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E W Fuson

Publications and source records attributed to E W Fuson.

18 recordsLinked to original sources
PubMed1985

Antibody-dependent cell-mediated cytotoxicity by human lymphocytes: a regulatory role for the sheep red blood cell receptor.

Antibody-dependent cell-mediated cytotoxicity (ADCC) is a cytolytic mechanism whereby unimmunized lymphoid cells lyse antibody-sensitized target cells. The cells mediating ADCC are referred to functionally as killer cells (K cells). K cells are a heterogeneous population of lymphocytes based on cell membrane marker criteria but may be morphologically homogeneous. It is well established that K cells must have an Fc receptor (FcR) appropriate for the class of target cell-bound antibody, and that physical interaction between the K cell's FcR and the Fc portion of target cell-bound antibody is required for the initiation of lysis. Relatively little is known about the regulatory mechanisms presumed to exist and modulate ADCC reactions. We have made 2 observations that led us to investigate the possibility that the sheep erythrocyte (SRBC) receptor (ER) on human cells might be involved as a regulator of ADCC. First, SRBC are more efficiently lysed by human lymphocytes than are other erythrocyte target cells, and second, although nonsensitized bystander cells are usually not lysed during ADCC reactions, SRBC are consistently lysed. Removal of E-rosetting capacity of lymphocytes by trypsin treatment selectively decreases lysis of IgG sensitized SRBC. Furthermore, lysis of nonsensitized bystander SRBC is also inhibited by trypsin treatment of effector cells. ADCC is also decreased by blocking the ER with simple sugars or monoclonal antibody so that E-rosettes are inhibited. In contrast to trypsin treatment, which selectively inhibits lysis of SRBC, ER-specific monoclonal antibody and simple sugars decrease cytolysis against all target cells tested.

Animals↗
PubMed1984

Immobilized IgG-aggregate-induced cytolytic activity of lymphocytes from patients with rheumatoid arthritis.

T-depleted lymphocytes can lyse nonsensitized target cells subsequent to interacting with immobilized IgG-aggregate, while T cells from healthy individuals can suppress this cytolytic response. In the present study we have compared the activity of non-T effector cells and T suppressor cells from the peripheral blood of healthy individuals with that of cells from the peripheral blood and synovial fluids of patients with rheumatoid arthritis (RA). Unlike peripheral blood lymphocytes (PBL) from healthy donors, which were never lytic without removing T suppressor cells, PBL from RA patients were occasionally active without removing T cells; lymphocytes from joint fluids were almost always active. The lytic response of RA joint fluid lymphocytes could be suppressed by T cells from autologous or healthy donor peripheral blood, thus suggesting that the suppressor cell which regulates this lytic mechanism might be defective or absent in joint fluids of RA patients.

Arthritis, Rheumatoid↗
PubMed1982

Nonspecific human lymphocyte-mediated cytotoxicity induced by immobilized IgG aggregate: regulation by suppressor cells.

Normal human lymphocytes lyse a variety of erythrocytes when effector cells and target cells are incubated on immobilized, normal human IgG aggregates (10). Lymphocyte-mediated cytolysis induced by immobilized aggregate requires an overnight incubation with adherent mononuclear cells. This study was carried out to determine whether preincubation with adherent cells effects the activation of a cytolytic cell or inactivation of a suppressor cell. It was determined that a suppressor cell function is inactivated, and the suppressor cells were characterized as T gamma and T mu lymphocytes.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1981

Murine T cells that lyse antibody-sensitized target cells. III. Contribution of Thy 1-Bearing cells to the lytic activity of normal spleen.

Murine spleen cells were analysed for their capacity to lyse 51Cr-labelled antibody-sensitized erythrocytes and a human lymphoma cell line. Incubation of spleen cells with iron powder followed by removal of iron-containing cells with a magnet significantly decreased the lytic capacity of the remaining cells against erythrocyte target cells. However, substantial cytotoxicity remained in the relatively phagocyte-depleted population. Both antibody-sensitized erythrocytes and tumour cells were lysed by phagocyte-depleted effector cells. However, more spleen cells were required to lyse nucleated target cells than were required to produce comparable lysis of the erythrocytes. Such phagocyte-depleted spleen cells were subsequently treated with three different antisera containing specificities for thymus-dependent antigens and a monoclonal IgM anti-Thy 1.2 in the presence of complement. The remaining viable cells were recovered and tested as effector cells. All four reagents in the presence of complement caused an inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC) that was proportional to the percentage of T cells eliminated. However, the antisera also inhibited ADCC in the absence of complement, even when the cells were trypsinized following the antiserum treatment to remove attached antibodies. On the other hand, treatment of spleen cells with the monoclonal IgM anti-Thy 1.2 followed by trypsin treatment did not inhibit ADCC unless complement was added. Thus, with the latter reagent, decreased ADCC could be ascribed to elimination of T cells and not immune complex inhibition. Cells bearing Thy 1.2 accounted for approximately half of the lytic activity of phagocyte-depleted spleen cells against antibody-sensitized target cells.

