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Biomedical subjects

S Meuer

Publications and source records attributed to S Meuer.

At least 55 records · Page 3Linked to original sources
PubMed1990

Lymphocytes from hepatic inflammatory infiltrate kill rat hepatocytes in primary culture. Comparison with peripheral blood lymphocytes.

In the last few years it has become possible in the liver to isolate lymphocytes from inflammatory infiltrates and to culture them in vitro. Most of the lymphocyte clones obtained are CD 8+ cytotoxic cells, but interactions between these lymphocytes and hepatocytes in primary culture have not been analysed previously. In this study, cloned human T lymphocytes from liver biopsies and from the peripheral blood of patients with chronic hepatitis B or primary biliary cirrhosis, after phenotypical and functional characterization into CD 8+ or CD 4+ cytotoxic lymphocytes, were activated in an antigen-independent fashion by adding either anti CD 3 or anti CD 2/R-3 monoclonal antibodies to the cell suspension. The activated cells were then coincubated with rat hepatocytes in primary culture. The killing capacity of the activated lymphocytes was monitored by light and electron microscopy and by measurement of lactic dehydrogenase (LDH)-release into the culture medium. It was found that cytotoxic CD 8+, but not CD 4+ helper lymphocytes very effectively killed hepatocytes. The killing effect was dependent on the time of cocultivation and on effector-target (E/T) ratio. Total breakdown of the hepatocyte monolayer was achieved after 10-20 h coculture and at an E/T ratio of 10 to 1. As LDH-release in the culture medium reached about 80% of the total LDH-content, most of the hepatocytes were lysed by activated lymphocytes. Cytotoxic activity of clones obtained from different biopsies was comparable with that of clones from peripheral blood. Hepatocytes in primary culture seem to be very sensitive to the killing capacity of activated cytotoxic lymphocytes.

Animals↗
PubMed1990

Hepatitis B vaccination and interleukin 2 receptor expression in chronic renal failure.

Only 50 to 60% of dialysis patients develop anti-HBs antibodies following hepatitis B vaccination. The nonresponder state correlates with impaired monocyte function, decreased interleukin-2 (IL-2) production of T cells, and an upregulation of the IL-2 receptor system. In the present study we examined anti-HBs production after hepatitis B vaccination and the in vitro expression of IL-2 receptors in nondialyzed patients with various degrees of chronic renal failure. Forty-four patients with impaired renal function were immunized with 2 micrograms recombinant hepatitis B vaccine and boostered after one and six months. Prior to the first injection IL-2 receptor expression of activated T cells was studied by an in vitro proliferation assay. Sixty-four healthy subjects served as controls. After completion of the third vaccination 55.0% of the patients acquired antibody titers greater than 10 U/liter. The seroconversion rate did not differ between patients with lower (less than 3.5 mg/dl) and higher (greater than 3.5 mg/dl) creatinine levels. In nonresponders IL-2 receptor expression (stimulation index, SI = 10.09 +/- 1.80) was elevated compared to healthy controls (SI = 4.62 +/- 0.35, P less than 0.002) or patients who responded with a high antibody titer (greater than 50 U/liter, SI = 3.12 +/- 0.43, P less than 0.001). Patients who produced low antibody titers (less than 50 U/liter) also presented with enhanced IL-2 receptor expression. These data show that an impaired antibody production following hepatitis B vaccination and an enhanced IL-2 receptor expression of T cells may already be present in early stages of chronic renal failure.

Antibody Formation↗
PubMed1990

Association of CD2 and T200 (CD45) in mouse T lymphocytes.

A monoclonal antibody (mAb 12-15) reactive with the mouse CD2 was found to co-precipitate a high-molecular-weight glycoprotein from mouse thymocyte, splenic lymphocyte, Con A blast, and T cell tumor detergent lysates which was identified as the leukocyte common T 200 glycoprotein (CD45). The reactivity was specific for CD2 since antibodies to CD3 did not co-precipitate the T200 glycoprotein. mAb 12-15 did not react with immunoaffinity-purified T200 glycoprotein, ruling out the possibility that the antibody detected a cross-reactive epitope. Biochemical data indicated that the association of CD2 with T200 was not generated during lysis of the cell and that the molecular complex was non-covalently linked since it could be destroyed by high salt washing or boiling in SDS. Distribution analysis in Triton X114-H2O revealed that, in contrast to free T200 molecules, the complexed T200 was enriched in the detergents phase. To investigate the CD2-T200 association in more detail at the cell surface, modulation of CD2 and T200 was studied. Modulation could be induced on Con A blasts by monoclonal antibodies followed by cross-linking with a FITC-conjugated second antibody. Within 24 h the expression of CD2 or T200 was reduced to approximately 10-20% of the initial value on the majority of cells. However, two-color fluorescence showed that modulation of CD2 did not lead to co-modulation of CD3 or T200. A possible physiological role of CD2-T200 complexes is discussed.

