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L Stitz

Publications and source records attributed to L Stitz.

At least 55 records · Page 3Linked to original sources
PubMed1992

Preventive effects of early anti-CD4 or anti-CD8 treatment on Borna disease in rats.

Borna disease is a virus-induced, immunopathological encephalomyelitis in which CD4+ cells and macrophages dominate the pathological picture. However, significant numbers of CD8+ cells have been morphologically identified in perivascular infiltrates as well. To determine the contribution of different T-cell subsets to the pathogenesis of Borna disease, virus-infected rats were treated with monoclonal antibodies specific for CD4+ and CD8+ cells. Both types of monoclonal antibodies were able to significantly decrease or even prevent the local inflammatory reaction in the brain if given early during the infection. However, CD8-specific monoclonal antibodies appeared to be more effective than antibodies directed against CD4+ cells. Treatment initiated 4 days postinfection did not result in inhibition of encephalitis and disease. Virus titers in the brain of infected rats treated with T-cell-specific antibodies did not differ from titers in untreated infected control animals. The results indicate an important functional role of CD8+ cells, in addition to CD4+ cells, in the pathogenesis of Borna disease.

Animals↗
PubMed1991

Transforming growth factor-beta modulates T cell-mediated encephalitis caused by Borna disease virus. Pathogenic importance of CD8+ cells and suppression of antibody formation.

Borna disease is a virus-induced, immune-mediated encephalomyelitis based on a delayed-type hypersensitivity reaction. The severity of clinical symptoms after intracerebral infection of rats with Borna disease virus was reduced after treatment with transforming growth factor (TGF-beta 2). Intraperitoneal injection of the recombinant molecule, rTGF-beta 2, started on the day of infection at a dose of either 1 micrograms given every day or every other day for 8 consecutive days or 2 micrograms every third day, was found to result in the absence of typical Borna disease symptoms at 14 days after infection in most of the TGF-beta-treated rats, a time point at which all infected control animals not treated with rTGF-beta 2 showed distinct signs of Borna disease. The inhibition of the disease was paralleled by a significant reduction of the inflammatory reaction in the brain. However, the efficacy of treatment with rTGF-beta 2 was transient, because after day 21 only a slight or no reduction of the inflammatory reaction and, consequently, symptoms of Borna disease could be observed. Immunohistologic investigations revealed reduced CD4+ T cell numbers and no changes in macrophage counts in encephalitic lesions of rTG-beta treated rats. However, CD8+ cells were markedly decreased in the encephalitic lesions. Furthermore, the expression of MHC class II Ag was significantly reduced in the brain of rTGF-beta 2 treated Borna disease virus-infected rats, whereas MHC class I Ag expression was not. Most treated animals showed a reduction of Borna disease virus-specific serum antibodies, the result of an inhibition of the IgG response. The results presented here suggest a distinct influence of rTGF-beta 2 on T cell-mediated immune functions during the early phase of Borna disease virus-induced encephalomyelitis.

Animals↗
PubMed1991

Atypical dissemination of the highly neurotropic Borna disease virus during persistent infection in cyclosporine A-treated, immunosuppressed rats.

In adult rats infected with Borna disease virus, the virus was found exclusively in the brain, whereas in cyclosporine A-treated rats, infectious virus was also detected in peripheral nerve fibers and, unexpectedly, in adjacent organ-specific cells. In contrast to untreated virus-infected rats, no major histocompatibility complex class II expression was found in the brain of cyclosporine A-treated animals.

Animals↗
PubMed1991

[Immune intervention in Borna disease].

Borna disease is a naturally occurring meningoencephalomyelitis of sheep and horses. After experimental infection of rats with Borna disease virus a biphasic disease with initial gait disturbances and later paresis and paralysis can be observed. The disease symptoms in these experimental animals resemble those of the natural hosts. The disease is not caused by the infecting virus itself but rather by a CD4+ T cell-mediated immune response. After the pathogenesis had been elucidated new strategies for the therapy of Borna disease by interfering with the immune reaction have been developed. Treatment with immunosuppressive drugs, with monoclonal antibodies directed against certain immune cells and with mediators of the immune reaction resulted in an inhibition or significant reduction of Borna disease symptoms.

Animals↗
PubMed1991

[Immunopathogenesis of Borna disease].

