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3.
Nat Med ; 7(6): 725-31, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11385511

RESUMO

Surface-contact-mediated signaling induced by the measles virus (MV) fusion and hemagglutinin glycoproteins is necessary and sufficient to induce T-cell unresponsiveness in vitro and in vivo. To define the intracellular pathways involved, we analyzed interleukin (IL)-2R signaling in primary human T cells and in Kit-225 cells. Unlike IL-2-dependent activation of JAK/STAT pathways, activation of Akt kinase was impaired after MV contact both in vitro and in vivo. MV interference with Akt activation was important for immunosuppression, as expression of a catalytically active Akt prevented negative signaling by the MV glycoproteins. Thus, we show here that MV exploits a novel strategy to interfere with T-cell activation during immunosuppression.


Assuntos
Tolerância Imunológica , Vírus do Sarampo/imunologia , Sarampo/imunologia , Proteínas do Leite , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas/metabolismo , Receptores de Interleucina-2/metabolismo , Transdução de Sinais/fisiologia , Linfócitos T/imunologia , Androstadienos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Linhagem Celular , Cromonas/farmacologia , Proteínas de Ligação a DNA/metabolismo , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Hemaglutininas Virais/metabolismo , Humanos , Interleucina-2/metabolismo , Janus Quinase 1 , Janus Quinase 3 , Ativação Linfocitária , Sarampo/virologia , Vírus do Sarampo/metabolismo , Vírus do Sarampo/efeitos da radiação , Camundongos , Camundongos Transgênicos , Morfolinas/farmacologia , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/imunologia , Proteínas Proto-Oncogênicas c-akt , Fator de Transcrição STAT3 , Fator de Transcrição STAT5 , Sigmodontinae , Baço/citologia , Linfócitos T/enzimologia , Linfócitos T/metabolismo , Transativadores/metabolismo , Proteínas Virais de Fusão/metabolismo , Wortmanina , Proteína de Morte Celular Associada a bcl
4.
J Exp Med ; 166(1): 259-64, 1987 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-3036995

RESUMO

Inducibility of Ia molecules on cultivated astrocytes by JHM virus correlates with demyelinating disease susceptibility of animals from which these astrocytes are derived. On the contrary, class I induction of both astrocytes and oligodendrocytes occurs as a consequence of normal cultivation procedures in both susceptible and resistant strains. Increased expression of class I antigens on rat astrocytes and oligodendrocytes is not related to JHM viral infection as it is in the mouse. These data indicate that strain differences in Ia inducibility, rather than inducibility of class I antigens, by JHM virus may explain higher levels of T cell-mediated damage to myelin during infection in susceptible rat strains compared with resistant strains.


Assuntos
Astrócitos/imunologia , Infecções por Coronaviridae/imunologia , Encefalite/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Acetilmuramil-Alanil-Isoglutamina/imunologia , Animais , Coronaviridae/imunologia , Doenças Desmielinizantes/imunologia , Regulação da Expressão Gênica , Antígenos de Histocompatibilidade/genética , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew
5.
J Exp Med ; 173(5): 1235-46, 1991 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-1827142

RESUMO

The potential of cells within the central nervous system (CNS) to initiate T lymphocyte responses is not known and was the subject of this study. Using the ability of virgin T lymphocytes to proliferate in a primary response to allogeneic determinants on antigen-presenting cells (APC), we have examined the capacity of major histocompatibility complex (MHC)-expressing astroglial cells to act as stimulators of primary and secondary T cell responses. Neither freshly isolated astrocytes nor primary astrocyte cultures pretreated with interferon gamma (IFN-gamma) to upregulate MHC class I and II expression stimulated unfractionated lymph node (LN) cell populations in the primary mixed lymphocyte reaction. In mixing experiments, astrocytes did not inhibit the T cell response to allogeneic LN stimulators. Purified responder CD4+ T cells also were not stimulated to proliferate or secrete interleukin 2 (IL-2) by MHC class I- and II-expressing astrocytes. In contrast to their inability to stimulate virgin, alloreactive CD4+ T cells, astrocytes were able to specifically stimulate an alloreactive CD4+ T cell line. Unprimed CD8+ T cells, however, exhibited some weak autonomous proliferation to astrocyte stimulators but this response was only substantial in the presence of exogenous IL-2, the latter predominantly being a CD4+ T cell product. Those CD8+ T cells responding in the presence of IL-2 were mainly T cell receptor alpha/beta+ IL-2 receptor (alpha chain)+, and a majority had shifted from high to low CD45R expression. Given the virtual dependence of CD8+ T cells in these studies, on CD4+ T cell help, and the complete absence of activation of this latter subset by astrocytes, it is clear that in the context of this resident CNS cell, further activation of either T cell subset by astrocytes within the CNS can only follow priming by another type of APC. The implications of these results for the induction of T cell responses in the CNS are discussed.