Animals↗
PubMed1989

Allogeneic mixed lymphocyte reactions during a second round of ontogeny: normal accessory cells did not restore defective interleukin-2 (IL-2) synthesis in T cells but induced responsiveness to exogeneous IL-2.

The T-cell-accessory-cell interaction in mixed lymphocyte cultures was investigated in 25 patients following autologous bone marrow transplantation (ABMT) using autologous bone marrow treated in vitro with the cyclophosphamide derivative ASTA Z 7557. In a previous study using the same group of patients, T cells failed to synthesize interleukin-2 (IL-2) and proliferate in response to CD3- and CD2-mediated stimuli even in the presence of exogenous IL-2. To investigate whether this defect in IL-2 synthesis and proliferation was caused by defective cell-to-cell interactions, we analyzed mixed lymphocyte reactions (MLR) using T cells and irradiated non-T cells. When normal T cells from 10 different healthy subjects were challenged with allogeneic normal non-T cells, IL-2 production and proliferation were observed. In contrast, when normal T cells were cultured with non-T cells derived from patients found between 20 and 330 days after ABMT, no IL-2 secretion and no proliferative responses could be seen. The addition of lymphokines such as interleukin-1 (IL-1), interleukin-3 (IL-3), tumor necrosis factor (TNF), granulocyte-macrophage colony stimulating factor (GM-CSF), and interferon-gamma (IFN-y) did not improve the reactions. Furthermore, when patients' T cells were incubated with normal, irradiated non-T cells, defective IL-2 synthesis or proliferative response was obtained. However, when IL-2 was added to these cultures, an improvement in proliferative reactions was observed. Taken together, these new data provide additional evidence that T cells early in ontogeny possessed an intrinsic defect in IL-2 synthesis and that physical cell-to-cell contact between patients' T cells and allogeneic accessory cells induced functional responsiveness to exogeneous IL-2.

Antigen-Presenting Cells↗
PubMed1989

T-cell ontogeny after autologous bone marrow transplantation: failure to synthesize interleukin-2 (IL-2) and lack of CD2- and CD3-mediated proliferation by both CD4- and CD8+ cells even in the presence of exogeneous IL-2.

T cells generated during a second round of ontogeny after autologous bone marrow transplantation (ABMT) represent a unique model of early T-cell ontogeny in an autologous situation. Since grafted bone marrows were pretreated in vitro with the cyclophosphamide derivative ASTA Z 7557, circulating T cells had to be regenerated from reinfused hematopoietic progenitor cells. The T-cell population derived from 25 patients post-ABMT was phenotypically characterized: an increase in CD8+ cells, a low percentage of CD4+ cells, and a median of 12% CD56+ (NKH1+) cells were found. When the T cells were stimulated with phytohemagglutinin (PHA) and phorbol myristate acetate (PMA), defective interleukin-2 (IL-2) secretion was observed. In addition, proliferative responses of the T cells after activation through the antigen-receptor-dependent CD3 pathway, through the CD2 dependent alternative T-cell pathway, and by the lectin PHA were investigated. Despite the presence of CD2, CD3, alpha/beta chains of the T-cell receptor, and CD25+ IL-2 surface receptors, abnormal proliferative responses were obtained even in the presence of exogeneous IL-2. In experiments where the T-cell population was separated into CD4+ cells and CD8+ cells, both the CD4- and CD8+ subsets were unable to respond to activating and proliferating signals. Thus, T cells at early stages of ontogeny not only possess an intrinsic defect in IL-2 synthesis but, in addition, were unable to express functional IL-2 receptors in response to mitogenic stimuli.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

[Secondary immune deficiency in renal failure exemplified by hepatitis B vaccination].

