Major Histocompatibility Complex Class I Expression on Neurons in Subacute Sclerosing Panencephalitis and Experimental Subacute Measles Encephalitis

Gogate, Nitin; Swoveland, Peggy; Yamabe, Toshio; Verma, Lalit; Woyciechowska, Joanna; Tarnowska-Dziduszko, E; Dymecki, J; Dhib‐Jalbut, Suhayl

doi:10.1097/00005072-199604000-00006

Cited by 27 publications

(16 citation statements)

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“…This indicates that neurons can be a target of CTL, which therefore may play a role in disorders hallmarked by nerve cell degeneration and death. This is consistent with an observation of MHC class I expression in neurons in brains from patients with subacute sclerosing encephalitis [Gogate et al, 1996]. In this study only a small proportion of the measles virus-infected neurons expressed MHC class I antigen, which may suggest that such cells are cleared rapidly by the CTL.…”

Section: The Role Of Functional Mhc Class I-mediated Antigen-presentisupporting

confidence: 93%

Spread of measles virus through axonal pathways into limbic structures in the brain of TAP1 ‐/‐ mice

Urbańska

Chambers

Ljunggren

et al. 1997

Journal of Medical Virology

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The spread of measles virus into the brain was studied exploiting the olfactory pathway, which represents an important route of neuroinvasion by viruses. The virus was injected into the main olfactory bulb of wild-type mice and mice with disrupted TAP1 gene (TAP refers to the Transporter associated with Antigen Presentation), which codes for products essential for the cell-mediated immune response. Virus invasion was monitored for 4 weeks by immunohistochemistry. The distribution of measles virus was found to be restricted to brain areas connected with the olfactory bulbs. However, in the wild-type mice there was a marked infiltration of lymphocytes in the infected brain structures, and the virus did not pass beyond the piriform cortex. In the TAP1 -/- mice the virus spread more extensively along olfactory projections into the limbic system and monoaminergic brainstem neurons. Infected mice of both types developed seizures, which may have been focally evoked from the piriform cortex. This study provides evidence that measles virus can spread through axonal pathways in the brain. The findings obtained in the gene-manipulated mice point out that a compromised immune state of the host may potentiate targeting of virus to the limbic system through olfactory projections.

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Section: The Role Of Functional Mhc Class I-mediated Antigen-presentisupporting

confidence: 93%

Spread of measles virus through axonal pathways into limbic structures in the brain of TAP1 ‐/‐ mice

Urbańska

Chambers

Ljunggren

et al. 1997

Journal of Medical Virology

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“…These data suggest that infiltrating T cells in the NSE-CD46 model are not constitutively producing antiviral cytokines within the CNS and that this scenario is unlikely. (ii) Previous reports have shown that class I MHC can be induced on CNS neurons in response to injury (28,29,31,32,54) or virus infection, including MV (11,13). Thus, while class I and II MHC expression may be below detection limits in the uninfected brain, MV infection may induce expression, allowing for MHC-T-cell receptor contact to occur.…”

Section: Discussionmentioning

confidence: 99%

Immune-Mediated Protection from Measles Virus-Induced Central Nervous System Disease Is Noncytolytic and Gamma Interferon Dependent

Patterson

Lawrence

Echols

et al. 2002

J Virol

142

175

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Neurons of the mammalian central nervous system (CNS) are an essential and largely nonrenewable cell population. Thus, virus infections that result in neuronal depletion, either by virus-mediated cell death or by induction of the cytolytic immune response, could cause permanent neurological impairment of the host. In a transgenic mouse model of measles virus (MV) infection of neurons, we have previously shown that the host T-cell response was required for resolution of infection in susceptible adult mice. In this report, we show that this protective response did not result in neuronal death, even during the peak of T-cell infiltration into the brain parenchyma. When susceptible mice were intercrossed with specific immune knockout mice, a critical role for gamma interferon (IFN-␥) was identified in protection against MV infection and CNS disease. Moreover, the addition of previously activated splenocytes or recombinant murine IFN-␥ to MV-infected primary neurons resulted in the inhibition of viral replication in the absence of neuronal death. Together, these data support the hypothesis that the host immune response can promote viral clearance without concomitant neuronal loss, a process that appears to be mediated by cytokines.

