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Article: Evidence for MHC I-restricted CD8+ T-cell-mediated immunopathology in canine masticatory muscle myositis and polymyositis.

Neumann, J / Bilzer, T

2006 Volume 33, Issue 2, Page(s) 215–224

Abstract: ... location of CD4(+) and CD8(+)T cells, B cells, macrophages, major histocompatibility complex (MHC) class ... I and class II antigens, and autoantibodies. CD8(+)T cells were found in MMM (91%) and PM (75%), mostly ... paralleled (68% and 61%) by enhanced expression of MHC class I antigen on muscle fibers. CD8(+)T ...

Abstract	Masticatory muscle myositis (MMM) is the most common inflammatory myopathy (IM) in dogs, associated with antibodies against myosin. To further elucidate the immunopathogenesis, we investigated muscles of 53 dogs with MMM, 32 dogs with polymyositis (PM), and 4 dogs suffering from both, with regard to the presence and location of CD4(+) and CD8(+)T cells, B cells, macrophages, major histocompatibility complex (MHC) class I and class II antigens, and autoantibodies. CD8(+)T cells were found in MMM (91%) and PM (75%), mostly paralleled (68% and 61%) by enhanced expression of MHC class I antigen on muscle fibers. CD8(+)T cells invading intact and neighboring necrotic muscle fibers were present in MMM (39%) and PM (42%). Dogs with MMM lacking intramuscular (26%) and circulating (36%) autoantibodies also had CD8(+) T-cell infiltrations and muscle-fiber lesions. Since MHC class I antigen and CD8(+) T cells were detected in the presence of CD4(+) T cells, regardless of antimuscular antibodies, we consider MMM and PM in the dog as a CD8(+) T-cell-mediated immunopathological disease that initiates muscle-fiber destruction and leads to production of myosin autoantibodies.
MeSH term(s)	Animals ; Autoantibodies/immunology ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/pathology ; CD4-Positive T-Lymphocytes/physiology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; Dog Diseases/immunology ; Dog Diseases/physiopathology ; Dogs ; Female ; Genes, MHC Class I ; Genes, MHC Class II ; Immunoglobulin G/analysis ; Immunohistochemistry ; Immunophenotyping ; Macrophages/immunology ; Macrophages/pathology ; Major Histocompatibility Complex/genetics ; Major Histocompatibility Complex/immunology ; Major Histocompatibility Complex/physiology ; Male ; Masticatory Muscles/immunology ; Masticatory Muscles/physiopathology ; Muscle Fibers, Skeletal/immunology ; Muscle Fibers, Skeletal/pathology ; Myosins/immunology ; Myositis/immunology ; Myositis/physiopathology ; Myositis/veterinary ; Polymyositis/immunology ; Polymyositis/physiopathology ; Polymyositis/veterinary
Chemical Substances	Autoantibodies ; Immunoglobulin G ; Myosins (EC 3.6.4.1)
Language	English
Publishing date	2006-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	438353-9
ISSN	1097-4598 ; 0148-639X
ISSN (online)	1097-4598
ISSN	0148-639X
DOI	10.1002/mus.20456
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Zs.A 1449: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Virus-specific CD4+ T cells eliminate borna disease virus from the brain via induction of cytotoxic CD8+ T cells.

Nöske, K / Bilzer, T / Planz, O / Stitz, L

Journal of virology

1998 Volume 72, Issue 5, Page(s) 4387–4395

Abstract: ... with a virus-specific CD4+ T-cell line prior to infection. In rats receiving this treatment, only a transient ... hybridization for both genomic and mRNA, and by immunohistology. Most importantly, in vitro assays revealed that the T-cell line ... by the appearance of CD8+ T cells and the expression of perforin in the brain. Testing of lymphocytes isolated ...

