. 7196-7203 ◽  
Author(s):  
Ali Ahmad ◽  
Ehsan Sharif-Askari ◽  
Lama Fawaz ◽  
José Menezes
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Natural Killer ◽  
Herpes Simplex Virus Type ◽  
Nk Activity ◽  
Interleukin 15 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Infections with herpes simplex virus type 1 (HSV-1) in humans and in animal models are accompanied by enhanced natural killer (NK) activity. In vitro, HSV-1 also enhances the NK activity of human peripheral blood mononuclear cells (PBMC). The molecular basis of this enhanced NK activity, however, is not well characterized. We investigated the role of human interleukin-15 (IL-15) in this phenomenon and report here that HSV-1-mediated enhanced NK activity was abrogated by neutralizing antibodies for IL-15 but not for other cytokines (i.e., IL-2, IL-12, gamma interferon [IFN-γ], tumor necrosis factor alpha, or IFN-α). Anti-CD122 antibodies which block signaling through IL-2 receptor β chain, and therefore neutralize the effects of IL-15 (and IL-2), also abrogated this enhancement. Furthermore, HSV-1 increased the levels of IL-15 mRNA and the production of IL-15 in HSV-1-infected PBMC cultures. The neutralization of IL-15 in cocultures of PBMC with HSV-1-infected cells significantly increased HSV-1 production. These results strongly suggest a role for IL-15 in the HSV-1-mediated in vitro enhancement of NK activity and in the PBMC-mediated suppression of HSV-1 replication.

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