23 results on '"Hengartner H"'
Search Results
2. Outlook
- Author
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ZINKERNAGEL, R, primary and HENGARTNER, H, additional
- Published
- 1996
- Full Text
- View/download PDF
3. HYBRID I REGION ANTIGENS AND I REGION RESTRICTION OF RECOGNITION IN MLR
- Author
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Fathman, C.G., primary and Hengartner, H., additional
- Published
- 1979
- Full Text
- View/download PDF
4. Temporal trends in incidence of childhood cancer in Switzerland, 1985-2014.
- Author
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Sommer G, Schindler M, Redmond S, Pfeiffer V, Konstantinoudis G, Ammann RA, Ansari M, Hengartner H, Michel G, and Kuehni CE
- Subjects
- Adolescent, Child, Child, Preschool, Female, History, 20th Century, History, 21st Century, Humans, Incidence, Infant, Infant, Newborn, Male, Risk Factors, Switzerland, Cancer Survivors statistics & numerical data
- Abstract
Background: Incidence of childhood cancer increased in most countries worldwide, but reasons are unclear. This study investigates trends of childhood cancer incidence in Switzerland from 1985 to 2014., Methods: We extracted data on all childhood cancer cases diagnosed at ages 0-14 years in Switzerland from the Swiss Childhood Cancer Registry. We included ICCC-3 main groups I-XII and calculated age-standardised, cumulative, and age-specific incidence for different diagnostic groups. We analysed trends of annual age-standardised incidence using JoinPoint regression models., Results: Over the study period from 1985 to 2014, 5104 of 5486 cancer diagnoses (93%) were microscopically verified. The proportion of children treated in paediatric cancer centres increased from 84% during 1985-1994 to 93% in 1995-2004 and 98% in 2005-2014 (p < 0.001). Using the World standard population, age-standardised incidence was 143 in 1985-1994, 154 in 1995-2004, and 162 per million in 2005-2014. Incidence increased by 0.7% (95% confidence interval (CI) 0.5; 1.0) per year for all cancers from 1985 to 2014, 0.8% (95% CI 0.2%-1.4%) for leukaemias over the same period, 3.0% (95% CI 0.2%-1.4%) for CNS tumours during 1985-2002, and 3.8% (95% CI 1.7%-6.0%) for epithelial neoplasms and melanomas over the period 1985-2014., Conclusion: Trends in incidence were driven mostly by increases among leukaemias and CNS tumours. For CNS tumours, observed trends may be explained at least partially by diagnostic changes and improved registration. For leukaemias, rising incidence may be real and due to risk factors that experience similar increases in trends., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
5. Dendritic cells in autoimmune diseases.
- Author
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Ludewig B, Junt T, Hengartner H, and Zinkernagel RM
- Subjects
- Animals, Antigen Presentation, Autoantigens metabolism, Autoimmunity, Humans, Inflammation immunology, Mice, Models, Immunological, T-Lymphocytes immunology, Autoimmune Diseases immunology, Dendritic Cells immunology
- Abstract
Subclinical autoimmune responses can be frequently detected in healthy individuals. Sustained activation of autoreactive lymphocytes is, however, required for the development of autoimmune diseases associated with ongoing tissue destruction either in single organs or generalized with multiple manifestations. Clinical and experimental evidence suggests that prolonged presentation of self antigens by dendritic cells is crucial for the development of destructive autoimmune disease. We discuss here a simplified threshold model where the key parameters for the magnitude of the autoimmune response are the amount of previously ignored self peptides presented by dendritic cells and the duration of the antigen presentation in secondary lymphoid organs. Multiple factors influence the threshold for the conversion of an autoimmune response to overt autoimmune disease. Frequent or persistent viral infections of the target organ may favor autoimmune disease by increasing the amounts of released self antigens, generating cytokine-mediated bystander activation of self-reactive lymphocytes and/or sustaining a chronic response via neoformation of lymphoid structures in the target organ.
