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Biomedical subjects

M Hokland

Publications and source records attributed to M Hokland.

At least 73 records · Page 4Linked to original sources
PubMed1986

Secretory products from thrombin-stimulated human platelets exert an inhibitory effect on NK-cytotoxic activity.

We have investigated the interaction between human platelets and the NK-system, with special emphasis on the action of secretory products from platelets in an NK assay with 51Cr-labelled K562 as target cells. Supernatants from thrombin-stimulated platelets added to the NK assay consistently decreased the NK-cytotoxicity by 40% +/- 4.3%, indicating the existence of secreted products from platelets as a source of NK-inhibiting substances. In contrast, no direct cytotoxic effect of these secretory products on the target cells (K562) was seen. Thus, normal human platelets, when stimulated with thrombin, are capable of secreting different, yet undefined factors, which significantly inhibit NK activity in vitro. The results also suggest that the role of products from contaminating in vitro activated platelets should be borne in mind when performing conventional NK assays.

Blood Platelets↗
PubMed1984

Effect of recombinant alpha interferon on NK and ADCC function in lung cancer patients: results from a phase II trial.

During a phase II trial of recombinant IFN-alpha given in doses of 50 X 10(6) units/m2 three times per week to lung cancer patients, 13 patients were evaluated longitudinally in NK and ADCC assays and in immunofluorescence tests enumerating the number of cells reactive with the new N901 NK-cell antibody. An increase in NK-cell activity could be demonstrated when values before and 24 h after the first injection of IFN were compared, but simultaneously the enhancing effect of IFN-alpha on NK-cells added to in vitro cultures was abolished, probably as a result of preactivation of NK cells in vivo. After 2-4 weeks of treatment, the majority of patients exhibited a pronounced decrease in NK-cell activity while still retaining the inability to be boosted by IFN added in vitro. Investigations with the NK antibody N901 showed that the initial increase in NK activity appeared concomitantly with an increase in the number of N901 positive cells, indicating that the mechanism behind this increase was an increase in the number of circulating NK cells. In contrast, the decrease in NK activity mentioned above was not followed by a similar decrease in the number of N901+ cells, and it was concluded that this decrease might be attributable to either an exhaustion phenomenon or to an induction of a refractory state of peripheral blood NK cells. When measuring ADCC activity, increases in lytic activity were seen only in patients in whom they could be attributed to non-IgG-dependent (NK-like) mechanisms. These data are discussed in relation to other clinical trials using leukocyte or recombinant IFN-alpha.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1983

Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA).

Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual fluorescence techniques disclosed that these cells were heterogenous with respect to the expression of a series of differentiation and activation antigens defined by monoclonal antibodies. Thus, whereas all CALLA+ cells were Ia+ and expressed two activation antigens, J2 and T10, only 30-50% expressed B1 antigen. Furthermore, using methanol-fixed cells, it could be shown that approximately 20% contained intracytoplasmic mu chains (cyto-mu) and that approximately 15% were positive for the terminal transferase enzyme (TdT) marker. The CALLA+ fetal cells thus closely resemble the childhood acute lymphoblastic leukemia cell with respect to surface marker phenotype. A population of CALLA- cells devoid of mature erythroid and myeloid surface markers was found to contain higher numbers of TdT+ cells but lower numbers of cyto-mu, B1, and Ia+ cells than the CALLA+ subset. In vitro analysis of normal, purified CALLA+ cells demonstrated that incubation at 37 degrees C with J5 monoclonal antibody specific for CALLA resulted in the specific modulation of surface antigen. Similar results have previously been obtained with CALLA+ tumor cells. Although phenotypic analysis of CALLA+ cells suggests that these cells are relatively immature lymphoid cells, CALLA+ cells do not appear to contain either myeloid precursor cells (CFU-G/M) or the earliest lymphoid stem cells.

Antibodies, Monoclonal↗
PubMed1983

Interferon-induced changes in expression of antigens defined by monoclonal antibodies on malignant and nonmalignant mononuclear hematopoietic cells.

