Search PubMed⌕ Search

Biomedical subjects

P Perlmann

Publications and source records attributed to P Perlmann.

At least 217 records · Page 12Linked to original sources

Determination of the immunoglobulin class of complement-dependent cytotoxic antibodies in serum of D23 hepatoma-bearing rats.

The immunoglobulin class of the complement-dependent cytotoxic antibodies in serum from D23 hepatoma-bearing rats (D23 TBS) for D23 hepatoma cells was analysed. When studied by affinity chromatography with concanavalin A, protamine, or staphylococcal protein A conjugated to Sepharose, the cytotoxic activity bound to the former two but not protein A. The binding fractions were further characterized by column chromatography on Sepharose CL-4B. The cytotoxic activity was recovered exclusively in the high molecular weight fractions corresponding to human IgM. Monitoring with IgG- or IgM-specific rabbit antibodies indicated that these high molecular weight cytotoxic fractions contained both IgG and IgM. However, fractionation of D23 TBS at low pH suggested that cytotoxicity was due to IgM antibodies rather than to immune-complexed IgG antibodies. This was supported by the findings that rabbit antirat IgM antibodies inhibited the cytotoxicity of TBS completely when added at high dilutions.

Animals↗

Effect of Fc-receptor modulation on mumps-virus-dependent lymphocyte-mediated cytotoxicity in vitro.

The natural cytotoxicity of peripheral blood lymphocytes (PBL) from normal human donors to a variety of tissue culture target cells increases upon brief exposure of lymphocytes to mumps virus. The effector cells operative in this system have Fc receptors for IgG (FcR), since cytotoxicity was abolished when FcR+ cells were removed by passage of the lymphocyte over immune-complex columns. When PBL were treated with immune complexes for 16 h at 37 degrees C, their FcR activity was sharply decreased (modulation), as indicated by a significantly reduced capacity of the treated cells to display antibody-dependent cytotoxicity (ADCC). Modulation had variable effects on natural cytotoxicity. In contrast, the virus-dependent cytotoxicity above the natural cytotoxicity remained essentially unchanged, indicating that a functionally intact FcR is not required in this system for carrying out cytolysis.

Antibody-Dependent Cell Cytotoxicity↗

Inverse correlation between cell-surface adhesiveness and malignancy in mouse fibroblastoid cell lines.

The correlation between tumorigenicity and cell-surface adhesiveness was investigated in eight mouse fibroblastoid cell lines. Four of the lines (Mc 11-Mc 15) were derived from mouse MC-induced fibrosarcomas, two were derivatives of L cells (A9, A9HT), and two (clone 3 and clone 7 H7F4) were obtained by fusion of A9HT cells with normal diploid mouse lymphocytes. Quantitative comparison of cellular adhesive properties by the Latex particle adherence assay indicated that higher malignancy of some lines (Mc 11, 13, 14, A9HT cl 7 H7F4) was regularly associated with lower cell-surface adhesiveness and conversely, lower malignancy of the other lines (Mc 15, A9, cl 3) with high cell-surface adhesiveness. The differences in adhesiveness of cell lines of high and low malignancy were determined by cell subsets not attaching and Latex particles (24.6-61.9% of cells in highly and 4.6-12.0% in slightly tumorigenic lines) and cell subsets attaching more than 25 Latex particles per cell (14.6-17.2% in highly and 46.1-71.4% in less tumorigenic lines).

Animals↗

A rosette assay for the determination of C 1 q receptor-bearing cells.

A rosette assay for the identification of cells with receptors for C 1 q is described. Glutaraldehyde-treated bovine erythrocytes bound C 1 q specifically, and the reagent thus prepared provided a valid indicator for rosette formation mediated by C 1 q receptors. The presence of these receptors on the membrane of a subset of human peripheral lymphocytes (mainly non-G cells) and on B-derived lymphoblastoid cells was confirmed. Rosette formation was dependent on the number of C 1 q molecules bound per indicator cell and was specifically inhibited by soluble native C 1 q and pepsin-resistant C 1 q fragments. These data, together with the reduced binding activity of C 1 r-C 1 s-associated C 1 q, indicated that the C 1 q binding sites for lymphoid membranes are expressed on the collagen-like moiety, C 1 q rosette formation provided a simple new procedure for fractionation of human lymphocyte populations and separation from phagocytes that do not express receptors for C 1 q.