- Published
- 2001
- Full Text
- View/download PDF
6. Mathematical model of a virus-neutralizing immunglobulin response.
- Author
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Funk GA, Barbour AD, Hengartner H, and Kalinke U
- Subjects
- Animals, Antibodies, Viral blood, B-Lymphocytes immunology, Immunoglobulin G immunology, Immunoglobulin M immunology, Lymphocyte Activation, Mice, T-Lymphocytes immunology, Time Factors, Immunoglobulins immunology, Models, Immunological, Rhabdoviridae Infections immunology, Spleen immunology, Vesicular stomatitis Indiana virus
- Abstract
We present a mathematical model to simulate the kinetics of B-cell activation and the virus-neutralizing immunoglobulin response in the spleen of mice after infection with vesicular stomatitis virus (VSV). Our model combines data from in vitro experiments and in vivo kinetic observations. A system of eight nonlinear differential equations was used in the computer experiments and numerically solved. The isotype switch from IgM to IgG in the presence of T-cell help was modelled by a time variable function, used as a parameter. The model solutions indicate fast kinetics of the generation of VSV-neutralizing IgM antibodies within 2-3 days post immunization peaking on day 5 at a serum concentration of approximately 80 microgram ml-1 IgM, which is the equivalent to about 10% of the total IgM serum concentration. The frequency of virus-specific B cells increases about 1000-fold within the first 4 days after immunization. Protective levels of VSV-neutralizing IgG antibodies (>/=10 microgram ml-1) are reached within 5 to 6 days post immunization. Fitting the model solution to the experimentally observed neutralizing serum titers suggests an increase in the neutralizing activity of IgGs occurring between days 5 and 8 post-infection. The model indicates that less than 10 VSV-specific B cells have to be triggered daily to maintain protective IgG serum titers during the memory phase., (Copyright 1998 Academic Press.)
- Published
- 1998
- Full Text
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7. A comparison of efficacy and specificity of three NK depleting antibodies.
- Author
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Ehl S, Nuesch R, Tanaka T, Myasaka M, Hengartner H, and Zinkernagel R
- Subjects
- Animals, Antigens immunology, Antigens, Ly, Antigens, Surface, Cytotoxicity, Immunologic, G(M1) Ganglioside immunology, Immunity, Cellular, Lectins, C-Type, Lymphocytic choriomeningitis virus immunology, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, NK Cell Lectin-Like Receptor Subfamily B, Proteins immunology, Receptors, Interleukin-2 immunology, T-Lymphocytes, Cytotoxic immunology, Killer Cells, Natural immunology, Lymphocyte Depletion methods
- Abstract
This study compares in vivo efficacy and specificity of the three NK cell depleting antibodies anti-asialo GM1, anti-NK 1.1 and the recently described TM beta 1, which is directed against the interleukin-2 receptor beta chain. All three antibodies are equally efficacious as assessed by abolishing NK mediated cytolytic activity induced by a high dose virus infection or Poly IC against YAC-1 targets. Similarly, the generation of virus-specific cytotoxic T cells (CTL) was unimpaired after NK depletion in two different virus infections. However, if mice are treated with the antibodies several days after virus infection, when strong CTL responses have already been generated, anti-asialo GM1 and-to a lesser extent-also TM beta 1 have a significant effect on CTL activity. Only after treatment with anti-NK 1.1 antibody, CTL activity was not significantly impaired. We conclude, that of the NK depleting antibodies currently available, anti-NK 1.1 allows the best differentiation of activated CTL and NK cells in vivo.
- Published
- 1996
- Full Text
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8. Different roles for cytotoxic T cells in the control of infections with cytopathic versus noncytopathic viruses.
