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At least 19 recordsLinked to original sources
PubMed1983

Murine natural antitumor antibodies. III. Interferon treatment of a natural killer-resistant lymphoma: augmentation of natural antibody reactivity and susceptibility to in vivo natural resistance.

Treatment of a natural killer cell-resistant (NKR) DBA/2 lymphoma with L-cell interferon (IFN) enhanced its reactivity to serum natural antibody in vitro in cytolysis and absorption studies and increased the in vivo acquisition of natural and antitumor antibody in the peritoneal cavity. The IFN effects were both time- and dose-dependent. In vitro IFN-treated, [131I]5-iodo-2'-deoxyuridine-labeled tumor cells, when injected ip into normal syngeneic mice, were more rapidly eliminated than were untreated control cells. IFN treatment of the NKR tumor decreased "cold-target" inhibition of NK lysis and did not alter binding or lysis by macrophages. These findings indicated that the enhancement of natural resistance to the IFN-treated tumor did not involve NK cells or macrophages and suggested that IFN may enhance host antitumor resistance by increasing tumor reactivity to antibody.

Animals↗
PubMed1990

Natural killer cell immunodeficiency in siblings: defective killing in the absence of natural killer cytotoxic factor activity in natural killer and lymphokine-activated killer cytotoxicities.

A immunodeficiency of natural killer cells as effectors for natural killer and lymphokine-activated killer cytotoxicities was first demonstrated in siblings. Two of three male siblings persistently lacked natural killer activity against K562 target cells as assayed by a 51Cr-release assay: percent lysis values were less than 1.0% as compared to the normal lymphocyte values of 43.5% +/- 6.2% (mean +/- SD). Their lymphocytes did not develop natural killer cell activity by changing effector to target ratios, prolonging the incubation time, or stimulating them with interferon-alpha or interleukin 2. Numbers of lymphocytes bearing Leu-7, CD16, or NKH-1 were normal but those of Leu-7-, CD16+ cells were decreased as estimated by flow cytometry. Single cell-in-agarose assays showed normal numbers of natural killer cells capable of binding to a target cell but incapable of killing it. They had depressed levels of lymphokine-activated killer activity, which was totally eliminated by the treatment with OKT3 and complement. This result indicates that the patients' natural killer cells are also defective in the capacity to work as effectors for lymphokine-activated killer activity. The patients' natural killer cells did not produce natural killer cytotoxic factor activity. Antibody-dependent cellular cytotoxicity and cytotoxic T lymphocyte cytotoxicity were normal. These results demonstrate a selective natural killer cell deficiency as effectors for natural killer and lymphokine-activated killer cytotoxicities with a familial tendency, in which there is defective killing with the absence of natural killer cytotoxic factor activity.

Child↗
PubMed1991

Natural killer cell immunodeficiency in patients with chronic myelogenous leukemia. IV. Interleukin-1 deficiency, gamma-interferon deficiency and the restorative effects of short-term culture in the presence of interleukin-2 on natural killer cytotoxicity, natural killer-target binding and production of natural killer cytotoxic factor.

We report herein that defective natural killer (NK) cell cytotoxicity, NK cytotoxic factor (NKCF) production and NK target binding ability of patients with chronic myelogenous leukemia (CML) are functionally restorable after short-term culture (less than 1 week) with recombinant interleukin-2 (rIL-2). We have previously reported that, despite normal to increased numbers of CD16+ large granular lymphocytes, fluorescence-activated-cell-sorted NK cells from CML patients are profoundly defective in NK cell activity and are unable to lyse the CML blast-crisis-derived, NK-sensitive target K562. Since we and others have also previously shown that the defective NK cytotoxicity from CML patients is restorable after 1-4 weeks of incubation with rIL-2, we therefore deemed it important to study the kinetics of IL-2-mediated NK restoration at earlier time intervals (less than 1 week). In the present report, we have demonstrated a significant restoration of NK cell cytotoxicity in CML patients against K562 after 5 days of short-term culture with rIL-2. In addition, recovery of NKCF production and restoration of target-binding capacity to normal levels by NK cells from CML patients were also observed after short-term (less than 1 week) rIL-2 treatment. Finally, we have demonstrated in the present report that adherent cells and peripheral-blood lymphoid cells from CML patients, as compared to normal controls, are unable to produce IL-1 beta and interferon-gamma, respectively, after stimulation with phorbol myristate acetate (IL-1 beta) and phytohemagglutinin-M (interferon-gamma).

