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Biomedical subjects

P Perlmann

Publications and source records attributed to P Perlmann.

At least 235 records · Page 13Linked to original sources
PubMed1978

Receptors for Helix pomatia A haemagglutinin (HP) on a subpopulation of human B cells.

Receptors for Helix pomatia A haemagglutinin (HP) have earlier been found on neuramidinase treated T-lymphocytes in human peripheral blood. In contrast, the majority of the B-lymphocytes, characterized by surface bound IgM and/or IgD(SIg)lack these receptors. Double marker experiments with fluorochrome labelled reagents have now shown that a minor fraction (3--24%) of the IgM/d bearing lymphocytes in normal human blood also have HP-receptors. These HP+ B-cells constitute approximately 1% of the HP+ lymphocytes in adult blood. Fractionation on HP-Sepharose columns showed that the HP+ B-cells are readily eluted with buffer containing 0.1 mg N-acetyl-D-galactosamine. In contrast, the majority of the HP+-SIg--cells require higher concentrations of the competing hapten for elution (1 mg D-Ga1NAc/ml buffer). This indicates that the HP-receptors on these B-cells differ qualitatively or quantitatively from those on the majority of the T-cells. Previous findings of HP-receptors on the SIg+ leukaemic cells in the blood of patients with chronic lymphocytic leukemia suggested that these structures are expressed on an immature variety of B-cells. This assumption is favoured by the present finding that approximately 80% of the lymphocytes with surface bound IgM/D in cord blood also have HP-receptors. Therefore, the HP-receptors seems to fall in the category of differentiation markers and constitutes a useful tool for characterization and separation of human lymphocytes within both the T- and the B-compartments.

Adult↗
PubMed1978

Specificity of Fc-receptors on lymphocytes and monocytes for guinea-pig IgG1 and IgG2: phagocytosis of erythrocytes.

The capacity of guinea-pig IgG1 and IgG2 antibodies to induce lymphocyte (K-cell) mediated lysis or monocyte/macrophage mediated phagocytosis of erythrocytes was studied with both human and guinea-pig effector cells. For both species, induction of K-cell mediated lysis was restricted to IgG2 whereas both IgG1 and IgG2 could induce monocyte/macrophage mediated phagocytosis. In competitive inhibition experiments, only complexed IgG2 inhibited lysis mediated by K-cells. The results suggest that the fc-receptors on K-cells only recognize IgG2. In contrast, complexes of both subclasses inhibited phagocytosis by human monocytes, regardless of the subclass of the inducing antibodies. Inhibition of guinea-pig macrophage mediated phagocytosis by IgG2 complexes was also independent of the inducing antibody. Hence, Fc-receptors common for IgG1 and IgG2 seem to be involved in themonocyte/macrophage mediated effector reaction. Free IgG1 was significantly less ingibitory than free IgG2 for human monocytes and hardly at all for guinea-pig macrophages. However, free IgG2, which was cytophilic for these cells, was more aggregated than IgG1. Thus, both molecular structure and state of aggregation determine interaction of IgG with cellular Fc-receptors.

Animals↗
PubMed1977

K cell mediated lysis of cultured colon carcinoma and urinary bladder carcinoma cells induced by monospecific antisera against carcinoembryonic antigen (CEA) and two CEA-related normal glycoproteins.

Antibody dependent lymphocyte (K cell) mediated lysis of tumor cells in vitro was used to assay for cell surface associated carcinoembryonic antigen (CEA) and two CEA-related normal tissue components, "normal glycoprotein" (NGP) and biliary glycoprotein I (BGP I). Three tumor cell lines were used as target cells. These were HT-29, colon carcinoma, T-24, urinary bladder transitional cell carcinoma and Mel-1, malignant melanoma. To induce lysis we used the IgG-fraction of specific rabbit and monkey anti-CEA sera and of specific rabbit anti-NGP and anti-BGP I sera, respectively. Purified human lymphocytes were used as effector cells. HT-29 was efficiently killed by low concentrations of rabbit anti-CEA and less efficiently by monkey anti-CEA. T-24 and Mel-1 were not lysed by anti-CEA, HT-29 and T-24 were lysed by low concentrations of anti-BGP I. In contrast only HT-29 was lysed by anti-NGP. Only a fraction of the tumor cells was killed by the different antisera although kinetic studies showed that the lytic reaction was complete well before the end of the eighteen hour incubation period used in the assay. Anti-CEA and anti-BGP I gave 30-40% corrected lysis of HT-29. With anti-NGP the corresponding figure was 10-20%.

Adenocarcinoma↗
PubMed1977

Complement-dependent cytotoxicity against hepatoma cells mediated by IgM antibodies in serum from tumor-bearing rats.