Animals↗

Transferrin can replace serum for in vitro growth of mitogen-stimulated T lymphocytes.

Activation of human T cells by mitogens was compared in cultures containing serum, human serum albumin or purified human transferrin as growth support. The mitogenic effect of the lectins leucoagglutinin, concanavalin A and Wistaria floribunda agglutinin was measured as incorporation of [3H]thymidine into the cellular DNA of the lymphocytes. Three different preparations of transferrin were all able to fully substitute serum or serum albumin as growth promotors, when present at concentrations of 10 microgram/ml or more. A small contamination of transferrin in the human serum albumin preparations used was shown to be responsible for their growth-supporting effect, while no need for the presence of albumin itself could be demonstrated.

Cells, Cultured↗

Human T-lymphocyte subpopulations: alterations in systemic lupus erythematosus.

Sharply reduced proportions of T cells with Fc receptors for IgG (TG cells) were observed in blood samples from patients with systemic lupus erythematosus (SLE), mainly with active disease. This T-cell subset has previously been shown to be a suppressor in the pokeweed mitogen (PWM)-dependent B-cell differentiation. In contrast, the percentages of T cells with Fc receptors for IgM (TM cells), which have been shown to help immunoglobulin production, were not different from those of normals. TG cells present in the circulation of SLE patients were analysed for their functional capacities in antibody-dependent cell-mediated cytotoxicity and in the suppression of a PWM-induced B-cell differentiation. In both these assays TG cells from SLE patients had normal effector cell activity. This suggests that thr than a qualitative type.

Adolescent↗

Antibody dependent cellular cytotoxicity and mitogen responsiveness of human peripheral blood lymphocytes differing in avidity for sheep erythrocytes.

To characterize the effector cells (K-cells) in antibody-dependent cellular cytotoxicity (ADCC) against a nucleated target cell (El 4), human peripheral blood lymphocytes (PBL) were fractionated by rosette sedimentation into subpopulations differing in avidity for sheep erythrocytes (E). The fractions obtained were assayed for surface markers, and as a functional T cell marker, for responsiveness to the mitogen leucoagglutinin (La). By depleting PBL of E-receptor-bearing cells (Et+), approximately half of the cytotoxic potential was found in the Et-depleted fraction. While the Et+ fraction had low activity on a per cell basis, it nevertheless contained a significant proportion of the original cytotoxicity. By sequential E-rosetting, fractions binding E with high avidity (Et+), low avidity (Et+) or not at all (E-) were obtained. Both E-binding fractions consisted primarily of T-cells, as judged from their surface marker profiles. Both fractions responded well to La, but with different dose optima. The E- fraction contained primarily B-and null cells and did not respond to La. Significant K-cell activity was found in all these fractions. The results show that a significant fraction of the K-cells have receptors for E and these can be of either high or low avidity. Since both EH+ and EL+ fractions respond well to La and contain K-cells, a T-cell origin of the latter is suggested. However, whether or not cytotoxicity and La-responsiveness are functions of the same cells remains to be established.

Agglutinins↗

Natural cytotoxicity of human Fc gamma-receptor-positive T lymphocytes after surface modulation with immune complexes.

In humans T cells with surface receptors for the Fc fragment of IgG (Fc gamma receptors) (TG cells) are effector cells in antibody-dependent cellular cytotoxicity (ADCC) and in natural cytotoxicity. While Fc gamma receptors are required to mediate ADCC, their role in natural cytotoxicity is unknown. To investigate this question, Fc gamma receptors on effector cells were modulated by interaction with IgG immune complexes. As a consequence of this modulation, TG cells lost most of their ADCC activity but retained a significant part of their natural killer activity. Thus, these experiments demonstrate that the cytotoxic mechanisms exerted by the same cell population can be dissociated experimentally. Furthermore, they suggest that the net natural cytotoxicity of normal human lymphocytes in certain effector cell-target cell combinations is the result of distinct types of reaction.