Assuntos
Astrócitos/imunologia , Sistema Nervoso Central/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Neuroglia/imunologia , Linfócitos T Auxiliares-Indutores/fisiologia , Linfócitos T Reguladores/fisiologia , Animais , Astrócitos/metabolismo , Astrócitos/fisiologia , Antígenos CD4/imunologia , Sistema Nervoso Central/citologia , Sistema Nervoso Central/fisiologia , Feminino , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Interferon gama/farmacologia , Interleucina-2/metabolismo , Interleucina-2/fisiologia , Complexo Principal de Histocompatibilidade/fisiologia , Neuroglia/metabolismo , Neuroglia/fisiologia , Gravidez , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/fisiologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
6.
J Exp Med ; 177(4): 1145-52, 1993 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-8459208

RESUMO

A flow cytometric phenotype for isolated adult central nervous system (CNS) ramified microglia was previously defined (CD45low CD11b/c+) in the Lewis strain rat, that clearly distinguished these cells from all blood-derived leucocytes, the latter being CD45high. Consistent with the reported lack of major histocompatibility complex (MHC) expression in the CNS, isolated microglia were mostly MHC class II-. Employing these phenotypic criteria, we now show that a proportion of microglia in Brown Norway (BN) strain rats are constitutively MHC class II+. In spinal cord, up to 25% of microglia are distinctly positive and most have some level of expression. In situ staining of MHC class II+ microglial cells in BN rats indicates that positive cells are typical of ramified microglia on the grounds of both morphological appearance and anatomical location. In Lewis (LEW) rats, the few MHC class II-expressing cells isolated from the normal CNS are CD45high blood-derived cells and not resident microglia. After infection of both LEW and BN rats with a neurotropic murine hepatitis virus (MHV-JHM), MHC class II was rapidly upregulated on microglia in the BN but not in the LEW strain. In the latter, inflammatory cells were the predominant MHC class II-expressing population. Nevertheless, most microglia in the LEW strain could, after some delay, be induced to express MHC class II after transfer of an experimental autoimmune encephalomyelitis (EAE)-inducing encephalitogenic T cell line. Paradoxically, strains resistant to EAE (exemplified by the BN) contained more constitutive MHC class II-expressing microglia than susceptible ones, when a variety of strains were examined. The results clearly establish that the normal CNS may contain MHC class II-expressing cells that are a resident rather than a transient blood-derived population. It is significant that this expression is strain related, but there is no evidence that microglial cell constitutive MHC class II expression predisposes to EAE susceptibility.


Assuntos
Sistema Nervoso Central/citologia , Antígenos de Histocompatibilidade Classe II/imunologia , Macrófagos/imunologia , Neuroglia/imunologia , Animais , Sistema Nervoso Central/imunologia , Quimera , Encefalomielite/imunologia , Feminino , Imunidade Inata , Camundongos , Fenótipo , Ratos , Ratos Endogâmicos Lew , Regulação para Cima
7.
J Neural Transm (Vienna) ; 117(6): 699-705, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20454983

RESUMO

Central dopaminergic (DA) systems are affected during human immunodeficiency virus (HIV) infection. So far, it is believed that they degenerate with progression of HIV disease because deterioration of DA systems is evident in advanced stages of infection. In this manuscript we found that (a) DA levels are increased and DA turnover is decreased in CSF of therapy-naïve HIV patients in asymptomatic infection, (b) DA increase does not modulate the availability of DA transporters and D2-receptors, (c) DA correlates inversely with CD4+ numbers in blood. These findings show activation of central DA systems without development of adaptive responses at DA synapses in asymptomatic HIV infection. It is probable that DA deterioration in advanced stages of HIV infection may derive from increased DA availability in early infection, resulting in DA neurotoxicity. Our findings provide a clue to the synergism between DA medication or drugs of abuse and HIV infection to exacerbate and accelerate HIV neuropsychiatric disease, a central issue in the neurobiology of HIV.