In dialysis patients the immune response to hepatitis B-vaccination is greatly impaired. In vitro the non-responders show a failure of the monocytes to support the process of primary T-cell activation. This defect results in a lack of interleukin 2-production and an enhanced sensitivity of the interleukin-2 receptor system. Addition of low doses of interleukin-2 fully reconstitutes the deficient immune response in vitro. Furthermore, the local application of low dose interleukin-2 during a standard vaccination with 40 micrograms hepatitis B-vaccine normalizes the non-responder state in vivo.

Hepatitis B↗
PubMed1988

Identification of a CD2- CD3+ T cell receptor-gamma+ peripheral blood lymphocyte subpopulation.

We have identified, in a healthy individual, a sub-population of human peripheral lymphocytes which surface express a CD3-TCR-gamma complex recognized by anti-Ti gamma A mAb, while being unreactive with a phycoerythrin-conjugated anti-CD2 antibody with T11/1 specificity. Further immunofluorescence analyses performed on uncultured cells indicated that such a putative CD2-CD3+ phenotype was restricted to a fraction of those T lymphocytes which carry a surface receptor of the "second family" (gamma/delta). The actual lack of CD2 expression was confirmed by a subsequent series of cloning experiments which showed that none of the three well characterized CD2 epitopic clusters, namely T11/1, T11/2, and T11/3, were detectable on the surface of the relevant cells. The cultured CD2-, CD3+/TCR gamma + lymphocytes were found to display, as well as their CD2+ counterparts, both non-MHC-restricted cytotoxic function and proliferative responses induced via the gamma receptor complex. In contrast, the proliferative capacity of the CD2-, CD3+/TCR-gamma + cells observed in a culture system designed for in vitro expansion of lymphocytes with undefined specificity was extremely limited. This may relate to an impaired interaction of the CD2- cloned lymphocytes with lymphocyte function-associated (LFA)3+ irradiated cells present in the feeder layer. Further characterization of such minor CD2- T lymphocytes subsets may help to better understand the biologic relevance of the CD2/LFA3 pathway of cell-cell interaction.

Adult↗
PubMed1988

Tissue distribution of the T cell activation antigen Ta1. Serological, immunohistochemical and biochemical investigations.

The recently described Ta1 antigen is expressed by activated T cells in vitro and in vivo, as observed in patients with certain immune-mediated diseases, such as multiple sclerosis. In this paper we report on the tissue distribution of the Ta1 antigen. Serological testing of human tumour cell lines and immunohistochemical analysis of human tissue sections revealed a reactivity of the anti-Ta1 antibody with normal and malignant tissues of the upper gastro-intestinal tract, the biliary tract, exocrine pancreas and kidney. SDS-PAGE analysis of immunoprecipitates from 125I-labelled cells, employing the anti-Ta1 antibody, yielded a 113-115 kD band from three serologically Ta1 positive tumour cell lines, from a serologically Ta1 negative human EBV-transformed B lymphoblastoid cell line, from peripheral blood mononuclear cells (PBMC) and, as previously described, a 105 kD band from PHA activated T cells (Fox et al., 1984). After endoglycosidase F treatment similar bands of 85 kD were precipitated from activated T cells and from tumour cell lines. It is therefore likely that very similar glycoproteins, which differ only modestly in the size of carbohydrate chains, bear the Ta1 epitope on Ta1 positive tissues.

Antibodies↗
PubMed1987

Suppressive effects of C3b on monocyte-dependent T cell proliferation.

The effect of C3b treatment of human monocytes on secondary antigen-dependent T cell response was studied. When antigen-specific T cell blasts were cultivated together with C3b-treated monocytes the proliferative response was inhibited in a dose-dependent fashion. This suppressive effect was specific for C3b because heat-inactivated C3b or buffer alone had no influence on T cell proliferation. In part, this suppressive effect is mediated through a C3b-induced decreased expression of class II antigens on the surface of treated monocytes, but another suppressive mechanism exists because the C3b pretreatment of monocytes also led to an inhibition of the proliferative response in a class II antigen-independent T cell proliferation system. In addition to the C3b data, our finding that treatment of monocytes with C3d resulted in a lower T cell proliferation, while C3c has no effect, suggested that C3d, which could be generated from C3b in the culture, may induce the second inhibitory mechanism.