- Author
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Kägi D and Hengartner H
- Subjects
- Animals, Cytopathogenic Effect, Viral, T-Lymphocytes, Cytotoxic immunology, Virus Diseases immunology, Viruses immunology, Viruses pathogenicity
- Abstract
The assessment of the role of T-cell-mediated cytotoxicity in immunity to viral infections has been difficult to address directly and therefore has been controversial. Recent experiments with perforin-deficient mice have shown that cytotoxicity is crucial for the resolution of infection with lymphocytic choriomeningitis virus but not for the resolution of infection with vaccinia, vesicular stomatitis, Semliki Forest or influenza virus. These findings may reflect the general pattern that T-cell-mediated cytotoxicity is crucial only for the resolution of infections with noncytopathic viruses, whereas infections with cytopathic viruses are mainly controlled by soluble mediators such as antibodies and interferons.
- Published
- 1996
- Full Text
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9. T-independent activation of B cells by vesicular stomatitis virus: no evidence for the need of a second signal.
- Author
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Fehr T, Bachmann MF, Bluethmann H, Kikutani H, Hengartner H, and Zinkernagel RM
- Subjects
- Animals, Antibodies, Viral biosynthesis, Antigens, Viral immunology, B-Lymphocytes virology, CD40 Antigens genetics, CD40 Antigens physiology, Complement C3 antagonists & inhibitors, Complement C3 immunology, Elapid Venoms pharmacology, Immunization, Immunoglobulin M biosynthesis, Killer Cells, Natural immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Nucleopolyhedroviruses genetics, Receptors, Tumor Necrosis Factor deficiency, Receptors, Tumor Necrosis Factor genetics, Receptors, Tumor Necrosis Factor physiology, Recombinant Fusion Proteins immunology, T-Lymphocytes, Helper-Inducer immunology, Viral Envelope Proteins immunology, Viral Vaccines immunology, B-Lymphocytes immunology, Lymphocyte Activation, Membrane Glycoproteins, Signal Transduction physiology, Vesicular stomatitis Indiana virus physiology
- Abstract
Vesicular stomatitis virus (VSV) induces a T helper cell-independent IgM antibody response, whereas the IgG response is strictly T helper cell dependent. Since VSV induces B cells in complete absence of T helper cells, the question arises as to whether this induction occurs in the absence of a second signal or whether it depends upon an alternative or replacing signal 2. We therefore asked whether VSV has polyclonal B cell stimulator activity and/or whether B cell induction by VSV needs costimulation via complement or tumor necrosis factor (TNF) receptor or by natural killer (NK) cell activity. In vitro B cell proliferation assays and analysis of the in vivo antibody response in CD40-deficient mice excluded that VSV has properties of a polyclonal B cell stimulator. C3 depletion by cobra venom factor and application of anti-complement receptor antibodies showed that the T-independent IgM response was largely C3-independent except under very limiting antigen doses. Immunization of TNF receptor-deficient mice showed a normal anti-VSV IgM response, and in a cytotoxicity assay on YAC target cells there was no evidence of NK cell activation by VSV. Thus, VSV seems to induce B cells without polyclonal activation and/or C3, TNF, or NK cells functioning as a replacing second signal.
- Published
- 1996
- Full Text
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10. Mapping of the dominant neutralizing antigenic site of a virus using infected cells.
- Author
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Roost HP, Haag A, Burkhart C, Zinkernagel RM, and Hengartner H
- Subjects
- Animals, Antibodies, Monoclonal immunology, Antigen-Antibody Reactions, Antigens, Surface analysis, Chlorocebus aethiops, Epitope Mapping, Mice, Mice, Inbred BALB C, Rats, Rats, Inbred Lew, Vero Cells, Antigens, Viral analysis, Vesicular stomatitis Indiana virus immunology
- Abstract
Panels of neutralizing monoclonal antibodies (MAbs) and antisera to vesicular stomatitis virus of the serotype Indiana (VSV-IND) were generated in mice and rats. They were used in competition studies to map epitopes on the viral glycoprotein that are involved in virus neutralization. Since neutralizing antibodies bind to the viral glycoproteins on the surface of intact viruses and of infected cells, infected cells were used for measuring the binding of competing antibodies by cytofluorometric analysis. A single immunodominant neutralizing epitope was recognised by 90% (58) of the MAbs including all of strong neutralizing capacity. 10% (6) of the neutralizing MAbs that all exhibited low neutralizing titers recognised spatially closely related epitopes. This approach offers a convenient method to determine antibody interaction with complex conformational epitopes of membrane proteins.