An overview of the pathogenesis of Borna disease (BD) in rats as a model for the naturally occurring infection in horses and sheep is presented. Our findings revealed a virus infection in which a virus-specific T cell-mediated immune response leads to disease. The immune cells capable of mediating this immunopathological reaction were defined as helper/inducer T cells. In all, the described observations indicate that CD4+ T cells and macrophages trigger a delayed-type hypersensitivity reaction and cause BD together with other cells of the immune system.

Animals↗
PubMed1991

Molecular and immunopathological studies of borna disease virus infection in rats.

Borna disease virus is an agent distinct from all known viruses. Pathogenesis of its infection is also unique. This review highlights several aspects of the biology of this viral infection and the preliminary characterization of the agent. BDV can be used to answer important questions in neurobiology. These include neuroinvasiveness and neurotropism of viral agents, CD4+ T cell-mediated immunopathology and tolerance in newborn animals to a persistent viral infection in the CNS and behavioral diseases and eating disorders induced by neurotropic viruses. This review is dedicated to Prof. Dr. Rott on occasion of his 65th birthday in recognition of his immense contributions to studies on Borna disease and also for his success focusing the attention of the scientific community to this still evolving unique viral disease.

Animals↗
PubMed1991

Persistent virus infections in studies of the immune response.

Some recent studies on immune phenomena in persistent virus infections, employing non-cytolytic viruses, are reviewed. This includes the refutation of a possible inheritance of tolerance and some aspects of drug-induced tolerance to persistent viruses, with its consequences for possible treatment of virus-induced immunopathological diseases. The biological peculiarities of viruses involved in persistent or chronic infections are discussed with respect to the balance between the immune system and the infectious agent.

Animals↗
PubMed1990

Determination of immune cells and expression of major histocompatibility complex class II antigen in encephalitic lesions of experimental Borna disease.

After intracerebral infection with Borna disease virus adult Lewis rats develop a virus-induced immunopathological reaction resulting in severe neurological symptoms and a non-purulent meningoencephalitis. The composition of inflammatory cells and major histocompatibility complex (MHC) class II antigen expression during the course of the infection was investigated using immunocytochemistry with a panel of monoclonal antibodies (mAb). Macrophages and lymphocytes of the T helper phenotype (CD4+) were dominant at all stages of infection, whereas T suppressor/cytotoxic lymphocytes (CD8+) were less frequent. B lymphocytes and plasma cells occurred mainly during later stages of the disease and marked parenchymal deposition of immunoglobulin developed. Beginning 10 days after infection massive expression of MHC class II antigen was noted up to the termination of experiments 70 days after infection. Besides lymphatic cells and macrophages, cells morphologically resembling microglia expressed this antigen. Furthermore, ependymal cells were found positive for MHC class II expression during infection whereas astrocytes remained negative. These findings are consistent with previous results which provide evidence for a delayed-type hypersensitivity reaction being operative in the pathogenesis of Borna disease.

Animals↗
PubMed1990

Immunogenic properties of ISCOM prepared with influenza virus nucleoprotein.

After covalent attachment of bacterial lipopolysaccharide to the nucleoprotein of influenza A virus, this water-soluble antigen could be incorporated firmly into ISCOM. This potent "immunostimulating complex" induced the production of high antibody titers in mice and could partially protect the animals from a lethal challenge infection. After immunization with ISCOM preparations NP-specific cytotoxic T cell activity could not be demonstrated.

Adjuvants, Immunologic↗
PubMed1990

Borna disease virus-induced meningoencephalomyelitis caused by a virus-specific CD4+ T cell-mediated immune reaction.

After intracerebral inoculation of Borna disease virus (BDV). Lewis rats develop a persistent infection of the central nervous system which is pathohistologically represented by perivascular encephalitic lesions predominantly in the grey matter. In previous studies it has been shown that a cell-mediated immune response causes Borna disease (BD). In order to define further the immune cell responsible for this immunopathological disease, a BDV-specific T cell line, NM1, was established and cultured in vitro. Phenotypically this T cell line was characterized by cytofluorometry as CD4-positive (CD4+). Proliferation assays with syngeneic and allogeneic antigen-presenting cells, and blocking experiments with monoclonal antibodies, revealed major histocompatibility complex class II antigens to be restriction elements. After passive transfer of this virus-specific CD4+ T cell into immunosuppressed BDV-infected recipients, full-blown disease could be induced. Immunohistological examination of the cells involved in perivascular inflammatory infiltrates in BDV-infected rats and in recipients of the NM1 T cell line revealed a dominance of macrophages and CD4+ T cells. The presence of these cells in encephalitic lesions strongly suggests a delayed type of hypersensitivity reaction as the pathogenetic mechanism of BD.