Complement-dependent cytotoxic antibodies in syngeneic serum from rats carrying transplanted aminoazo dye-induced hepatomas (D23 and D33) and from rats immunized with irradiated tumor cell or homogenates were studied by a short-term 51Cr release assay. The tumor-bearer sera (TBS) were subjected to chromatography on unsolubilized protein A and Sepharose 4B. The cytolytic activity of D23 TBS was recovered in the IgM molecular weight region, whereas no such activity was obtained in the IgG fraction. As judged from immunodiffusion experiments, the IgM molecular weight fraction did not contain any aggregated or complexed IgG. Moreover, in immunofluorescence tests against viable hepatoma cells, using a specific anti-rat IgG conjugate, the TBS were negative. Cross-testing of D23 and D33 TBS against the two hepatomas and cross-absorption of the sera with tumor plasma membranes revealed no tumor specificity in these cytotoxicity reactions. Furthermore, neither fetal nor early postnatal liver cells could absorb out the activity. Absorptions with adult liver plasma membranes, however, abrogated the cytotoxic activity, and even more effective in this respect were homogenates from kidney and small intestine, thus indicating that the cytotoxic antibodies are directed against 'normal' adult antigen(s) present also in tissues other than liver.

Animals↗
PubMed1977

A new rat lymphocyte surface marker: characterization and separation of cells with receptors for Helix pomatia hemagglutinin.

Thirty-two percent of neuraminidase-treated DA rat spleen lymphocytes and 48% of lymph node lymphocytes possess receptors for Helix pomatia hemagglutinin (HP). Moreover, these HP-receptor-bearing cells can be separated from B cells by affinity chromatography on HP-Sepharose columns. The virtual absence of immunoglobulin (Ig) receptors and the close correlation with reported T-cell content of these lymphoid tissues suggest that HP-receptor lymphocytes are probably T cells and that HP may provide a convenient marker, for both the identification and the purification of rat T lymphocytes.

Agglutinins↗
PubMed1977

Immunological studies in ulcerative colitis. VIII. Antibodies to colon antigen in patients with ulcerative colitis, Crohn's disease, and other diseases.

Sera from patients with ulcerative colitis or Crohn's disease had elevated titers to colon antigen from germ-free rats significantly more often than sera from patients with gastroenteritis, irritable colon, non-gastrointestinal diseases, and healthy controls. Elevated anticolon titers in significant frequency were also found in patients with liver cirrhosis, urinary tract infections, and in polyposis coli and their relatives. Females with ulcerative colitis had, on an average, higher titers than men especially in the age group 30 years and over. In Crohn's disease the antibody titers often increased with time--as opposed to those in ulcerative colitis and non-gastrointestinal diseases. In conjunction with results published earlier, the present work supports the assumption that the antibodies in ulcerative colitis patients react with antigenic determinants distinct from those recognized by the colon antibodies present in other groups, including patients with Crohn's disease and polyposis.

Adolescent↗
PubMed1977

Interactions between human lymphocytes and paramyxovirus-infected cells: adsorption and cytotoxicity.

The capacity of human lymphocytes to adhere to paramyxovirus-infected monolayers and their capacity to kill paramyxovirus-infected cells was investigated. A large fraction of human lymphocytes was found to adhere firmly to the paramyxovirus-infected monolayers. Predsorption of lymphocytes on mumps virus-infected cells impaired their adsorption to a second cell monolayer of the same type. The cytotoxic activity of lymphocytes against mumps virus-infected cells was also reduced after predsorption on mumps virus- or Newcastle disease virus-infected (NDV) cell monolayers. Exposure of lymphocytes to trypsin did not significantly decrease either adsorption or cytotoxicity. Pretreatment of lymphocytes with neuraminidase (NANase) partly inhibited adsorption whereas cytotoxicity was not decreased. Cell fractionation experiments after rosetting of the lymphocytes with sheep erythrocytes (E) indicated that T cells were equally or better adsorbed than "non-T" cells. Taken together with previous experiments which showed that the majority of T lymphocytes are not cytotoxic against mumps virus-infected cells these results suggest that adherence of lymphocytes to infected cells and cytotoxicity may be unrelated phenomena.

Antigens, Viral↗
PubMed1976

Analysis by a plaque assay of IgG- or IgM- dependent cytolytic lymphocytes in human blood.