Assuntos
Dopamina/metabolismo , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Transmissão Sináptica/fisiologia , Ácido 3,4-Di-Hidroxifenilacético/líquido cefalorraquidiano , Adulto , Benzamidas , Antígenos CD4/metabolismo , Estudos de Casos e Controles , Quimiocina CCL2/metabolismo , Galactosefosfatos/metabolismo , HIV/genética , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/diagnóstico por imagem , Infecções por HIV/imunologia , Ácido Homovanílico/líquido cefalorraquidiano , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tropanos , Carga Viral/métodos
8.
J Neural Transm Suppl ; (72): 317-22, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17982909

RESUMO

In this study we investigated differences in the gene expression profiling of the brains of rhesus macaques that were uninfected or infected with SIV in the asymptomatic stage or AIDS. The main aim was to use biostatistical methods to classify brain gene expression following SIV infection, without consideration of the biological significance of the individual genes. We also used data from animals treated with different pharmacological substances such as dopaminergic drugs, N-methyl-D-aspartate (NMDA) antagonists or antioxidants during the early stage of infection as these animals exhibited an accelerated or attenuated neuropsychiatric disease progression. We found macaque subspecies to be a more important factor for disease classification based on gene expression profiling than clinical symptoms or neuropathological findings. It is noteworthy that SIV-infected pharmacologically-treated. Chinese animals clustered near uninfected animals independent on the outcome of the treatment, whereas untreated SIV infected animals were clustered in a separate subtree. It is clear from this study that NeuroAIDS is a diverse disease entity and that SIV brain genes can be differentially regulated, depending on the disease type as well as changed dependent on the monkey subspecies.


Assuntos
Biometria/métodos , Encéfalo/virologia , Perfilação da Expressão Gênica/estatística & dados numéricos , Macaca mulatta/genética , Análise de Sequência com Séries de Oligonucleotídeos/estatística & dados numéricos , Síndrome de Imunodeficiência Adquirida dos Símios/genética , Vírus da Imunodeficiência Símia/genética , Algoritmos , Animais , Teorema de Bayes , China , Análise por Conglomerados , Progressão da Doença , Encefalite Viral/genética , Encefalite Viral/virologia , Regulação Viral da Expressão Gênica/fisiologia , Índia , Modelos Lineares , Putamen/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Especificidade da Espécie , Viremia/genética , Viremia/virologia , Replicação Viral/genética
9.
Curr Top Microbiol Immunol ; 276: 77-101, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12797444

RESUMO

Measles is a major cause of childhood mortality in developing countries which is mainly attributed to the ability of measles virus (MV) to suppress general immune responses. Paradoxically, virus-specific immunity is efficiently induced, which leads to viral clearance from the host and confers long-lasting protection against reinfection. As sensitisers of pathogen encounter and instructors of the adaptive immune response, dendritic cells (DCs) may play a decisive role in the induction and quality of the MV-specific immune activation. The ability of MV wild-type strains in particular to infect DCs in vitro is dearly established, and the receptor binding haemagglutinin protein of these viruses essentially determines this particular tropism. DC maturation as induced early after MV infection is likely to be of crucial importance for the induction of MV-specific immunity. DCs may, however, be instrumental in MV-induced immunosuppression. (1) T cell depletion could be brought about by DC-T cell fusion or TRAIL-mediated induction of apoptosis. (2) Inhibition of stimulated IL-12 production from MV-infected DCs might affect T cell responses in qualitative terms in favouring Th2 and suppressing Th1 responses. (3) The viral glycoprotein complex expressed at high levels on infected DCs late in infection is able to directly inhibit T cell proliferation by surface contact-dependent negative signalling. This most likely accounts for the failure of infected DC cultures to stimulate allogeneic and inhibit mitogen-stimulated T cell proliferation in vitro and the pronounced proliferative unresponsiveness of T cell ex vivo to polyclonal and antigen-specific stimulation which is a central finding of MV-induced immunosuppression.