Animals↗
PubMed1981

Antibody-dependent cell-mediated cytotoxicity by human lymphocytes. II. Comparison with polymorphonuclear leukocytes against erythrocyte and nucleated target cells.

Human peripheral blood lymphocytes were compared to neutrophils with respect to their cytotoxic activity against IgG-sensitized erythrocytes (ox; ORBC) and nucleated (Raji) target cells in vitro. Overall, neutrophils were more efficient than lymphocytes in lysing erythrocytes, but lymphocytes were more efficient in lysing Raji cells. The antibody concentrations producing maximal levels of lysis against erythrocyte target cells were similar for both kinds of effector cells and guinea pig complement; however, in order to obtain Raji cell lysis mediated by neutrophils at a level comparable to that produced by lymphocytes a higher concentration of antibody was required. Another difference found between the lytic activity of these effector cell populations was kinetics of lysis against erythrocyte target: a 15 min lag phase was consistently observed only with neutrophil effector cells. Both effector cells lyse Raji cells with similar kinetics and no lag phase. Lysis by lymphocytes and neutrophils was directly proportional to the effector:target cell (E:T) ratio against both target cells. The effector cells were similarly inhibited from lysis of erythrocytes by IgG aggregate, but neutrophil lysis of Raji cells appeared to be more sensitive to inhibition. The neutrophils did not lyse nonsensitized bystander cells, and lymphocytes lysed sheep erythrocyte bystander cells only.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1980

Different divalent cation requirements for binding IgM complexes to lymphocytes and macrophages.

We have found that Mg++ supports IgM complex binding to mouse lymphocytes but not to macrophages. In contrast, Ca++ supports IgM complex binding to macrophages but not lymphocytes. IgG complex binding to both lymphocytes and macrophages is divalent cation independent. These findings allow one to distinguish IgG from IgM binding and macrophage from lymphocyte IgM complex binding by their differential divalent cation requirements.

Animals↗
PubMed1979

Antibody--antigen complex stimulated lysis of non-sensitized sheep red cells by human lymphocytes. I. Requirements for IgG complexes.

IgG antibody--antigen complexes stimulated lysis of non-sensitized sheep erythrocytes (SRBC) by normal human peripheral blood lymphocytes (PBL). Heat-aggregated human IgG, rabbit IgG-ovalbumin complexes and rabbit IgG-sensitized ox erythrocytes (ORBC) were effective in the induction of SRBC lysis by PBL. However, IgM-sensitized ORBC and IgM-complement-sensitized ORBC were ineffective. As only SRBC and not ORBC or chicken erythrocytes (CRBC) were lysed under identical experimental conditions, it is conceivable that the SRBC receptor present on the T cell is involved. Furthermore, 45% inhibition of lysis was obtained by pretreating the effector cells with anti-human thymocyte globulin (ATG) and complete inhibition was obtained by adding SRBC stroma to the reaction mixture. The requirement for the inclusion of IgG complexes and the absence of specific anti-target cell antibody distinguish this reaction from natural cell-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC). Immune killer T cells would not appear to be responsible as eight different donors were used and none of these were cytotoxic to SRBC in the absence of IgG complexes. The induction of this cytotoxic reaction appears to require the recognition and interaction by the effector cells of two separate molecular entities, i.e. the SRBC membrane by the T cell and the IgG Fc region by an IgG-Fc receptor-bearing cell.

Animals↗
PubMed1977

Antibody-dependent cell-mediated cytotoxicity in the Moloney sarcoma virus system: differential activity of IgG and IgM with different subpopulations of lymphocytes.

Antibody-dependent cell-mediated cytotoxicity in the Moloney sarcoma virus (MSV) system was evaluated in terms of the differential ability of IgG and IgM from MSV regressor animals to induce cytotoxicity by lymphocytes from lymph node, spleen, and thymus. The cell-mediated cytotoxicity induced by both IgM and IgG was specific for target possessing the appropriate virally determined cell surface antigen(s). IgM induced cytotoxicity by lymphocytes from all the organs tested. However, differences in magnitude and efficiency were revealed. Lymph node cells and thymocytes were most efficient against IgM-coated target cells. Against IgG-sensitized target cells, spleen and lymph node cells were about equally active, but thymocytes were inactive. Cortisone treatment of the donors of effector cells revealed that the cortisone resistant subpopulation of thymocytes, 2 days after cortisone injection, exhibited an increased cytotoxicity against target cells treated with unfractionated antiserum and its IgM fraction. This subpopulation of thymocytes was also cytotoxic against IgG-coated target cells. At 12 days after cortisone injection, the repopulated thymus showed little change in activity, compared to control thymus, against antibody-coated target cells.

Animals↗