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G R Pape

Publications and source records attributed to G R Pape.

At least 91 records · Page 5Linked to original sources
PubMed1983

Involvement of the cytotoxic/suppressor T-cell subset in liver tissue injury of patients with acute and chronic liver diseases.

So far, phenotypic and functional analyses of cytotoxic lymphocytes in viral hepatitis, as well as in primary biliary cirrhosis, have focused on circulating lymphocyte subpopulations, whereas their occurrence and distribution at the involved site, namely the liver, remain largely unknown. In the present study, monoclonal antibodies were used to characterize both circulating and liver-tissue-infiltrating lymphocyte subsets in acute cytomegalovirus hepatitis, in chronic B-virus hepatitis, and in primary biliary cirrhosis. Special emphasis was laid on the cytotoxic/suppressor T-cell subset. Total T cells were identified by the monoclonal antibody T411. The monoclonal antibody T811 was used to identify the cytotoxic/suppressor T-cell subset, which comprises virus-specific, altered self, and alloreactive cytolytic T lymphocytes and their precursors, a fraction of killer and natural killer cells. Furthermore, killer and natural killer cells were identified more specifically by the monoclonal antibody. HNK1. Irrespective of the number of cytotoxic/suppressor T cells in peripheral blood, these cells (T811 phenotype) were accumulated in the liver at the site of tissue injury. The preponderance of this lymphocyte subset at the site of tissue injury suggests an important role for these cells in the mechanism leading to tissue injury.

Adult↗
PubMed1981

Natural killer cell activity during treatment with fibroblast interferon.

Short- and long-term effects on natural cytotoxicity (NC) of i.v. administration of human fibroblast interferon (IFN--beta) was studied in patients with HBsAg positive chronic active hepatitis. Short-term kinetics demonstrated after a transient fall of NC a severalfold increase of NK activity after 24 hours. Long-term kinetics of NC revealed following features: The highest relative increase was seen during the initial phase of IFN--beta application. In all patients monitored so far the enhanced NK activity could be maintained during 2 to 4 weeks of therapy. Over a period of several weeks a gradual decrease of augmented NK activity was observed in spite of continued application of high doses of IFN--beta. These findings indicate that in-vivo administration of IFN--beta results in an augmentation of natural cytotoxicity in man. Prolonged treatment with IFN--beta seems to "exhaust" the NK cell system.

Adult↗
PubMed1980

Cytotoxicity in vitro of blood lymphocytes from bladder cancer patients and controls to allogeneic or autologous tumor cells derived from established cell lines or short-term cultures.

Blood lymphocytes from small groups of patients with transitional-cell carcinoma of the urinary bladder (TCC), clinical controls (CC) or healthy donors (HD) were tested for cytotoxicity in vitro by a 51Cr-release assay. The target cells were either from TCC or control tissue (long-term cultures) or were from short-term TCC cultures, kept in vitro for 10-20 transfer generations. When tested with allogeneic target cells from long-term cultures, TCC patients' lymphocytes tended to be more cytotoxic to TCC targets than to control targets. For the control lymphocytes this was not seen. A large proportion but not all of the cytotoxicity to these target cells was due to immunoglobulin-dependent cellular reactions, probably mediated by natural and disease-related antibodies of the lymphocyte donors, since it was significantly inhibited by Fab-fragments of rabbit antibodies to human immunoglobulin. Moreover, it was, to a large extent, mediated by lymphocytes with Fc-receptors for IgG. For seven of the TCC target cell cultures (two long-term and five short-term) autologous lymphocytes were also available for testing. While two patients were non-reactive to their own tumor cells, five reacted strongly in the autologous combinations. These autologous reactions were immunoglobulin-independent and were mediated by Fc-receptor-negative effector cells. In some instances, autologous cytotoxicity was accompanied by similar reactions to some of the allogeneic TCC targets but not to the allogeneic non-TCC control targets. On the basis of available information on HLA antigens in this material, the pattern of cross-reactions suggests that the cytotoxicity encountered in the autologous and in some of the allogeneic TCC-combinations may be the expression of antibody-independnet but specific CTL-mediated reactions, regulated by HLA. However, at the present stage of the investigation, other mechanisms must also be considered since the target cells from short-term TCC cultures were sometimes lysed by control lymphocytes in immunoglobulin-independent reactions. Whatever the explanation, the results show that the cytotoxicity observed in the in vitro systems is usually the net result of several different types of reaction. Which effector cell types and which mechanism of recognition will predominate in a given lymphocyte/target cell combination is greatly influenced by the nature and origin of the target cells used.