Animals↗
PubMed1990

Characterization and immunological properties of influenza A virus nucleoprotein (NP): cell-associated NP isolated from infected cells or viral NP expressed by vaccinia recombinant virus do not confer protection.

A nucleoprotein (NP) preparation purified from the chorioallantoic membrane of chicken eggs infected with fowl plague virus (A/FPV/Rostock/34, H7N1) yielded, in addition to the commonly known 56K protein, a 42K component that could not be detected in virus particles. After testing with a series of NP-specific monoclonal antibodies it was found that some reacted with both proteins and others were bound only by the 56K protein. Among both types of NP-specific monoclonal antibodies only a limited number were bound to infected murine cells. Some antibodies bound to cells infected with a given subtype failed to react with the surface of cells infected with a different subtype. Binding was demonstrated by cellular ELISA, radioimmunoassay and immunofluorescence. The results indicate that only restricted antigenic domains of the native NP and perhaps NP fragments are exposed at the surface of infected murine cells. Additionally, the purified NP preparation was used to immunize mice in order to determine the protective capacity of cell-associated NP. In parallel, and as a relevant control, mice were immunized with a vaccinia virus recombinant containing the gene for NP prior to challenge with infectious virus. High levels of monospecific antibodies and a cytotoxic T cell activity was found in mice immunized with purified NP or infected with the vaccinia recombinant after secondary restimulation in vitro. After treatment with specific antibodies the cytotoxic cells were shown to be classical CD8+ cytotoxic T lymphocytes. Despite the elicitation of a humoral and a cellular immune response by the forms of NP employed mice were not protected from influenza virus infection.

Animals↗
PubMed1989

Inhibition of immune-mediated meningoencephalitis in persistently Borna disease virus-infected rats by cyclosporine A.

In rats persistently infected with Borna disease virus (BDV), severe neurologic disorders and occasional death are the consequences of a T cell-mediated immunopathologic reaction in the brain. It is shown here that the pathologic alterations in the brain and as a result, Borna Disease (BD) can be prevented if animals are treated with the immunosuppressive drug cyclosporine A (CSA) under the following optimal conditions: greater than or equal to 25 mg/kg/day of CSA, started before infection and given for 4 wk. Rats treated with lower doses of CSA, for shorter periods or after infection displayed encephalitic lesions and developed BD. When CSA treatment was begun even as early as 1 day after infection, encephalitis and disease were not influenced. Immune spleen cells passively transferred into CSA-treated rats induced the disease in the recipients, whereas lymphoid cells from CSA-treated rats did not induce BD in infected cyclophosphamide-treated recipients. Antibodies were not involved in BD because rats treated with CSA revealed an inhibition of the synthesis of virus-specific antibodies for all regimens of treatment used (whether successful in preventing BD or not). After i.v. challenge of CSA-treated healthy rats with BDV, antiviral antibodies at low titers could be induced in some animals; however, no encephalitis or disease symptoms could be observed at any time after infection. The same was true for rats reinfected intracerebrally with BDV after discontinuation of CSA. These results support the hypothesis that unresponsiveness and even tolerance can be induced by CSA in the presence of the foreign Ag, demonstrating the beneficial effect of this immunosuppressive drug during a persistent viral infection.

Animals↗
PubMed1988

An easy and rapid method to screen large numbers of antibodies against internal cellular determinants.

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.

Antibodies, Monoclonal↗
PubMed1988

Immune-mediated pathogenesis of Borna disease.

Borna disease is an endemic progressive encephalomyelitis of horses and sheep prevalent in central Europe. A wide variety of animal species, ranging from chickens to primates can be infected experimentally with the causative virus, which is only poorly characterized. Furthermore, BD virus-specific antibodies have been detected in sera and cerebrospinal fluids of psychiatric patients. Our studies on the pathogenesis of BD have shown that-at least in rats-the disease is not caused by the infecting virus itself, but by a virus-induced immunopathological reaction. Thus, after intracerebral infection immunoincompetent rats do not get the disease despite persistent virus replication in cells of the central nervous system. However, after adoptive transfer of immune cells from diseased rats, immunoincompetent rats exhibit full-blown BD. Recently, we have been successful in establishing a virus-specific T cell line of the helper/inducer phenotype (CD4+). This T cell was shown to play an important role in the pathogenesis of BD, suggesting that the disease is caused by a delayed type hypersensitivity reaction.