Antigens, CD↗
PubMed1986

Natural cytolytic activity in mice with natural or induced cellular defects. I. Differential ability of in vitro interleukin-2 addition to augment natural cytolytic function.

The ability of in vitro addition of recombinant interleukin 2 (rIL-2) to differentially enhance natural cytotoxicity was assessed using cells from mice with natural and induced cellular defects. In vivo treatment with most immunosuppressive or cytoreductive agents, anti-asialo-GM1 antibody, or gamma irradiation dramatically reduced in vitro cytotoxicity against natural killer (NK) sensitive targets by direct reduction in either percentage specific lysis or lytic units per spleen. In most cases, in vitro addition of rIL-2 (at concentrations causing augmented NK function in cells from naive Balb/C mice) enhanced cytotoxic activity of cells from treatment groups to a normal value but not within the rIL-2-enhanced range of nontreated animals. Additionally, cytotoxic activity of cells from animals treated with certain drugs or gamma irradiation could be augmented by rIL-2 when measured by percentage lysis but not lytic units per spleen. In vivo treatment with cyclosporin A did not affect natural cytotoxic activity and addition of rIL-2 augmented the NK activity in a similar fashion to the profile of naive cells. In experiments using cells from beige (C57Bl/6-bg) mice which have a natural defect in NK activity against YAC-1 targets, addition of rIL-2 (at concentrations causing augmented natural cytotoxic function in cells from C57Bl/6 mice) could not effectively enhance in vitro natural cytotoxic function.

Adjuvants, Immunologic↗
PubMed1986

Natural cytotoxic T cells (NCTC) that differ from natural killer (NK) and natural cytotoxic (NC) cells are present in Peyer's patches of mice.

We have examined noninduced cytotoxicity of mouse gut associated and peripheral lymphoid tissues for a wide variety of syngeneic as well as allogeneic cell lines and lymphoblasts. Lymphoid cells from Peyer's patches were found to lyse these targets in a 3-hr chromium release assay whereas lymphoid cells from intestinal mucosa, mesenteric or peripheral lymph nodes, spleen, and thymus did not. The variety of targets toward which Peyer's patch cells were cytotoxic established the latter as nonspecific and H-2 unrestricted. The cell responsible for the lytic event was identified as possessing Thy 1.2 and Ia surface antigens. This naturally cytotoxic T cell (NCTC) was found to be adherent to nylon-wool but not to plastic plates. Although both natural killer cell (NK) and non-NK targets served as targets for the NCTC, the latter were further differentiable from NK cells by lack of asialo GM1 surface marker, which is present on NK cells. In addition, NCTC remained fully functional in mice given either of the drugs cyclophosphamide or cortisone. Each of these drugs, in the doses used, markedly reduced poly(I:C)-induced NK activity. Thus, NCTC differs from NK on the basis of the spectrum of targets against which it is functional, phenotypic surface markers, insusceptibility to stimulation with poly(I:C), and insensitivity to diminution by the immunosuppressive drugs cyclophosphamide and hydrocortisone. Since NCTC is a Thy 1.2 antigen-bearing cell and is detectable in a 3-hr cytotoxic assay, it also differs from the natural cytotoxic (NC) cell. NC lacks the Thy 1.2 marker and becomes detectable only in an 18-hr cytotoxic assay. Thus, NCTC is neither an NK nor an NC cell. We have discussed the possibility that the three naturally occurring cells may be related by being dedifferentiated descendants of an antigen-specific cytotoxic T lymphocyte (CTL). Alternatively, since NCTC is confined to an anatomical site prone to ample antigenic exposure and is still identifiable as a T cell, it may be in linear transition from the CTL to the NK or NC stages.

Animals↗
PubMed1983

Recognition specificities, development, and possible biological function of natural killer cells in the mouse. I. Spleen focus forming assay for natural killer activity and analysis of lectin-like recognition structures on the surface of murine natural killer cells.