Assuntos
Células Dendríticas/imunologia , Vírus do Sarampo/fisiologia , Sarampo/imunologia , Receptores Virais/fisiologia , Células Dendríticas/virologia , Humanos , Vírus do Sarampo/classificação , Vírus do Sarampo/imunologia , Vírus do Sarampo/patogenicidade , Proteínas Virais/fisiologia
10.
Curr Mol Med ; 1(2): 163-81, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11899069

RESUMO

A profound, transient suppression of immune functions during and after the acute infection is the major cause of more than one million cases of infant deaths associated with measles worldwide. Concommittant with the generation of an efficient measles virus (MV) specific immunity, immune responses towards other pathogens are strongly impaired and provide the basis for the establishment and severe course of opportunistic infections. The molecular basis for MV-induced immunosuppression has not been resolved as yet. Similar to other immunosuppressive viruses, MV is lymphotropic and viral nucleic acid and proteins are detectable in peripheral blood mononuclear cells (PBMC). It is considered central to MV-induced immunosuppression that PBMC isolated from patients largely fail to proliferate in response to antigen specific and polyclonal stimulation. The low abundancy of MV-infected PBMC suggests that MV-induced immunosuppression is not directly caused by infection-mediated cell loss or fusion, but rather by indirect mechanisms such as deregulation of cytokines or surface contact-mediated signaling which may lead to apoptosis or impair the proliferative response of uninfected PBMC. Evidence for a role of any of these mechanisms was obtained in vitro, however, much has still to be learned about the tropism of MV and its interactions with particular host cells such as dendritic cells in vivo.


Assuntos
Tolerância Imunológica , Vírus do Sarampo/imunologia , Sarampo/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Antígenos CD/metabolismo , Morte Celular/fisiologia , Humanos , Linfócitos/fisiologia , Sarampo/fisiopatologia , Vírus do Sarampo/fisiologia , Proteína Cofatora de Membrana , Glicoproteínas de Membrana/metabolismo , Modelos Imunológicos , Transdução de Sinais/fisiologia
11.
Microbes Infect ; 2(14): 1687-92, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11137042

RESUMO

In the present study we describe a live vaccine against measles virus (MV) infection on the basis of attenuated Salmonella typhimurium aroA secreting MV antigens via the Escherichia coli alpha-hemolysin secretion system. Two well-characterized MV epitopes, a B-cell epitope of the MV fusion protein (amino acids 404-414) and a T-cell epitope of the MV nucleocapsid protein (amino acids 79-99) were fused as single or repeating units to the C-terminal secretion signal of the E. coli hemolysin and expressed in secreted form by the attenuated S. typhimurium aroA SL7207. Immunization of MV-susceptible C3H mice revealed that S. typhimurium SL7207 secreting these antigens provoked a humoral and a cellular MV-specific immune response, respectively. Mice vaccinated orally with a combination of both recombinant S. typhimurium strains showed partial protection against a lethal MV encephalitis after intracerebral challenge with a rodent-adapted, neurotropic MV strain.


Assuntos
Epitopos de Linfócito B/biossíntese , Epitopos de Linfócito T/biossíntese , Vírus do Sarampo/imunologia , Salmonella , Panencefalite Esclerosante Subaguda/prevenção & controle , Vacinas Virais , Administração Oral , Sequência de Aminoácidos , Animais , Sequência de Bases , Vetores Genéticos , Camundongos , Camundongos Endogâmicos C3H , Dados de Sequência Molecular , Plasmídeos , Proteínas Recombinantes/imunologia
12.
Neurology ; 56(7): 938-43, 2001 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-11294933

RESUMO

BACKGROUND: Natural infections bear the risk of triggering MS bouts, whereas epidemiologic studies have not delineated an increased risk for disease activity after influenza virus vaccination. OBJECTIVE: To examine influenza A virus-specific and myelin protein-reactive T-cell frequencies by interferon gamma (IFNgamma)-enzyme-linked immunospot and the response of these cells by IFNgamma-reverse transcription (RT) PCR after immunization and any incidental upper respiratory tract infection (URI) in 12 patients with MS (seven with a relapsing-remitting course; five with a secondary progressive course; Kurtzke Expanded Disability Status Scale [EDSS] score from 1.0 to 6.5, without immunosuppressive treatment) and 28 healthy volunteers. RESULTS: A cellular immune response against influenza A virus was mounted in both populations at 2 weeks after vaccination. Patients with MS showed a higher relative increase (p = 0.008) than controls with respect to the number of influenza-specific T cells. Mean antibody responses against influenza A virus were increased in both populations after 2 weeks (p < 0.01). Despite these virus-specific reactions, no increase in T-cell frequencies responsive to human myelin basic protein (MBP) or recombinant human myelin oligodendrocyte protein (MOG) was observed after immunization, arguing against a general immune stimulation by influenza vaccination. In contrast, MBP-specific T-cell responses became detectable in several individuals after febrile infection. CONCLUSION: These data support the clinical observations that influenza vaccination is effective and safe in patients with MS with respect to cellular immunoreactivity against two main CNS myelin proteins.