Abstract	Persistent Borna disease virus infection of the brain can be prevented by treatment of naive rats with a virus-specific CD4+ T-cell line prior to infection. In rats receiving this treatment, only a transient low-level encephalitis was seen compared to an increasingly inflammatory reaction in untreated infected control rats. Virus replication was found in the brain for several days after infection before the virus was cleared from the central nervous system. The loss of infectivity from the brain was confirmed by negative results by reverse transcription-PCR with primers for mRNA, by in situ hybridization for both genomic and mRNA, and by immunohistology. Most importantly, in vitro assays revealed that the T-cell line used for transfusion had no cytotoxic capacity. The kinetics of virus clearance were paralleled by the appearance of CD8+ T cells and the expression of perforin in the brain. Testing of lymphocytes isolated from the brains of CD4+ T-cell-treated rats after challenge revealed high cytotoxic activity due to the presence of CD8+ cytotoxic T cells at time points when brain lymphocytes from infected control rats induced low-level cytolysis of target cells. Neutralizing antiviral antibodies and gamma interferon were shown not to be involved in the elimination of virus from the brain.
MeSH term(s)	Animals ; Antibodies, Viral/immunology ; Borna Disease/immunology ; Borna Disease/virology ; Borna disease virus/immunology ; Brain/immunology ; Brain/virology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/virology ; Cell Line ; Cell Transplantation ; Female ; Membrane Glycoproteins/metabolism ; Neutralization Tests ; Perforin ; Pore Forming Cytotoxic Proteins ; Rats ; Rats, Inbred Lew ; T-Lymphocytes, Cytotoxic/immunology ; Vaccination
Chemical Substances	Antibodies, Viral ; Membrane Glycoproteins ; Pore Forming Cytotoxic Proteins ; Perforin (126465-35-8)
Language	English
Publishing date	1998-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.72.5.4387-4395.1998
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Article: Precursors of Borna disease virus-specific T cells in secondary lymphatic tissue of experimentally infected rats.

Batra, Arvind / Planz, Oliver / Bilzer, Thomas / Stitz, Lothar

Journal of neurovirology

2003 Volume 9, Issue 3, Page(s) 325–335

Abstract: ... of T cells in central nervous system disease. Adoptive transfer experiments were performed to investigate ... homing properties of T cells that infiltrate the brains of infected animals. Lymphocytes isolated ... on the presence of transferred lymphocytes. Furthermore, the presence of virus-specific cytotoxic T cells was ...

Abstract	Borna disease in rats represents an experimental model to study the immunopathological role of T cells in central nervous system disease. Adoptive transfer experiments were performed to investigate homing properties of T cells that infiltrate the brains of infected animals. Lymphocytes isolated from the brains of diseased rats were labelled with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) and transferred into immunosuppressed infected recipients. In recipient rats displaying neurological disease, labeled lymphocytes were demonstrated in the vicinity of brain cell lesions, suggesting that the neuronal destruction was dependent on the presence of transferred lymphocytes. Furthermore, the presence of virus-specific cytotoxic T cells was scrutinized in secondary lymphatic tissue and the functional activity of lymphocytes isolated from spleens, cervical lymph nodes, and mesenteric lymph nodes of infected animals was tested immediately after isolation and after in vitro restimulation. The data presented here indicate that precursors of Borna disease virus (BDV)-specific CD8(+) T cells are present and cytotoxic activity was demonstrated after in vitro cocultivation with infected cells in cervical lymph nodes and spleens but not in mesenteric lymphoid tissue. Adoptive transfer of in vitro restimulated T cells induced alterations in BDV-infected, immunosuppressed rats that resemble the well-defined clinical symptoms and neuropathology of Borna disease. This report provides for the first time formal evidence that virus-specific cytotoxic T cells are primed in the periphery after BDV infection, a disease that exclusively manifests itself in the central nervous system.
MeSH term(s)	Adoptive Transfer ; Animals ; Borna Disease/immunology ; Borna Disease/pathology ; Borna disease virus/immunology ; Brain/immunology ; Brain/pathology ; CD8-Positive T-Lymphocytes/immunology ; Chemotaxis, Leukocyte ; Lymph Nodes/immunology ; Lymph Nodes/pathology ; Lymphoid Tissue/immunology ; Lymphoid Tissue/pathology ; Mesentery ; Neck ; Organ Specificity ; Rats ; Rats, Inbred Lew ; Spleen/immunology ; Spleen/pathology ; T-Lymphocyte Subsets/immunology ; T-Lymphocytes, Cytotoxic/immunology
Language	English
Publishing date	2003-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1283265-0
ISSN	1538-2443 ; 1355-0284
ISSN (online)	1538-2443
ISSN	1355-0284
DOI	10.1080/13550280390201038
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Article: High-dose Borna disease virus infection induces a nucleoprotein-specific cytotoxic T-lymphocyte response and prevention of immunopathology.