Antibody-Dependent Cell Cytotoxicity↗

Heterogeneity and mechanism of action of human natural killer lymphocytes: differential distribution of receptors for Helix pomatia haemagglutinin (HP receptors).

Neuraminidase-treated lymphocytes from the peripheral blood of normal human donors were fractionated on columns charged with Helix pomatia haemagglutinin (HP) coupled to Sepharose 4B. While lymphocytes lacking HP receptors (HP-) passed directly through the column (fraction I), lymphocytes with HP receptors (HP+) were subsequently eluted in two distinct fractions with two different concentrations of the competitive hapten N-acetyl-D-galactosamine (fraction II and III, respectively). The natural cytotoxicity of these lymphocytes to various tumour target cells (K562, T24, MANO, HCV29) was tested in a 51Cr release assay. Natural cytotoxicity was found in all three fractions recovered from the HP columns. In general, the cytotoxicity of the lymphocytes in fractions I and II was significantly enhanced over that of the unfractionated lymphocytes. Surface marker analysis and fractionation studies indicated that natural cytotoxicity in these target systems is exerted by both HP+ and HP- lymphocytes bearing Fc receptors for IgG. Since the HP receptor is considered to be a marker to T lymphocytes, the findings suggest that a significant fraction of these NK cells may be of T-cell lineage. The surface marker profiles of these NK cells are very similar to those of antibody-dependent K cells. Addition of Fab fragments of immunoadsorbent-purified rabbit antibodies to human immunoglobulin inhibited the natural cytotoxicity of HP-column-fractionated lymphocytes to various degrees, indicating that part but not all of it reflects antibody-dependent K-cell reactions. Since cytotoxicity in all three HP fractions was inhibitable in this way, the results suggest that immunoglobulin-dependent natural cytotoxicity may be displayed by both HP+ and HP- effector cells.

Agglutinins↗

Cell-mediated immunity in horses with sarcoid tumors against sarcoid cells in vitro.

Cell-mediated immunity in horses with sarcoid tumor against sarcoid antigens was studied in vitro by means of mixed lymphocyte tumor cell culture assay and lymphocyte-mediated cytotoxicity of 52Cr-labeled target cells. When Mc-1 sarcoid cells were used as stimulatory cells for peripheral blood lymphocytes in the mixed lymphocyte tumor cell assay, a clear difference in the kinetics of the generated lymphocytic proliferative response could be detected between sarcoid and control horses. With sarcoid horses, their proliferative maximum was reached 3 days earlier than that of the control horses, and at this time their proliferative activity was significantly increased over that of control horses. When normal allogeneic fibroblasts were used as stimulatory cells, no such difference between sarcoid and control horses could be seen. The cellular cytotoxicity of peripheral blood lymphocytes from sarcoid and control horses against Mc-1 cells or normal allogeneic fibroblast targets was very low. However, the mean cytotoxicity against Mc-1 was slightly increased for sarcoid horses as compared with that of control horses. In contrast, the cytotoxicity against allogeneic fibroblasts was slightly lower for sarcoid than for control horses. In contrast, the cytotoxicity against allogeneic fibroblasts was slightly lower for sarcoid than for control horses. Furthermore, it was shown that sarcoid horses, but not control horses, had a slightly but consistently increased cytotoxicity against Mc-1 cells as compared with that against normal allogeneic fibroblasts.

Animals↗

Cellular cytotoxicity in transitional cell carcinoma of the human urinary bladder - a summary.

The cytoxicity in vitro fo peripheral blood lymphocytes from patients with carcinoma of the urinary bladder (TCC-bladder) against allogeneic target cells from established cell lines was studied by the 51Cr-release assay. Lymphocytes from both untreated and treated TCC-bladder patients have a significantly elevated mean cytotoxicity to TCC-bladder target cells. Tumour cell destruction by lymphocytes from TCC-bladder patients shows a clear disease related specificity. In TCC-bladder patients a superimposed cytotoxicity exists, probably reflecting reactions against one or several tumour - associated antigens. In treated patients this cytotoxicity may be masked by higher incidence of cross reaction.

Carcinoma, Transitional Cell↗