A number of simple sugars have been tested and found to be effective in blocking lysis of YAC-1 tumor target cells by nonimmune murine natural killer (NK) effector cells. Using a spleen fragment culture system an assay has been developed which allows us to compare the inhibition of lysis observed in replicate culture wells prepared from cells contained in one spleen fragment (less than or equal to 1 X 10(6) cells). The inhibition pattern of any well was found to fall naturally into 1 of 25 (of the total 128 possible tested) patterns. Using this panel analysis of NK activity in individual mice of the same or different strain has been compared. Our data suggest that within any given strain the inhibition pattern of NK effector cells is quite uniform. Consistent differences are seen between strains which are interpreted in terms of a genetic control of the final expression of the NK recognition repertoire. In adult F1 hybrid individuals the pattern of recognition by NK cells is best considered a result of the codominant expression of genes contributed by each parent.

Animals↗
PubMed1986

Natural killer cells in murine muscular dystrophy. IV. Characterization of Percoll fractionated splenic and thymic natural killer cells and natural killer-sensitive thymocyte targets.

The Natural Killer (NK) activity in the thymus and NK-sensitive thymocyte targets of dystrophic mice was investigated. Dystrophic and normal mouse thymocytes or spleen cells were layered on discontinuous Percoll gradients (5 or 10% increments, respectively) between 40 and 70% and centrifuged at 1700 g for 30 min. All fractions were tested for either NK activity or used a 51Cr-labeled NK-sensitive targets in a 6-hr 51Cr release assay. The density interface between the 50% (1.060 g/ml) and 60% (1.075 g/ml) Percoll fractions of either dystrophic or normal mouse spleen cells and the 40% (1.050 g/ml) and 50% (1.060 g/ml) Percoll fractions of either dystrophic or normal mouse thymocytes were found to contain the largest proportion of NK activity using YAC-1 lymphoma tumor cells as targets. In addition, the NK activity in dystrophic mouse spleen cells and thymocytes was significantly greater when compared with normal mouse controls. Target binding cell studies revealed that these Percoll fractions of dystrophic mouse spleen cells and thymocytes had greater numbers of conjugate-forming cells when compared with normal control groups. Cell depletion experiments using either anti-Thy 1.2, anti-asialo-GM 1 or anti-NK-1 plus complement treatment revealed that the cell responsible for NK activity in the 50% Percoll fraction interface of dystrophic mouse spleen cells was asialo-GM 1 positive. NK-1 positive, and partially Thy 1.2 positive. However, the cells displaying NK-activity in the thymus of normal or dystrophic mice were found to be highly Thy-1.2 positive and peanut agglutinin (PNA) negative. The density interface between the 60% (1.075 g/ml) and 65% (1.081 g/ml) Percoll fractions of either normal or dystrophic mouse thymocytes contained the largest proportion of NK-sensitive target cells. Interestingly, the 60% Percoll fraction of dystrophic mouse thymocyte targets was significantly more susceptible to NK-mediated lysis than that of the normal mouse thymocyte population. Cell depletion experiments revealed that the NK-sensitive thymocyte population was similar in both mice, that is, Thy-1.2 positive, cortisone sensitive, PNA positive, Dolichos biflorus (DBA) negative and asialo GM-1 negative. The results indicate that there are density differences between splenic and thymic NK cells. In addition, there are density and phenotypic differences between thymic NK cells and thymic NK-sensitive target cells. The findings support the hypothesis that there are different populations of NK cells.

Animals↗
PubMed1984

Life history of cells mediating natural resistance to tumor cells and bone-marrow transplants: the respective roles of cell lineage commitment and host environment in determining strain characteristics of natural resistance to foreign marrow grafts.