Cells, Cultured↗
PubMed1987

The "erythrocyte receptor" of T-lymphocytes and T11 target structure (T11TS): complementary cell interaction molecules involved in T-cell activation.

The CD2 or T11 glycoprotein on T-lymphocytes is the receptor for both sheep and human erythrocytes in the formation of spontaneous ("E"-)rosettes. Recent evidence employing monoclonal anti-T11 antibodies suggested that T11 is also a signal transducing molecule with a function in T-cell activation. The present report summarizes the identification of T11 target structure (T11TS), a natural ligand of T11, and its biochemical and functional characterization. T11TS is defined by a mAb to sheep erythrocytes that completely blocks their binding to CD2. It is a glycoprotein of 42 kDa MW expressed on all types of blood cells and some other tissues. While the anti-T11TS mAb used is specific for sheep cells, an antiserum raised to purified T11TS also blocks human autologous E-rosetting. Evidence is presented that the human lymphocyte function associated antigen (LFA)-3, which had recently been shown to be the likely human ligand of CD2, is the structural and functional human homologue of T11TS. Functional studies on T-cell activation employing sheep erythrocytes as one ligand of CD2 indicate that binding of T11TS to the E-receptor provides one of the signals required for T-cell activation through the CD2 molecule.

Animals↗
PubMed1986

Definition of discrete signals involved in human T-cell activation.

Mitogenic activities of monoclonal antibodies directed at defined receptor structures expressed on the surface of mature human T lymphocytes were employed to study, in detail, signals involved in primary T-cell activation. Based on differential requirements for stimulation, two discrete pathways of human T-cell activation can be defined: the antigen-induced mode of activation initiated through the Ti-T3 antigen-receptor complex and an alternative pathway which can be triggered by monoclonal antibodies directed at the T11 glycoprotein. Perhaps more importantly, the approach taken here allows the definition of stable intermediate cellular stages within the activation cascade and, thus, to analyze the signalling capabilities of individual receptor molecules.

Adult↗
PubMed1986

Expression of Ia-antigens on guinea pig Kupffer cells. Studies with monoclonal antibodies.

The expression of the Ia-antigen on guinea pig Kupffer cells was studied employing two monoclonal antibodies against two different determinants of the Ia-molecule. The study was performed in situ on liver sections and on isolated highly purified Kupffer cells kept in culture up to 6 days. The influence of guinea pig hepatocyte culture supernatant and of supernatants of phytohemoagglutinin (PHA)-stimulated human peripheral blood lymphocytes (PBL) on the Ia expression was measured. Immunofluorescence staining of cryostat sections revealed that the monoclonal antibodies used are able to detect Ia-antigens on liver macrophages in situ. The in vitro studies strongly suggest that all Kupffer cells are able to express Ia-antigens. The expression of Ia-antigens on Kupffer cells decreased during the culture time and was no longer detectable on day 5. At this time, incubation of the cell cultures with PBL conditioned medium induced the reexpression of Ia-antigens. Supernatants from guinea-pig hepatocyte cultures did not have any negative influence on the expression of the Ia-antigen on Kupffer cells in vitro. These data support the hypothesis that liver macrophages have the potential to behave immunologically as accessory cells and might contribute to local immune responses in acute as well as chronic states of liver diseases.

Animals↗
PubMed1986

Impaired cellular immune responses in chronic renal failure: evidence for a T cell defect.

Cellular immune responses in vitro were studied in 24 patients on chronic hemodialysis and 16 healthy volunteers with normal kidney function. Patients on maintenance hemodialysis had lymphopenia with diminished numbers of both T4+ and T8+ T-lymphocytes. The T4/T8 ratios were within the normal range. Peripheral blood lymphocytes (PBL) showed a diminished proliferative response upon stimulation with concanavalin A, phytohemagglutinin and pokeweed mitogen. When cell surface antigens were used for stimulation (mixed lymphocyte culture) uremic lymphocytes also showed a lower proliferation rate. Although without statistical conformation, there was a tendency by uremic PBL to produce less IL-2 as compared to healthy controls. Moreover, in a PWM driven system, peripheral blood lymphocytes from uremics produced significantly less IgG than PBL from normals. These results support the notion that a profound defect in lymphocyte function accounts at least, in part, for the observed immunodeficiency of uremic patients.

Adult↗