Furrer, E / Bilzer, T / Stitz, L / Planz, O

Journal of virology

2001 Volume 75, Issue 23, Page(s) 11700–11708

Abstract: ... The virus replicates slowly, and the cellular immune response results in immunopathology. CD8(+) T cells exert effector ... CD8(+) T cells could be demonstrated in the brain. We present evidence that in a noncytolytic and ... in particular the cytotoxic T-cell response, determines whether the virus is controlled with prevention ...

Abstract	Experimental Borna disease virus (BDV) infection of rats and natural infection of horses and sheep leads to severe central nervous system disease based on immunopathological pathways. The virus replicates slowly, and the cellular immune response results in immunopathology. CD8(+) T cells exert effector cell functions, and their activity results in the destruction of virus-infected cells. Previously, Oldach and colleagues (D. Oldach, M. C. Zink, J. M. Pyper, S. Herzog, R. Rott, O. Narayan, and J. E. Clements, Virology 206:426-434, 1995) have reported protection against Borna disease after inoculation of high-dose cell-adapted BDV. Here we show that the outcome of the infection, i.e., immunopathology versus protection, is simply dependent on the amount of virus used for infection. High-dose BDV (10(6) FFU) triggers an early virus-specific reaction of the immune system, as demonstrated by strong cellular and humoral responses. In particular, the early presence and function of nucleoprotein-specific CD8(+) T cells could be demonstrated in the brain. We present evidence that in a noncytolytic and usually persistent virus infection, high-dose input virus mediates early control of the pathogen due to an efficient induction of an antiviral immune mechanism. From these data, we conclude that immune reactivity, in particular the cytotoxic T-cell response, determines whether the virus is controlled with prevention of the ensuing immunopathological disease or whether a persistent infection is established.
MeSH term(s)	Animals ; Borna Disease/immunology ; Dose-Response Relationship, Immunologic ; Female ; Male ; Nucleoproteins/immunology ; Rats ; Rats, Inbred Lew ; T-Lymphocytes, Cytotoxic/immunology
Chemical Substances	Nucleoproteins
Language	English
Publishing date	2001-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.75.23.11700-11708.2001
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Article: Brain cell lesions in Borna disease are mediated by T cells.

Bilzer, T / Stitz, L

Archives of virology. Supplementum

1993 Volume 7, Page(s) 153–158

Abstract: ... with monoclonal antibodies directed against CD4+ and CD8+ T cells could almost completely inhibit the immunopathological ... of antibody titers, brain cell destruction correlates well with the intracerebral presence of CD8+ T cells and ... can be destructed by T cell mediated cytotoxicity which results in organ atrophy and dementia. ...