A class of cells present in the blood and lymphoid tissues of mammals produces rapid cytolysis of tumor cells on first contact. Abundant evidence suggests that such natural killer (NK) cells play a role in tumor immunosurveillance in vivo. A similarly prompt and spontaneous activity can cause the rejection of foreign marrow transplants. These phenomena are known collectively as natural resistance. The cells mediating natural resistance are lymphoid in morphology, but are neither T nor B lymphocytes. Kinetically, NK cells and cells mediating natural resistance to foreign marrow grafts are themselves nondividing but are rapidly renewed from radiosensitive proliferating precursors in the bone marrow. They appear to have no long-lived (memory) component. Newly formed NK cells have a short residence time in the spleen. Other general properties of the natural-resistance cell lineage, including strain variation, ontogeny, and cell phenotype, are reviewed in this article. The present study aimed to examine the respective roles of cell lineage commitment and of the host environment in determining strain characteristics of natural resistance to foreign marrow grafts. Chimeras produced by inoculating mice of a strain that normally has little or no natural resistance with bone marrow from adult mice of a highly resistant strain develop resistance to a third-party marrow allograft. Such chimeras do not develop the full rejection capacity of the high-resistance strain, however; and chimeras created by inoculating marrow from infant mice develop less resistance than those reconstituted by bone marrow from adult mice. The results demonstrate that the ability to reject foreign marrow grafts develops as an intrinsic property of the natural-resistance cell lineage. The host environment may provide an additional influence, however, particularly in the initial development of natural resistance in early postnatal life.

Animals↗
PubMed1986

Augmentation of natural killer cytotoxicity by alpha or gamma natural and recombinant interferons and interferon inducers. Effect of monocytes.

We investigated the effect of human peripheral blood monocytes on the augmentation of natural killer cytotoxicity by alpha or gamma natural and recombinant interferons (IFN) and certain interferon inducers. We observed that: (1) in the majority of the donors examined (75%) human peripheral blood monocytes do not affect natural killer cytotoxicity, determined by a 4-hour chromium-51 release assay, against target cells from hemopoietic human tumor cell lines. (2) Monocytes are not required and do not affect the augmentation of natural killer cytotoxicity by Escherichia coli-derived IFN-gamma, natural human IFN-gamma, E. Coli-derived IFN-alpha 2 or natural human IFN-alpha. E. Coli-derived IFN-gamma and natural human IFN-gamma have been reported to activate monocyte cytotoxicity determined in 72-hour assay. (3) Monocytes are not required for the augmentation of natural killer cytotoxicity against target cells from hemopoietic tumor cell lines by polyinosinic acid-polycytidylic acid or staphylococcal enterotoxin A.

Cells, Cultured↗
PubMed1985

Anticancer activity of a natural product, viva-natural, extracted from Undaria pinnantifida on intraperitoneally implanted Lewis lung carcinoma.

A natural product, named Viva-Natural, extracted from a dietary seaweed Undaria pinnantifida has been found to be therapeutically active against Lewis lung carcinoma (LLC). Viva-Natural also demonstrated moderate prophylactic activity against LLC in allogeneic mice. The active principle(s) which was concentrated in the water-insoluble fraction of Viva-Natural was essentially noncytotoxic in KB cell cultures, and probably a polysaccharide. Viva-Natural was found to be significantly effective in enhancing the natural cytolytic activity of peritoneal macrophages against KB cells as targets in in vitro assay, suggesting that the antitumor action of Viva-Natural might be indirect through the activation of nonspecific immune systems. A combination therapy of Viva-Natural and standard anticancer drugs was additively or synergistically effective.

Animals↗
PubMed1992

[Chemical investigation of naturally occurring drug materials. Elucidation of scientific basis for traditional medicines and exploitation of new naturally occurring drugs].

In search of new biologically active compounds in nature, we have been investigating naturally occurring substances on the following subjects: I. chemical studies on naturally occurring drug materials [a) elucidation of bioactive constituents in natural drugs, b) elucidation of scientific basis for crude drug processing, and c) investigation of bioactive constituents in food materials], II. exploitation of new pharmaceuticals in nature [a) investigation of marine natural products and b) exploitation of Indonesian medicinal plants], and III. synthetic studies on bioactive natural products [a) chemical modification of naturally abundant carbohydrates and terpenoids and b) synthetic studies of complex lipids]. This article reviews the results obtained in our laboratory since 1978 on the subjects of I-a, b, c, II-a, and III-a.

Alkaloids↗
PubMed1987

In vitro synergistic effects of natural human tumor necrosis factor and natural human interferon-alpha.