Assuntos
Encéfalo/imunologia , Vacinas contra Influenza/imunologia , Esclerose Múltipla/imunologia , Linfócitos T/imunologia , Vacinação , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
J Neuroimmunol ; 19(1-2): 69-75, 1988 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2456308

RESUMO

We have recently observed strain differences in interferon-gamma (IFN-gamma) induction of Ia on astrocytes in rats and mice that are susceptible or resistant to experimental allergic encephalomyelitis (EAE) (Massa et al., 1987). We now found that keratinocytes cultured from rat skin show the same strain differences as astrocytes. Keratinocytes of EAE-susceptible Lewis rats are induced to higher levels of Ia expression compared to relatively resistant Brown-Norway (BN) rats, independent of the dose of IFN-gamma applied. This difference in regulation is specific for class II histocompatibility molecules because no such differences are seen with class I antigen induction by IFN-gamma. That keratinocytes reflect similar strain differences as astrocytes may be explained by a common ectodermal origin of these epithelial-like cells. This observation allows the determination of the genetic predisposition of an autoimmune response in the central nervous system by skin biopsy. This approach may be of importance in studies of immunopathological phenomena of brain tissue in man such as multiple sclerosis.


Assuntos
Astrócitos/imunologia , Encéfalo/imunologia , Genes MHC da Classe II , Antígenos de Histocompatibilidade Classe II/imunologia , Pele/imunologia , Animais , Células Cultivadas , Citometria de Fluxo , Técnicas Imunoenzimáticas , Interferon gama/farmacologia , Queratinas/análise , Camundongos , Esclerose Múltipla/imunologia , Ratos , Ratos Endogâmicos , Pele/citologia
14.
J Neuroimmunol ; 7(2-3): 77-89, 1984 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6511890

RESUMO

A technique is described which allows the detection of virus-specific oligoclonal IgG in unconcentrated cerebrospinal fluid (CSF) from patients with virus infections of the central nervous system. CSF is isoelectrically focused in agarose gels and immunoglobulins are blotted to nitrocellulose filters, passively loaded with either anti-human IgG or viral antigen. Transferred total IgG, as well as virus-specific IgG, is identified by the use of peroxidase-labelled anti-human IgG and 4-chloro-1-naphthol as a precipitating peroxidase substrate. Application of this assay in cases of SSPE, mumps meningitis and herpes simplex encephalitis demonstrates sensitivity and possible suitability of this technique for use in diagnosis of virus infections of the CNS.


Assuntos
Anticorpos Antivirais/líquido cefalorraquidiano , Imunoglobulina G/líquido cefalorraquidiano , Viroses/líquido cefalorraquidiano , Adolescente , Adulto , Anticorpos Antivirais/isolamento & purificação , Antígenos Virais/imunologia , Colódio , Encefalite/líquido cefalorraquidiano , Encefalite/imunologia , Feminino , Herpes Simples/líquido cefalorraquidiano , Herpes Simples/imunologia , Humanos , Imunoglobulina G/isolamento & purificação , Imunoglobulinas/líquido cefalorraquidiano , Imunoglobulinas/isolamento & purificação , Focalização Isoelétrica , Meningite Viral/líquido cefalorraquidiano , Meningite Viral/imunologia , Caxumba/líquido cefalorraquidiano , Caxumba/imunologia , Vírus da Caxumba/imunologia , Bandas Oligoclonais , Vírus SSPE/imunologia , Panencefalite Esclerosante Subaguda/líquido cefalorraquidiano , Panencefalite Esclerosante Subaguda/imunologia , Viroses/imunologia
15.
J Neuroimmunol ; 46(1-2): 217-23, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7689589

RESUMO

The questions how a viral infection induces cellular autoimmune reactions (CMAI) and which components of both virus and auto-antigen play part in this process were addressed in our animal model of measles virus (MV)-induced CMAI against myelin basic protein (MBP) during subacute measles encephalitis (SAME). In an attempt to define whether cellular or humoral immune responses are involved in the occurrence of the autoimmune based disease process, Lewis rats were treated with different combinations of antibodies and T cells reactive with either MV and its structural proteins or MBP and MBP-peptides. The only treatment combination after which experimental allergic encephalomyelitis (EAE)-like disease and pathology developed was when non-encephalitogenic T cells reactive against residues 69-81 of MBP were adoptively transferred into MV-infected Lewis rats. The results of the study show that T cells which are non-encephalitogenic in the normal central nervous tissue are capable of inducing an allergic encephalomyelitis in animals with a viral infection involving the brain.