Animals↗
PubMed1987

Monoclonal antibodies against viral determinants are not restricted to the K/D end of the major histocompatibility complex.

Monoclonal antibodies against lymphocytic choriomeningitis virus (LCMV), a natural, high-replicating, noncytolytic pathogen in mice, were obtained from fusions between myeloma cells and lymphoid cells of mice of different H-2 haplotypes at various times (4-24 d) after infection. Supernatants from growing hybridomas were tested in a RIA, and approximately 15% of all supernatants were positive when tested for specificity on infected vs. uninfected cells of different haplotypes. Upon retesting for specific fluorescence, only some RIA+ supernatants exhibited specific surface staining of acetone-fixed infected cells or unfixed infected cells. In all these experiments and using various detection methods we could not find antibodies with any preference of recognition of viral antigen in conjunction with the H-2 haplotype of the responder mouse. The absence of H-2 restricted antibodies after a primary virus infection in vivo, whether assayed by RIA or surface immunofluorescence, suggests that antibodies obtained in other experiments using infected tumor cells for induction and in the RIA may not represent the general case.

Animals↗
PubMed1987

Neurogenic spread of Semliki Forest virus in mice.

We present evidence that in SFV-infected mice the virus invades the brain via nervous tracts, and that in the early stage of infection of the brain itself dissemination is restricted to neurons. After intranasal (i.n.) application, migration along the neuronal route appeared to be the principle mechanism of spread irrespective of the virulence of the strain used. After subcutaneous (s.c.) infection, neuronal spread could also be demonstrated, however the pattern and time course of brain invasion were different. The LD50 of strain Hd depended significantly on the route of virus application: compared with the i.n. route, its value increased after s.c. infection. This increase was correlated with high plasma interferon induction and natural killer cell activation. In contrast, these activities were virtually absent during the early course after i.n. infection.

Administration, Intranasal↗
PubMed1986

Effect of rabbit anti-asialo GM1 treatment in vivo or with anti-asialo GM1 plus complement in vitro on cytotoxic T cell activities.

The susceptibility of cytotoxic effector lymphocytes and their induction to in vivo or in vitro treatment with rabbit anti-neutral glycolipid ganglio-N-tetraosylceramide (anti-ASGM1) antiserum was investigated. Intravenous injection of anti-ASGM1 antiserum eliminated measurable natural killer (NK) cell activity in spleen cells of mice infected for 5 days with Vaccinia virus, or for 8 days with lymphocytic choriomeningitis virus (LCMV) if injected 24 hr prior to testing. In addition, this treatment lowered measurable virus-specific cytotoxic T cell activity by 60 to 95%. Virus-specific cytotoxic T cell and NK cell activity generated during a primary infection in vivo was also sensitive to treatment in vitro with anti-ASGM1 antiserum (1/300 to 1/600 dilution) plus rabbit complement at a dilution of 1/15 (20 to 50% cell death, more than 30-fold decrease of cytotoxic activity); in vitro treatment with rabbit complement alone often enhanced NK and cytotoxic T cell activity slightly. In vivo treatment with anti-ASGM1 before primary immunization decreased generation of primary CTL only if high doses of anti-ASGM1 antiserum were injected twice. Antiviral T cells generated during secondary stimulation in vitro and alloreactive cytotoxic T cells from a mixed lymphocyte culture were resistant to treatment in vitro with anti-ASGM1 plus complement at the end of the culture period. Treatment in vitro of in vivo-primed responder spleen cells with anti-ASGM1 plus complement before their addition to a secondary restimulation culture resulted in complete inhibition of a secondary antiviral cytotoxic T cell response. In vivo treatment with anti-ASGM1 24 hr before their spleen cells were harvested and restimulated in vitro significantly reduced the virus-specific T cell activity of mice that had been immunized with virus several weeks previously. A cloned T cell line exclusively exerting NK-like activity was resistant, and two cloned virus-specific cytotoxic T cell lines were susceptible to treatment with anti-ASGM1 plus complement in vitro. These results caution the general use of rabbit anti-ASGM1 as a marker to distinguish NK from CTL cells; they indicate a possible relationship between NK and CTL cells and suggest that in vitro culture of lymphocytes may alter or select the cell surface expression or availability of the ASGM1 marker(s).

Animals↗