Abstract	Experimental Borna Disease (BD) in rats is characterized by severe lymphocytic encephalitis and by massive brain cell lesions finally leading to brain atrophy. Treatment of BDV-infected rats with monoclonal antibodies directed against CD4+ and CD8+ T cells could almost completely inhibit the immunopathological reactions and revealed less BDV-infected neurons and astrocytes that expressed MHC class I antigen. Brain cell lesions were minimal, and no obvious brain atrophy could be observed even late after infection. Since BDV itself is not known to exert cytopathic effects and since brain cell damage was independent of antibody titers, brain cell destruction correlates well with the intracerebral presence of CD8+ T cells and the expression of MHC class I antigens. Moreover, BDV-infected brain cells in vitro could be demonstrated to be lysed in a MHC class I-restricted manner. These findings provide evidence that virus-infected neurons can be destructed by T cell mediated cytotoxicity which results in organ atrophy and dementia.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Borna Disease/immunology ; Borna Disease/pathology ; Brain/immunology ; Brain/microbiology ; Brain/pathology ; Rats ; T-Lymphocytes/immunology
Chemical Substances	Antibodies, Monoclonal
Language	English
Publishing date	1993
Publishing country	Austria
Document type	Journal Article ; Review
ZDB-ID	1318100-2
ISSN	0939-1983
ISSN	0939-1983
DOI	10.1007/978-3-7091-9300-6_12
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Article ; Online: Virus-specific CD4+ T cells eliminate Borna disease virus from the brain via induction of cytotoxic CD8+ T cells

Nöske, K. / Bilzer, T. / Planz, Oliver / Stitz, Lothar

1998

Abstract: ... with a virus-specific CD4(+) T cell line prior to infection. In rats receiving this treatment, only a transient ... hybridization for both genomic and mRNA, and by immunohistology, Most importantly, in vitro assays revealed that the T-cell line ... by the appearance of CD8(+) T cells and the expression of perforin in the brain. Testing of lymphocytes isolated ...

Abstract	Persistent Borna disease virus infection of the brain can be prevented by treatment of naive rats with a virus-specific CD4(+) T cell line prior to infection. In rats receiving this treatment, only a transient low-level encephalitis was seen compared to an increasingly inflammatory reaction in untreated infected control rats. Virus replication was found in the brain for several days after infection before the virus was cleared from the central nervous system. The loss of infectivity from the brain was confirmed by negative results by reverse transcription-PCR with primers for mRNA, by in situ hybridization for both genomic and mRNA, and by immunohistology, Most importantly, in vitro assays revealed that the T-cell line used for transfusion had no cytotoxic capacity. The kinetics of virus clearance were paralleled by the appearance of CD8(+) T cells and the expression of perforin in the brain. Testing of lymphocytes isolated from the brains of CD4(+) T-cell-treated rats after challenge revealed high cytotoxic activity due to the presence of CD8(+) cytotoxic T cells at time points when brain lymphocytes from infected control rats induced low-level cytolysis of target cells. Neutralizing antiviral antibodies and gamma interferon were shown not to be involved in the elimination of virus from the brain
Keywords	ddc:570
Subject code	570 ; 616
Language	English
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Virus-specific CD4+ T cells eliminate Borna disease virus from the brain via induction of cytotoxic CD8+ T cells

Nöske, K. / Bilzer, T. / Planz, Oliver / Stitz, Lothar

1998

Abstract	Persistent Borna disease virus infection of the brain can be prevented by treatment of naive rats with a virus-specific CD4(+) T cell line prior to infection. In rats receiving this treatment, only a transient low-level encephalitis was seen compared to an increasingly inflammatory reaction in untreated infected control rats. Virus replication was found in the brain for several days after infection before the virus was cleared from the central nervous system. The loss of infectivity from the brain was confirmed by negative results by reverse transcription-PCR with primers for mRNA, by in situ hybridization for both genomic and mRNA, and by immunohistology, Most importantly, in vitro assays revealed that the T-cell line used for transfusion had no cytotoxic capacity. The kinetics of virus clearance were paralleled by the appearance of CD8(+) T cells and the expression of perforin in the brain. Testing of lymphocytes isolated from the brains of CD4(+) T-cell-treated rats after challenge revealed high cytotoxic activity due to the presence of CD8(+) cytotoxic T cells at time points when brain lymphocytes from infected control rats induced low-level cytolysis of target cells. Neutralizing antiviral antibodies and gamma interferon were shown not to be involved in the elimination of virus from the brain
Keywords	Text ; ddc:570
Subject code	570 ; 616
Language	English
Publishing country	de
Document type	Article ; Online
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Article: Virus-specific CD4+ T cells eliminate Borna disease virus from the brain via induction of cytotoxic CD8+ T cells