Assuntos
Anticorpos Antivirais/imunologia , Encefalomielite Autoimune Experimental/complicações , Sarampo/complicações , Proteína Básica da Mielina/imunologia , Linfócitos T/imunologia , Sequência de Aminoácidos , Animais , Autoanticorpos/imunologia , Encefalomielite Autoimune Experimental/imunologia , Imunização Passiva , Ativação Linfocitária , Dados de Sequência Molecular , Proteína Básica da Mielina/química , Peptídeos/imunologia , Ratos , Ratos Endogâmicos Lew
16.
J Neuroimmunol ; 13(3): 259-71, 1987 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3025254

RESUMO

Viral particles of a neurotropic murine hepatitis virus (JHM) and various substances known to have immunoregulatory effects, including bacterial lipopolysaccharide (LPS) and synthetic adjuvant peptide (muramyl dipeptide) (AP), were tested for their ability to induce Ia antigen expression on Lewis rat astrocytes in vitro. JHM virus, LPS and AP are all capable of inducing Ia molecules on astrocytes, however, in a pattern and kinetics distinct from recombinant rat gamma interferon (gamma-IFN). Whereas gamma-IFN induced Ia expression on astrocytes and all macrophages after 48 h treatment, JHM virus, LPS and AP required 4-7 days for maximal induction of Ia on astrocytes, but had little to no effect on the macrophage population. This indicates that astrocytes are uniquely reactive to components derived from infectious agents and that these components are immunoregulatory with respect to Ia expression on astrocytes. We have also attempted to determine possible mechanisms by which these agents induce astrocyte Ia and show that phorbol myristate acetate and Ca2+ ionophore A23187 have similar effects. These findings suggest that infectious agents may directly stimulate antigen presenting functions of astrocytes in the brain through gamma-IFN-independent mechanisms.


Assuntos
Acetilmuramil-Alanil-Isoglutamina/farmacologia , Astrócitos/imunologia , Tronco Encefálico/imunologia , Antígenos de Histocompatibilidade Classe II/biossíntese , Vírion/imunologia , Animais , Ácido Araquidônico , Ácidos Araquidônicos/metabolismo , Astrócitos/efeitos dos fármacos , Calcimicina/farmacologia , Cálcio/fisiologia , Imunofluorescência , Histocitoquímica , Técnicas In Vitro , Interferon gama/imunologia , Lipopolissacarídeos/farmacologia , Vírus da Hepatite Murina/imunologia , Proteína Quinase C/metabolismo , Ratos , Ratos Endogâmicos Lew
17.
J Neuroimmunol ; 6(5): 325-36, 1984 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-6086712

RESUMO

Temperature-sensitive mutants of the murine coronavirus JHM induced a subacute demyelinating encephalomyelitis (SDE) in young rats. Neurological symptoms were associated with marked lesions of primary demyelination in the white matter of the central nervous system (CNS), and developing after an incubation time of several weeks to months. Many rats survived this infection and recovered completely from this CNS disease. Among 43 survivors of SDE, 9 rats developed a relapse 27-153 days after onset of the first attack. Neuropathological examination of these animals revealed areas of fresh demyelination together with old remyelinated lesions. Viral antigens were detectable in the neighbourhood of fresh lesions and in some cases infectious virus was re-isolated from rats revealing low antibody titers to JHM virus. These results demonstrate that mutants of JHM virus can induce a relapsing demyelinating disease process, associated with a persistent infection, which possesses some similarities to chronic experimental allergic encephalomyelitis.