- Published
- 1996
- Full Text
- View/download PDF
11. Antiviral immune responses of mice lacking MHC class II or its associated invariant chain.
- Author
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Battegay M, Bachmann MF, Burhkart C, Viville S, Benoist C, Mathis D, Hengartner H, and Zinkernagel RM
- Subjects
- Animals, Antigen-Presenting Cells physiology, Capsid immunology, Mice, Mice, Inbred C57BL, T-Lymphocytes, Cytotoxic immunology, Viral Core Proteins immunology, Viral Envelope Proteins immunology, Antibodies, Viral biosynthesis, Antigens, Differentiation, B-Lymphocyte physiology, Histocompatibility Antigens Class II physiology, Membrane Glycoproteins
- Abstract
Induction of T-helper cells and T-B cell interaction have been considered to critically depend upon recognition of major histocompatibility complex (MHC) class II molecules by the T cell receptor. Mice lacking either MHC class II molecules (class II(0/0) mice) or its associated invariant chain (Ii0/0 mice) provide new opportunities to test this premise. Immune responses to some protein antigens have been studied in these mice; little is known about their ability to withstand viral infections. We therefore tested CD8+ effector T cells and CD4+ T-cell-dependent B cell function during different viral infections. The vesicular stomatitis virus (VSV)-specific primary cytotoxic T cell response which is largely T-helper-dependent was diminished in Ii(0/0) and absent in class II(0/0) mice. The usually less T-helper-dependent cytotoxic vaccinia or lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cell responses were reduced up to ninefold in class II(0/0) and up to threefold in Ii(0/0) mice. In class II(0/0) mice, the T-helper-independent neutralizing IgM response against the glycoprotein of VSV was within normal ranges but, in contrast to previous results on CD4(0/0) mice, the T-helper-dependent IgG response was absent. Ii(0/0) mice exhibited a normal neutralizing IgM response; in contrast to class II(0/0) mice, they mounted a significant, though reduced specific IgG response. Similar results were obtained for antibody responses against the nucleoprotein of VSV. Although the T-helper-cell response upon infection with VSV seemed diminished only a little in Ii(0/0) mice, presentation of VSV-G to a class II-restricted specific hybridoma was greater than 300-fold reduced in the absence of Ii. This suggests that local protein concentrations reached during viral infection in the host are high enough to override the Ii deficiency of antigen-presenting cells in vivo.
- Published
- 1996
- Full Text
- View/download PDF
12. Escape of thymocytes and mature T cells from clonal deletion due to limiting tolerogen expression levels.
- Author
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Oehen SU, Ohashi PS, Bürki K, Hengartner H, Zinkernagel RM, and Aichele P
- Subjects
- Animals, Bone Marrow Transplantation, Cytotoxicity Tests, Immunologic, Flow Cytometry, Glycoproteins biosynthesis, Glycoproteins immunology, Lymphocyte Activation, Lymphocytic choriomeningitis virus immunology, Major Histocompatibility Complex genetics, Mice, Mice, Transgenic, Radiation Chimera immunology, Transcription, Genetic, Viral Proteins biosynthesis, Viral Proteins immunology, Clonal Deletion physiology, Immune Tolerance immunology, Self Tolerance immunology, T-Lymphocytes, Cytotoxic immunology, Thymus Gland cytology
- Abstract
Expression of self antigen on lymphohemopoietic cells and in the thymus has been shown to cause tolerance by negative selection. To investigate the role of self antigen expression levels on the induction of tolerance, we generated transgenic mice expressing the lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) driven by the H-2Kb promoter. Two mouse lines differing in transgene expression levels were obtained and evaluated for the induction of tolerance to LCMV-GP. LCMV-GP high (GPhi) expressing animals thymically deleted self-reactive thymocytes. Low expressors (GPlo) partially deleted self-reactive mature T cells in the periphery in the absence of any obvious signs of negative selection in the thymus. Functionally, the LCMV-GP-specific cytotoxic T cell (CTL) response was absent in GPhi mice, whereas GPlo mice produced diminished LCMV-GP-specific CTL responses. Therefore limiting levels of expression of self antigen influence efficiency of negative selection, enabling potentially self-reactive T cells to escape from tolerance induction.