Aged↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1976

[Hairy cell leukaemia. I. Clinical features, cytochemistry, phagocytosis, establishment of permanent growing cell lines (author's transl)].

In seven patients the diagnosis of hair cell leukaemia (leukaemic reticuloendotheliosis) was confirmed cytochemically and histologically. Splenectomy, in six patients, apparently favourably influenced the course. Isoenzyme 5 of the acid phosphatase was demonstrated in the hairy cells of all patients. Reaction of alpha-naphthylacetate esterase was moderately positive in the hairy cells. Phagocytosis of latex and India-ink particles was demonstrated especially in tartrate-resistant cells of one patient. In two patients eight permanently growing cell lines were demonstrated from leucocytes and defined cytochemically. Capacity for phagocytosis of hairy cells and positive reaction of alpha-naphthylacetate esterase in the hairy cells suggest properties of monocytes. But it is not possible definitively to classify the hairy cells among B-cells or monocytes.

Acid Phosphatase↗
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↗
PubMed1975

[Experimental studies on proteolysis of hyaline membranes in vitro (author's transl)].

The incubation of lung tissue from premature infants with pulmonary hyaline membranes in fibrinolysis activating or fibrinolytically active solutions gave the following results. With streptokinase it was not possible to dissolve hyaline membranes (verification of the physiological lack of plasminogen in premature infants). The mean content of membranes after 24 hours showed to be 18.14 +/- 12.43% which almost corresponded to the control value of 20.24 +/- 10.54% after incubation in NaCl-solution. In comparison, solutions of plasmin, plasmin-activator or activator prepared from proactivator-plasminogen through activation with streptokinase led to a clear reduction in the membrane content, i.e. 11.00 +/- 6.50, 13.89 +/- 9.72, and 13.63 +/- 8.94%, respectively. A decrease in membranes equally strong to that after plasmin appeared after incubation for only 12 hours in trypsin (11.09 +/- 8.62%). Plasmin, plasmin-activator, and activator, but not streptokinase alone, caused also a considerable nonspecific proteolysis of the lung parenchyma which was equal to the trypsin effect, for example, with an only half as long incubation time. Since the lungs of premature infants contain the tissue activator of fibrinolysis we discuss the suggestion of Ambrus et al. (1974) to administer an injection of plasminogen to premature infants immediately after birth so that a spontaneous fibrinolysis can be favoured for developing hyaline membranes.

Chymotrypsin↗
PubMedDate not supplied

Differential expression of MHC class II subregion products on bile duct epithelial cells and hepatocytes in patients with primary biliary cirrhosis.

To study the expression of MHC Class II subregion gene products on biliary epithelial cells in primary biliary cirrhosis, frozen sections from liver biopsies of 15 patients with primary biliary cirrhosis were studied immunohistochemically using HLA-D subregion specific monoclonal antibodies L243 (HLA-DR), Leu10 (HLA-DQ) and B7/21 (HLA-DP). Patients with early stages of primary biliary cirrhosis showed expression of HLA-DP, HLA-DR and HLA-DQ subregion gene products on bile duct epithelial cells. In advanced stages of disease, no MHC Class II antigens or only HLA-DR and HLA-DP were expressed on bile duct cells. While normal hepatocytes did not express detectable amounts of MHC Class II antigens, hepatocytes from liver biopsies of four patients with primary biliary cirrhosis showed a distinct staining exclusively with monoclonal antibodies specific for HLA-DR. The expression of MHC Class II antigens on parenchymal cells was independent of a lymphocytic infiltration into the tissue. This study demonstrates that bile ductular cells, but not hepatocytes, express a full set of MHC Class II molecules at least during the early stages of primary biliary cirrhosis. We propose, therefore, that the expression of both HLA-DR and HLA-DQ subregion products on bile duct epithelial cells may be a necessary, although not sufficient, condition for the initiation of an autoimmune process leading to the destruction of intrahepatic bile ducts in primary biliary cirrhosis.

Antibodies, Monoclonal↗