When monolayers of bovine erythrocytes (Eb) were exposed to purified human blood lymphocytes and either IgG or IgM fractions of rabbit anti-Eb serum, clear zones (plaques) appeared when Eb had been lysed by antibody-dependent effector cells (K cells). IgG-dependent plaque formation was complete by 20 h of incubation, while the IgM-dependent reaction required 40 h. The estimated minimal numbers of plaque forming cells (PFC) were 5.6% (IgG) and 2.0% (IgM) of the added lymphocytes. Inhibition experiments with human IgG or IgM indicated that different immunoglobulin receptors on the effector cells were involved in the two systems. In the IgG system, approximately 50% of the PFC had complement receptors and approximately 30% receptors for Helix pomatia A hemagglutinin (HP). In the IgM system, less than 10% of the PFC had complement receptors, while approximately 60% had HP receptors. The results suggest that a subset of human T cells had IgM-dependent K-cell potential. These cells are different from the majority of the IgG-dependent K cells.

Binding Sites↗
PubMed1976

Fractionation of human T lymphocytes on wheat germ agglutinin-sepharose.

T cells from human peripheral blood was purified by fractionation on columns charged with human immunoglobulin and rabbit anti-human immuno-globulin. When assayed with 125I- or fluorescein isothiocyanate-labeled wheat-germ agglutinin (WGA), a weakly binding and a strongly binding subpopulation could be distinguished. These T-cell subpopulations were fractionated on columns charged with WGA, convalently bound to Sepharose 6MB. The cells responding to the mitogens leukoagglutinin from Phaseolus vulgaris and concanavalin A were enriched in the strongly binding subpopulation (approximately 20% of the T cells) while they were depleted from the weakly binding subpopulation.

Binding Sites↗
PubMed1976

Differential cytotoxicity of activated lymphocytes on allogeneic and xenogeneic target cells. III. Species specificity of lymphocyte target cell recognition in vitro.

Cytotoxic effector lymphocytes were produced by stimulation of human peripheral blood or mouse spleen lymphocytes with PPD, PHA or PWM in vitro. The specificity of the lymphocyte target cell interaction was studied in vitro. The specificity of the lymphocyte target cell interaction was studied by adsorption of effector cells on various target cell monolayers. The cytotoxic activity of human lymphocytes against 51Cr-labeled human or monkey target cells was reduced by prior incubation on primate monolayers while it was much less affected by incubation on rodent monolayers. Conversely the cytotoxicity of mouse lymphocytes against mouse L cells was strongly reduced by absorption on mouse or rat monolayers but significantly less by that on human monolayers. This suggests that this species-specific cytotoxicity reflects recognition by activated lymphocytes of some common surface structures present only on cells of the species of the effector cell donor, or on cells from phylogenetically closely related species. Lymphocyte-mediated cytotoxicity against xenogeneic target cells was studied after stimulation with PWM. The capacity of human lymphocytes to kill 51Cr-labeled mouse cells was reduced by adsorption on either rodent or primate monolayers. Conversely, prior incubation of mouse lymphocytes on either human or mouse monolayers led to inhibition of 51Cr release from labeled Chang cells. These results suggest that the mitogen-activated effector cells which are cytotoxic for more distantly related xenogeneic target cells have receptors for structures which are common for these cells and for target cells of the species of the lymphocyte donors.

Animals↗
PubMed1976

Purification, fractionation and assay of antibody-dependent lymphocytic effector cells (K cells) in human blood.

In this article we present methods for the purification and fractionation of human blood lymphocytes, which have been used in our laboratory to characterize antibody-dependent cytotoxic effector cells (K cells). The assay system consists of highly purified lymphocytes, 51Cr-labelled chicken erythrocytes (Ec) and IgG rabbit anti-Ec in high dilutions. Various ways of comparing K-cell potentials of different lymphocyte preparations in this system are discussed. When purified lymphocytes are partially depleted (60-85% depletion) of cells forming rosettes with sheep erythrocytes (E+ cells), the K-cell activity of the depleted fraction is increased, indicating the the majority of the E+ cells are inactive in this assay. Depletion of EAC-rosette-forming cells shows that most or all K cells have complement receptors. For depletion of B cells, the lymphocytes may be passed through glass bead columns, charg ed with F(ab')2 fragments of human IgG and F(ab')2 fragments of rabbit antibodies to the F(ab')2 part of human IgG. These columns give high yields of B-cell depleted fractions. These preparations are rich in E+ cells and contain approximately 80% of the Fc-receptor lymphocytes which form rosettes with bovine erythrocytes, coated with IgG antibodies. Their K-cell activity is unchanged or slightly elevated, indicating the mature B cells, i.e. SIg+ cells, have little or no K-cell activity. In contrast, passage of the lymphocytes through immune complex columns (ovalbumin/anti-ovalbumin) leads to approximately 70% depletion of Fc receptor-bearing cells, while most of the B cells (SIg+ cells) pass through the columns. The relative frequency of E+ cells in the passed fraction frequently shows a slight reduction. These preaparations have a very low K-cell activity, indicating that K cells are lymphocytes with Fc receptors of relatively strong avidity.

Antibody-Dependent Cell Cytotoxicity↗