- Published
- 1994
- Full Text
- View/download PDF
13. Comparison of the sensitivity of in vivo and in vitro assays for detection of antiviral cytotoxic T cell activity.
- Author
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Castelmur I, DiPaolo C, Bachmann MF, Hengartner H, Zinkernagel RM, and Kündig TM
- Subjects
- Animals, Edema immunology, Edema microbiology, Female, In Vitro Techniques, Lymphocytic Choriomeningitis immunology, Meninges microbiology, Mice, Mice, Inbred C57BL, Ovary microbiology, Sensitivity and Specificity, Spleen cytology, Spleen microbiology, Virus Replication immunology, Cytotoxicity Tests, Immunologic methods, Immunologic Memory physiology, Lymphocytic choriomeningitis virus immunology, T-Lymphocytes, Cytotoxic immunology
- Abstract
Sensitivities of in vitro and in vivo assays for the detection of lymphocytic choriomeningitis virus (LCMV)-specific CTL were compared. Measurement of primary cytotoxicity was the least sensitive of all the tested assays. However, when the same 51Cr release assays were performed after in vitro restimulation, this in vitro method was found to be more sensitive than all of the five in vivo assays tested. Assessment of CTL-mediated protection against LCMV replication in spleens was most sensitive among the in vivo tests, followed by CTL-mediated resistance to intracerebral or intraperitoneal challenge infections with vaccinia-LCMV-recombinant virus. Inhibition of LCMV-induced choriomeningitis and of the footpad swelling reaction were least sensitive in detecting LCMV-specific CTL. As discussed, the presented sensitivity gradient may most probably be generalized.
- Published
- 1993
- Full Text
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14. Virally induced immunosuppression.
- Author
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Zinkernagel RM and Hengartner H
- Subjects
- Acquired Immunodeficiency Syndrome immunology, Animals, Antibodies, Viral immunology, Antigen-Presenting Cells immunology, HIV growth & development, HIV immunology, Humans, Macrophages microbiology, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Regulatory immunology, Immune Tolerance, Lymphocytic choriomeningitis virus immunology
- Abstract
A mouse model of virus-triggered, T-cell mediated acquired immunosuppression is analyzed. Lymphocytic choriomeningitis virus initially infects mostly macrophages and antigen-presenting cells; these are destroyed by lymphocytic choriomeningitis virus specific cytotoxic T cells resulting in immunosuppression. Similar immunopathological mechanisms may play a role in acquired immune deficiency syndrome.
- Published
- 1992
- Full Text
- View/download PDF
15. T cells causing immunological disease: immunopathology or autoimmunity?
- Author
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Zinkernagel RM and Hengartner H
- Subjects
- Animals, Antigen-Presenting Cells immunology, Autoantigens, Autoimmunity, Immune Tolerance, Mice, T-Lymphocytes pathology, Immune System Diseases etiology, T-Lymphocytes immunology
- Published
- 1992
- Full Text
- View/download PDF
16. Recombinant vaccines.
- Author
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Oehen S, Hengartner H, and Zinkernagel R
- Subjects
- Humans, Vaccines, Synthetic immunology, Viral Vaccines immunology, Vaccination adverse effects, Vaccines, Synthetic adverse effects, Viral Vaccines adverse effects
- Published
- 1991
- Full Text
- View/download PDF
17. Immunosuppression in mice by lymphocytic choriomeningitis virus infection: time dependence during primary and absence of effects on secondary antibody responses.