Assuntos
Infecções por Coronaviridae , Encefalomielite/etiologia , Animais , Antígenos Virais/análise , Tronco Encefálico/patologia , Efeito Citopatogênico Viral , Doenças Desmielinizantes/complicações , Encefalomielite/complicações , Neuroglia/imunologia , Ratos , Recidiva , Medula Espinal/patologia
18.
J Neuroimmunol ; 19(4): 339-52, 1988 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3262624

RESUMO

The intrathecal humoral immune response was analysed in patients with subacute sclerosing panencephalitis (SSPE) and Lewis rats with subacute measles virus (MV)-induced encephalomyelitis (SAME). SSPE patients as well as SAME rats revealed oligoclonal, intrathecal antibody synthesis with MV specificity. SAME rats synthesized MV-specific antibodies intracerebrally to a higher extent than SSPE patients. Although a restricted isoelectric pattern of MV-specific antibodies was detected in the cerebrospinal fluid (CSF) of SSPE patients as well as of SAME rats, the heterogeneity within clusters of immunoglobulin bands was higher in the rat specimens. Increase in the blood-brain barrier permeability for albumin was exclusively detected in SAME rats but not in SSPE patients. These data suggest that the rat model offers excellent opportunities to study the initial humoral events in MV-induced encephalitides.


Assuntos
Anticorpos Antivirais/imunologia , Encefalomielite/etiologia , Imunoglobulinas/imunologia , Vírus do Sarampo/imunologia , Panencefalite Esclerosante Subaguda/imunologia , Animais , Anticorpos Antivirais/análise , Anticorpos Antivirais/líquido cefalorraquidiano , Especificidade de Anticorpos , Barreira Hematoencefálica , Encefalomielite/sangue , Encefalomielite/imunologia , Humanos , Focalização Isoelétrica , Sistema Nervoso/patologia , Ratos , Ratos Endogâmicos Lew , Panencefalite Esclerosante Subaguda/sangue , Panencefalite Esclerosante Subaguda/líquido cefalorraquidiano
19.
J Neuroimmunol ; 17(2): 103-18, 1988 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2447122

RESUMO

Intracerebral inoculation of weanling Lewis rats with measles virus led to the development of subacute measles encephalomyelitis (SAME) 4-8 weeks after infection. The disease is characterized pathologically by an intense inflammatory infiltration within both the white and grey matter of the central nervous system (CNS) without apparent demyelination. Both during and after SAME splenic lymphocytes from these animals could be restimulated in vitro to proliferate in the presence of myelin base protein (MBP). MBP-specific class II MHC-restricted T cell lines were isolated from this cell population. They were shown to exhibit no cross-reactivity with measles virus and to induce experimental allergic encephalitis (EAE) in naive syngeneic recipients following adoptive transfer. The clinical and histopathological signs of this T cell-mediated disease were identical to that seen in classical T cell-mediated EAE. A humoral immune response to MBP was only detected in a limited number of those rats with SAME. These results indicate that autoimmune reactions to brain antigen can arise during measles virus infection which may contribute to the pathogenesis of measles virus-associated encephalomyelitis.


Assuntos
Doenças Autoimunes/etiologia , Encefalite/etiologia , Encefalomielite Autoimune Experimental/etiologia , Sarampo/complicações , Proteína Básica da Mielina/imunologia , Animais , Anticorpos Antivirais/biossíntese , Autoanticorpos/biossíntese , Doenças Autoimunes/patologia , Encefalite/imunologia , Encefalite/patologia , Encefalomielite Autoimune Experimental/patologia , Imunização Passiva , Ativação Linfocitária , Proteína Básica da Mielina/toxicidade , Ratos , Ratos Endogâmicos Lew , Linfócitos T/imunologia , Linfócitos T/transplante
20.
J Neuroimmunol ; 12(2): 131-42, 1986 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3016024

RESUMO

The humoral intrathecal immune response in coronavirus-induced demyelinating encephalomyelitis in rats associated with an autoimmune reaction to brain antigen, was analysed. The CSF of these animals revealed immune reactions which were directed against coronavirus and other, unknown, antigens. In general, no direct correlation between the disease, the state of the blood-brain barrier (BBB), intrathecal synthesis of Ig and the presence of virus-specific antibodies was detectable, suggesting that the humoral, in contrast to the cellular, immune response does not play a significant pathogenetic role in this CNS disease.


Assuntos
Anticorpos Antivirais/análise , Infecções por Coronaviridae/imunologia , Doenças Desmielinizantes/imunologia , Encefalomielite/imunologia , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/líquido cefalorraquidiano , Barreira Hematoencefálica , Coronaviridae/imunologia , Encefalomielite/etiologia , Ratos
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