Noske, K / Bilzer, T / Planz, O / Stitz, L

Journal of virology. May 1998. v. 72 (5)

1998

Keywords	rats ; immune response ; cell-mediated immunity ; CD8-positive T-lymphocytes ; CD4-positive T-lymphocytes
Language	English
Dates of publication	1998-05
Size	p. 4387-4395.
Document type	Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
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Article ; Online: Dystrophin (

Hilton, Stephanie / Christen, Matthias / Bilzer, Thomas / Jagannathan, Vidhya / Leeb, Tosso / Giger, Urs

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: Muscular dystrophy due to dystrophin deficiency in humans is phenotypically divided into a severe Duchenne and milder Becker type. Dystrophin deficiency has also been described in a few animal species, and ... ...

Abstract	Muscular dystrophy due to dystrophin deficiency in humans is phenotypically divided into a severe Duchenne and milder Becker type. Dystrophin deficiency has also been described in a few animal species, and few
MeSH term(s)	Animals ; Cats ; Female ; Male ; Cat Diseases/genetics ; Dystrophin/genetics ; Muscle Proteins/metabolism ; Muscle, Skeletal/metabolism ; Muscular Dystrophy, Duchenne/genetics ; Mutation, Missense
Chemical Substances	Dystrophin ; Muscle Proteins
Language	English
Publishing date	2023-02-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043192
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Article: Immune-mediated brain atrophy. CD8+ T cells contribute to tissue destruction during borna disease.

Bilzer, T / Stitz, L

Journal of immunology (Baltimore, Md. : 1950)

1994 Volume 153, Issue 2, Page(s) 818–823

Abstract: ... intraparenchymal CD8+ T cells, MHC class I Ags on Borna disease virus (BDV)-infected neurons, and numerous ... we provide evidence that the presence of CD8+ T cells within the brain parenchyma and the expression of MHC ... infected neurons in vivo can be destroyed by T cell-mediated cytotoxicity. ...

Abstract	Borna disease (BD) is a virus-induced immunopathologic disease of the central nervous system in a variety of species from birds to primates and probably in humans. Severe inflammatory reactions lead to tissue destruction and finally to cortical brain atrophy. After experimental infection of the rat, intraparenchymal CD8+ T cells, MHC class I Ags on Borna disease virus (BDV)-infected neurons, and numerous nerve cell lesions were present. Treatment of BDV-infected rats with the mAb OX-8 directed against CD8+ cells inhibited the immunopathologic reactions and reduced MHC class I Ag expression. Neuronal lesions were minimal and no loss of brain substance could be observed. Because BDV has no acute cytopathic effects, we provide evidence that the presence of CD8+ T cells within the brain parenchyma and the expression of MHC class I Ags on neurons play a major role for immunopathologic brain tissue destruction and virus-infected neurons in vivo can be destroyed by T cell-mediated cytotoxicity.
MeSH term(s)	Animals ; Atrophy ; Borna Disease/immunology ; Borna Disease/pathology ; Brain/immunology ; Brain/pathology ; CD4-Positive T-Lymphocytes/immunology ; CD8 Antigens/analysis ; Histocompatibility Antigens Class I/analysis ; Rats ; Rats, Inbred Lew ; T-Lymphocyte Subsets/immunology
Chemical Substances	CD8 Antigens ; Histocompatibility Antigens Class I
Language	English
Publishing date	1994-07-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
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