- Author
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Rüedi E, Hengartner H, and Zinkernagel RM
- Subjects
- Animals, Antibodies, Viral biosynthesis, Female, Immunoglobulin G biosynthesis, Immunoglobulin M biosynthesis, Immunologic Memory immunology, Kinetics, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Vesicular stomatitis Indiana virus immunology, Immune Tolerance, Lymphocytic Choriomeningitis immunology
- Abstract
The kinetic study of immunosuppression caused by infection of mice with lymphocytic choriomeningitis virus WE (LCMV-WE) was assessed in DBA/2 (H-2d) and C57BL/6 (H-2b) mice. Infection with LCMV caused suppression of the Day 4 IgM response (complete in DBA/2 and incomplete in C57BL/6) and completely suppressed IgG responses on Days 9 and 42 to vesicular stomatitis virus (VSV) injected 2-11 days after LCMV. Suppression was partial when VSV was injected 16-28 days after LCMV-WE infection. The observed suppression between Day 2 and Day 11 was complete and nonspecific as revealed by the fact that these mice could not mount a secondary response to VSV when reinjected with the same VSV 42 days later. Nonspecificity of suppression was further indicated by the finding that the kinetics of recovery from suppression of the anti-VSV response were comparable for the VSV serotype used during the 2- to 11-day period after LCMV infection as for the serologically noncross-reactive second VSV serotype; both anti-VSV responses had recovered by Days 56-82 after LCMV infection. Once an anti-VSV antibody response was established, a subsequent LCMV-WE infection had no suppressive effect on Day 2 or Day 42 after a primary VSV infection. Also, the capacity of VSV-primed mice that were LCMV infected to respond to VSV in a secondary challenge infection with the same VSV was not impaired.
- Published
- 1990
- Full Text
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18. An easy and rapid method to screen large numbers of antibodies against internal cellular determinants.
- Author
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Stitz L, Hengartner H, Althage A, and Zinkernagel RM
- Subjects
- Antigens, Viral analysis, Cells, Cultured, Antibodies, Monoclonal immunology, Antibodies, Viral analysis, Cytoplasm immunology, Immunologic Techniques, Microscopy, Fluorescence methods
- Abstract
A rapid and easy method is described to screen great numbers of antisera or antibodies against internal cellular antigens including viral antigens or to screen various target cells for proper expression of antigens; the method can also be applied to determine fluorescent foci to enumerate non-cytopathic viruses. Cells, infected with a particular virus or uninfected, adhering to flat-bottomed 96-well microtiter plates were fixed with conventional phosphate-buffered saline containing 4% formaldehyde for 10 min, alternatively, cells were first fixed with 3% paraformaldehyde for 10 min and were then treated with Trition X-100 for another 10 min. After two washes, either fluorescein-labelled antiviral antibodies or first antiviral antibodies followed by labelled anti-species antibodies were applied, incubated and washed off as usual. A few drops of a balanced salt solution were kept in the well and were drained off gently just before the plates were examined. The plates were viewed directly in an inverted UV microscope or were inspected and photographed bottoms up with a conventional UV microscope mounted with an old-fashioned uncorrected objective (20 X) which, because of its shorter length, permitted proper focussing. For most cases studied, sensitivity was comparable to the fluorescence analysis method of cells on slides. The plates could be stored for several months in a dark refrigerator if kept moist. The method is rapid because it avoids individual handling of samples for the washing procedures and does not need growing and mounting of cells on slides; up to 1000 samples can be tested by one person in a day.
- Published
- 1988
- Full Text
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19. Suppression by cyclosporin A of murine T-cell-mediated immunity against viruses in vivo and in vitro.