Tumor necrosis factor and interferons are multifunctional cytokines. The present studies were undertaken to investigate the biologic interactions of highly purified natural human tumor necrosis factor and highly purified natural human interferon-alpha, which were derived from a B cell acute lymphatic leukemia line (BALL-1 cells) sensitized with hemagglutinating virus of Japan (HVJ). Combined treatment with natural human tumor necrosis factor and natural human interferon-alpha synergistically inhibited the in vitro proliferation of P4788 cells derived from a human colon cancer. Flow cytometric analysis of the cell cycle of asynchronous cells indicated that target cells treated with natural human tumor necrosis factor alone accumulate in the S phase. This accumulation in the S phase of the cell cycle was augmented by combined treatment with natural human tumor necrosis factor and natural human interferon-alpha. The growth inhibitions appeared to be a result of arrest in the S phase of the cell cycle. Combined treatment with these cytokines had potent cytostatic and cytotoxic effects on most of the tested malignant cell lines of human epithelial origin.

Cell Cycle↗
PubMed1988

Altered natural killer cell activity in childhood acute non-lymphoid leukaemia. Augmented natural killer cell activity and cells expressing the Leu 7 and Leu 11b (CD 16) markers in the bone marrow of children in remission.

Peripheral blood and bone marrow mononuclear cells from 25 children with acute non-lymphoid leukaemia were analysed for natural killer cell activity and for cells with the Leu-7 and Leu-11b (CD 16) markers. Significantly reduced spontaneous cytotoxicity was detected in peripheral blood from children with untreated and active acute non-lymphoid leukaemia compared with that of the controls (P = 0.01 and P less than 0.05). Patients in remission, however, had normal natural cytotoxicity and normal numbers of Leu-7 and Leu-11b (CD 16)-positive cells. The natural killer cell activity in bone marrow from patients with untreated acute non-lymphoid leukaemia was also significantly reduced (P = 0.025). On the other hand, patients in remission had both an increased percentage of Leu-7 and Leu-11b (CD 16)-positive cells (P less than 0.05) and an increased natural killer cell activity (P less than 0.0005) in their bone marrow cells in comparison with the control group. This augmented natural killer cell activity is most probably a result of anti-leukaemic treatment. Stimulation with recombinant alpha interferon and recombinant interleukin 2 caused an increase in natural killer cell activity that was both significant and normal in both peripheral blood and bone marrow from children with acute non-lymphoid leukaemia.

Acute Disease↗
PubMed1985

Natural and radiation-induced cataracts in man and mouse, and natural macular degeneration in man: proposed mechanisms.

A unified theory of growth and age-dependent disorders is applied to the interpretation of epidemiological data for natural and radiation-induced cataracts and natural macular degeneration in man. Using the same unified theory, mechanisms are also proposed to explain the experimental evidence for natural and radiation-induced lenticular opacities in the lens of the mouse. Epidemiological and experimental data are strikingly consistent with the hypothesis that natural cataract formation is an autoaggressive process but the details of pathogenesis differ greatly between the two species. Radiation dose-response relations reflect these contrasts. Lenticular opacities in the nuclear-bomb survivors at Hiroshima and Nagasaki were probably induced by a 'single-track' mechanism. Radiation-induced generalised opacification in the lens of the mouse results from a 'multi-track' process. The pathogenesis of natural macular degeneration in man happens to have close parallels with that of natural opacification in the mouse. We discuss some implications of these inferences for the phenomenon of radiation-induced lethal disorders in man.

Age Factors↗
PubMed1980

Quantitative studies of natural immunity to solid tumours in rats. Persistence of natural immunity throughout reproductive life, and absence of suppressor cells in infant rats.

Consideration of cell-mediated cytotoxicity as an enzyme-substrate reaction provided a theoretical and practical basis for the quantification of natural immunity to solid tumours. The natural cytotoxic activity of spleen cells from normal rats towards cultured target cells from solid tumours, measured in a 6 h chromium release assay, developed between 2 and 5 weeks after birth and, in contrast to previous reports of natural cytotoxicity against lymphoid tumour cells, showed no sign of decline up till at least 22 months of age. Both virgin and breeder (multiparous) females showed equally good maintenance of natural immunity, and the apparent specificity of this natural immunity on a panel of four target cells did not change between 8 weeks and 18 months of age. The low level of natural immunity in infant spleen, and also in adult lymph nodes and thymus, was not caused by suppressor cells but rather by an absence of appropriate effector cells.

Aging↗