The effect of alpha interferon (alpha IFN) on the expression of histocompatibility--as well as differentiation antigens on normal and malignant hematopoietic mononuclear cells--were investigated by cell cytofluorometry using a panel of monoclonal antibodies (MoAbs). An increase in the expression of HLA-antigens detected by beta 2-Microglobulin (beta 2-M) could be demonstrated for peripheral blood mononuclear cells, non-T cells, Null cells, activated T cells, fetal thymocytes, adherent cells, and on four malignant non-T lymphoblastoid cell lines. In contrast, no significant differences were observed in the expression of antigens specific for B-lymphocytes (B1), T-lymphocytes (T3, T4, T6, T8, T11), NK-cells (901) and adherent cells (Mo1-4). Likewise, the expression of Ia-antigens remained unaltered on non-T cells, Null cells, and monocytes. The only other effect of IFN was an increase in the number as well as the amount of lymphocytes expressing the T10 antigen. It thus seems that the enhancing effect of IFN on resting cells of the immune system is highly selective. On the four lymphoblastoid cell lines, the expression of the common acute lymphoblastic leukemia antigen (CALLA) was significantly decreased concomitantly with the increase in MHC-antigens. On the other hand, the density of both a HLA-D related Ia antigen (I2) and a B-lymphocyte differentiation antigen (B1) remained unaltered following IFN treatment. The implications of these findings are discussed.

Antibodies, Monoclonal↗
PubMed1983

13 native human interferon-alpha species assessed for immunoregulatory properties.

Human leukocytes treated with Sendai virus yield interferon predominantly of the alpha-type (HuIFN-alpha). Successful attempts to purify these "native" species have been performed and the final analysis, which included an SDS-PAGE disclosed 13 stained and separated IFN-proteins in the molecular weight-range of 16.6-23.5 kD. These stained IFN proteins were eluted individually from the gel slices and assessed for antiviral activity in human, monkey, and bovine cells, as well as for immunomodulatory effects (in vitro) on human lymphocytes. Based on equal amounts of (human) IFN units, as determined by IFN titration on human cells, the "immunological efficacies" of the 13 different HuIFN-alpha species were determined in three different immunological systems with the following results: (1) Augmentation of the NK function was a property of all species, although the two lower species (16.6 kD, 16.9 kD) were clearly less efficient with "titers" in the NK system reduced 25-fold. (2) Enhanced expression of HLA on lymphocyte membranes was induced by all the HuIFN-alpha species to the same extent. (3) Addition of IFN to mixed lymphocyte reaction (MLR) augmented the CML outcome of the cultures. In this system all 13 species exerted their effect equally well; no clear inferiority or superiority of individual species were seen. It is concluded that the fractionation of the IFN-alpha into 13 species does not give rise to IFN species which are specific only for some functions and not for others. All species exert all functions, although the relatively "immunological" titers in the NK system varied within the species.

Antiviral Agents↗
PubMed1983

Selective effects of alpha interferon on human T-lymphocyte subsets during mixed lymphocyte cultures.

Mixed lymphocyte reaction (MLR) cultures of human lymphocyte subsets with or without the addition of physiological doses of human alpha interferon (IFN-alpha) were compared with respect to surface marker phenotypes and proliferative capacities of the responder cells. A selective depression on the T4 (inducer) T-cell subset could be demonstrated as a sequence of events: decreased fluorescence intensity of the T4 inducer cells (day 2 of culture), decreased percentages of T4 cells as demonstrated by cell cytofluorometry (days 3-6 of culture), and decreased 3H-thymidine incorporation of purified T4 cells and decreased numbers of T4 cells harvested from IFN MLRs (days 5-6 of culture). In contrast, it was shown that the T8 (cytotoxic/suppressor) subset in MLRs was either not affected or slightly stimulated by the addition of IFN. The depression of the T4 cells by IFN was accompanied by a decrease in the number of activated T cells expressing Ia antigens. On the other hand, IFN MLRs contained greater numbers of cells expressing the T10 differentiation antigen. In experiments with purified T-cell subsets the IFN effect was exerted directly on the T4 cells and not mediated by either T8 suppressor cells or monocytes. These findings are discussed in relation to other immunoregulatory effects of IFN-alpha.

Antigens, Surface↗
PubMed1982

The relationship between human T-lymphocyte subsets defined by monoclonal antibodies and by avidity differences to sheep erythrocytes.