- Author
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Huegin AW, Cerny A, Hengartner H, and Zinkernagel RM
- Subjects
- Animals, Hypersensitivity, Delayed immunology, Immunologic Memory drug effects, Lymphocyte Activation drug effects, Lymphocytic choriomeningitis virus immunology, Mice, T-Lymphocytes, Cytotoxic drug effects, Vaccinia virus immunology, Vesicular stomatitis Indiana virus immunology, Cyclosporins pharmacology, Cytotoxicity, Immunologic drug effects, Immunosuppressive Agents pharmacology
- Abstract
The immunosuppressive effect of Cyclosporin A on T-cell-mediated antiviral immune responses was examined. When administered intraperitoneally CS-A abrogated anti-vaccinia virus, anti-lymphocytic choriomeningitis virus (LCMV), and anti-vesicular stomatitis virus (VSV) T-cell responses in a dose-dependent fashion. Usually 50-60 mg/kg were efficient in suppressing primary T-cell responses completely. In contrast, 10-20 mg/kg often enhanced T-cell responses significantly when compared with controls. Suppression was observed if CS-A treatment was started before virus injection and up to 12 hr after infection; CS-A given 24 hr after the virus still suppressed T-cell activity partially. A 50 mg/kg dose of CS-A suppressed secondary anti-vaccinia virus or anti-VSV T-cell responses in vivo by a factor of about 10. This dose suppressed the primary T-cell-dependent footpad swelling induced by local LCMV infection and prevented T-cell-mediated immunopathological death due to LCM when LCMV was injected intracerebrally. In addition, clearance of LCMV was delayed drastically by CS-A treatment. When added to cultures of in vivo-primed antiviral T cells that were restimulated in vitro, CS-A inhibited both proliferation as well as generation of virus-specific cytotoxic T cells in a dose-dependent way. The results show that in CS-A-treated mice primary and secondary antiviral T-cell responses are strongly inhibited; acute viral infections with cytopathic viruses may therefore be more dramatic. In contrast immunopathological T-cell-mediated disease caused by noncytopathic viruses such as LCMV may be prevented or attenuated.
- Published
- 1985
- Full Text
- View/download PDF
20. Chromatography of functionalized liposomes and their components.
- Author
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Schott H, Leitner B, Schwendener RA, and Hengartner H
- Subjects
- Avidin analysis, Biotin analysis, Cell Line, Cytarabine therapeutic use, Humans, Immunoglobulin G analysis, Liposomes administration & dosage, Prodrugs analysis, Radioimmunoassay, Cytarabine analysis, Liposomes analysis
- Abstract
The antitumour drug 1-beta-D-arabinofuranosylcytosine (ara C) was acylated by means of oleic acid anhydride, resulting in the prodrug N4-oleoyl-ara C. Together with a lipophilic biotin derivative, this lipophilic prodrug was incorporated into the bilayer membrane of unilamellar liposomes prepared by means of the detergent dialysis method. On addition of these biotinylated prodrug-liposomes to an excess of avidin, biotin residues were complexed with avidin. The unreacted avidin was removed by chromatography on the Ultrogel AcA-22 column. The prodrug-liposome-avidin complex was coupled to biotinylated monoclonal antibodies through the free binding sites of the immobilized avidin. Unreacted antibodies were removed by chromatography on an Ultrogel AcA-22 column. In vitro, the liposome-antibody complexes selectively bound to cells which were recognized by the monoclonal antibodies linked to the liposomes. For this reason, a promising strategy towards a specific chemotherapy of cancer is expected.
- Published
- 1988
- Full Text
- View/download PDF
21. Antiviral T cell competence and restriction specificity of mixed allogeneic (P1 + P2----P1) irradiation chimeras.
- Author
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Rüedi E, Sykes M, Ildstad ST, Chester CH, Althage A, Hengartner H, Sachs DH, and Zinkernagel RM
- Subjects
- Animals, Bone Marrow radiation effects, Cytotoxicity, Immunologic, Epitopes, H-2 Antigens immunology, Immunization, Lymphocytic choriomeningitis virus immunology, Mice, Vaccinia virus immunology, Vesicular stomatitis Indiana virus immunology, Bone Marrow Cells, Immunocompetence, Radiation Chimera, T-Lymphocytes immunology
- Abstract
Mixed irradiation bone marrow chimeras were prepared by reconstituting lethally irradiated C57BL/10 (B10) or B10.D2 mice with T cell-depleted bone marrow cells of B10 plus B10.D2 origin. These chimeras were healthy and survived well under conventional housing conditions and after experimental laboratory infections. Of a total of 17 chimeras tested, 2 died spontaneously or from the injected virus. Twelve of fifteen chimeras mounted a measurable cytotoxic T cell response to virus. Despite approximately equal percentages of B10 and B10.D2 lymphocytes in chimeras, cytotoxic T cell responses to vaccinia virus and lymphocytic choriomeningitis virus were mediated variably by either syngeneic or allogeneic donor lymphocytes; thus the H-2 type of effector T cells frequently did not correspond to the 50:50 distribution of spleen or peripheral blood lymphocytes. Cytotoxic responses were restricted exclusively to recipient H-2 type. All mixed chimeras examined were able to mount a good IgG response to vesicular stomatitis virus. These results confirm previous data suggesting that such mixed chimeras are healthy and immunocompetent and demonstrate strict recipient-determined restriction specificity of effector T cells; they also suggest that if T help is necessary for induction of virus-specific cytotoxic T cells, it does not require host-restricted interactions between helper T cells and precursor cytotoxic T cells.
- Published
- 1989
- Full Text
- View/download PDF
22. 5'-O-Palmitoyl- and 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine--novel lipophilic analogues of 5'-fluoro-2'-deoxyuridine: synthesis, incorporation into liposomes and preliminary biological results.
- Author
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Schwendener RA, Supersaxo A, Rubas W, Weder HG, Hartmann HR, Schott H, Ziegler A, and Hengartner H
- Subjects
- Animals, Antineoplastic Agents administration & dosage, Bone Marrow Diseases chemically induced, Chemical Phenomena, Chemistry, Colonic Neoplasms drug therapy, Female, Floxuridine administration & dosage, Floxuridine chemical synthesis, Floxuridine pharmacology, Mice, Solubility, Antineoplastic Agents chemical synthesis, Floxuridine analogs & derivatives, Liposomes administration & dosage
- Abstract
5'-O-palmitoyl- and 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine were prepared by the reaction of 5-fluoro-2'-deoxyuridine in dimethylacetamide with palmitic acid chloride. The incorporation of the synthesized prodrugs into liposomes composed of egg phosphatidylcholine/stearylamine/cholesterol/alpha-tocopherol at a molar ratio of 10:1:2:0.05 was nearly quantitative; homogeneous bilayer vesicles (75 nm diameter) were obtained. Preliminary tolerance studies revealed that the prodrug-liposome preparations are about 20-60 times more toxic than the parent drug. The prodrugs incorporated into liposomes were 10 to 30 times more active against murine colon 38 carcinoma compared to the free drug. In comparison to the administration of the prodrugs in peanut oil the liposomal preparations seem to exert improved effects and represent a valuable drug delivery system for parenteral applications.
- Published
- 1985
- Full Text
- View/download PDF
23. Primary sequence homology between the effector molecules that mediate complement and T-lymphocyte cytotoxicity.
- Author
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Lowrey DM, Rupp F, Aebischer T, Grey P, Hengartner H, and Podack ER
- Subjects
- Amino Acid Sequence, Animals, Cross Reactions, Mice, Perforin, Pore Forming Cytotoxic Proteins, Sequence Homology, Nucleic Acid, Complement C9 genetics, Membrane Glycoproteins, Membrane Proteins genetics, T-Lymphocytes, Cytotoxic physiology
- Published
- 1987
- Full Text
- View/download PDF
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