By E-rosette sedimentation procedures and fluorescence activated cell sorting of monoclonal antibody-coated T lymphocytes, we have investigated the relationship between the human T lymphocyte subsets defined by the monoclonal antibodies against the T4 and T8 antigens and those defined by avidity differences to sheep erythrocytes. Through a correlation was demonstrated between the T4+ (inducer) cells and the high avidity ("active") T cells and between the T8+ (suppressor) cells and low avidity T cells, these subsets were far from identical, and it is concluded that the application of monoclonal antibodies represents another valuable and standardized approach for estimating T cell subsets.

Animals↗
PubMed1981

Increased expression of beta 2-microglobulin and histocompatibility antigens on human lymphoid cells induced by interferon.

Normal human peripheral blood lymphocytes were incubated in the presence of different concentrations of interferon for various incubation periods. Subsequently, the amount of beta 2-Microglobulin and HLA-A, B and C surface antigens was estimated by means of quantitative immunofluorescence (flow cytofluorometry) and by a radioimmunoassay for beta 2-Microglobulin. It was found that the amounts of these MHC antigens increased in a dose and time-dependent way after interferon treatment. Furthermore, the influence of different temperatures on this IFN-induced increase in beta 2-Microglobulin was gradually enhanced after incubation at 37 degrees C to 39 degrees C incubation mostly suppressed the beta 2-Microglobulin increase observed at 39 degrees C. The total amount of membrane associated beta 2-Microglobulin was estimated by a radioimmunoassay. After interferon treatment a beta 2-Microglobulin increase was observed ranging from 39% to 122% in different experiments. It is shown that interferon is the substance responsible for the effects on lymphocytes reported here, because completely pure interferon-proteins had the same activity as has been shown for partially purified interferon preparations.

Beta-Globulins↗
PubMed1981

Corticosteroids decrease the expression of beta 2-microglobulin and histocompatibility antigens on human peripheral blood lymphocytes in vitro.

The in vitro effect of two different glucocorticoids (prednisolone and dexamethasone) on the expression of beta 2-microglobulin and HLA-A-A, -B and -C-antigens on the surface of cultured lymphocytes was measured by quantitative immunofluorescence (flow cytofluorometry) and by a radioimmunoassay. Both antigens were found to be decreased, dexamethasone typically in a concentration of 10-6 mol/l causing a decrease in surface beta 2-microglobulin of 15% after an incubation period of 24 hr. The expression of two other lymphocyte surface antigens, Igm and Thy antigens, measured in parallel with beta 2-microglobulin and HLA antigens, was not affected by the same culture conditions. The steroid effect was not due to masking of the affected antigens, but was completely abolished by inhibition of protein synthesis.

Adult↗
PubMed1981

Malignant monoblasts can function as effector cells in natural killer cell and antibody-dependent cellular cytotoxicity assays.

This is the first report describing natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) of malignant monoblasts. Pure acute monoblastic leukemia was diagnosed in bone marrow aspirations from two patients by use of conventional cytochemical methods as well as multiple immunologic techniques including detection of ALL antigens and terminal transferase. The malignant cells were subsequently found to be potent effectors in NK and ADCC assays. Addition of partially purified alpha-interferon to the in vitro cultures was found to have an enhancing effect on NK activity, whereas no modulation was seen in ADCC. These findings are discussed in the light of our present knowledge of lymphoid NK cells.

Aged↗
PubMed1980

Effects of polycationic compounds on mitogen stimulation.

The effects of polycations added to phytomitogen stimulated human lymphocyte cultures have been studied. Within certain dose ranges all polycations tested gave rise to augmented thymidine uptake in mitogen stimulated cultures. The optimum enhancing concentrations of polycations was depending on the serum concentration in the culture medium. This was found to be due to two types of interactions: (a) Interference with mitogen binding serum factors, (b) Reaction with immunosuppressive serum proteins. Suggestive evidence for an affect of polycations also directly on the cells was found by pretreatment and cell density experiments. The direct effect on cells was found not to be due to monocyte bypass or to activation of non-T cells by the mitogen. It is pointed out that effect of chemicals on in vitro immunresponses have to be considered in relation to the charge properties of the compound.

Cell Survival↗