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“…Membranes were prehybridized in 0.25 M Na 2 HPO 4 (pH 7.2), 10% SDS, 1 mM EDTA, and 2% blocking reagent at 68°C for 3 h. Hybridization was carried out in the same buffer containing 20 ng of the DIG-labeled cRNA probe per ml at 68°C for 16 h. After hybridization, membranes were washed three times for 20 min for each wash in 25 mM Na 2 HPO 4 (pH 7.2), 1% SDS, and 1 mM EDTA at 68°C. The hybridization signal was detected on X-ray film by using alkaline phosphataseconjugated anti-DIG antibody and disodium 3-(4-methoxyspiro{1,2-dioxetane-3,2Ј-(5Ј-chloro)tricyclo[3.3.1.1 3,7 ]decan}-4-yl)phenyl phosphate (CSPD) chemiluminescent substrate (Boehringer Mannheim). Quantitative analysis of the autoradiograms was performed using NIH Image 1.61 software.…”

Section: Methodsmentioning

confidence: 99%

The Role of CD8⁺T Cells and Major Histocompatibility Complex Class I Expression in the Central Nervous System of Mice Infected with Neurovirulent Sindbis Virus

Kimura

Griffin

2000

J Virol

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Little is known about the role of CD8 ؉ T cells infiltrating the neural parenchyma during encephalitis induced by neurovirulent Sindbis virus (NSV). NSV preferentially infects neurons inSindbis virus (SV), an alphavirus in the family Togaviridae, causes acute encephalomyelitis in mice. Neuroadapted Sindbis virus (NSV) is a neurovirulent strain of SV that can elicit fatal encephalitis in adult mice as well as in suckling mice and provides a model system for examining the factors that determine outcome (11). Antibodies play a crucial role in the clearance of infectious virus from the central nervous system (CNS) of SV-infected mice (23), but infection also induces a brisk mononuclear inflammatory response that is immunologically specific and includes both CD4 ϩ and CD8 ϩ lymphocytes (13,26,28). Little is known about the role of T cells infiltrating the neural parenchyma in the pathogenesis of NSV-induced encephalomyelitis. By adoptive transfer, virus-specific antibody can protect mice from fatal infection with NSV when given before or after infection, while T cells are not protective (11,12,43). However, preimmunization with the nonstructural proteins of SV protects mice from fatal NSV encephalitis by a mechanism that appears to be dependent on T cells (8).The primary target cells for NSV infection in the CNS are neurons (15, 16). If neurons could express functional major histocompatibility complex (MHC) class I molecules, then infected neurons could be recognized by CD8 ϩ T cells and be targets for cytotoxic processes. Such a mechanism for neuronal damage could be involved in fatal disease induced by neurotropic virus infection. The ability of neurons to express class I molecules remains controversial. Tissues of the nervous system and primary cultures of neurons do not express detectable levels of MHC class I molecules normally (20,21,30,48). However, MHC class I expression can be induced in neuronal cell lines (5, 19) and cultured neurons (32,33,39,50,51) by gamma interferon treatment. Recent studies have described neuronal class I expression in vivo. In rats, constitutive expression of class I antigen has been detected in motoneurons, and this expression was increased following axotomy (24). In the developing cat brain, expression of class I mRNA and protein in neurons of the lateral geniculate nucleus correlates closely with synaptic remodelling of the visual system (2).In this study, we first investigated whether NSV-infected neurons expressed MHC class I as determined by immunohistochemistry and in situ hybridization. Subsequently, we analyzed the disease course in mice that genetically lack functional CD8 ϩ cytolytic T lymphocytes to determine whether CD8 ϩ T cells have a functional role in disease pathogenesis. MATERIALS AND METHODSVirus and mice. NSV (11) was used in this study. Stock virus was harvested from infected BHK-21 cells. Mice homozygous for a targeted disruption of the ␤2 microglobulin gene (C57BL/6J-B2m tm1Unc ) and the CD8␣ gene (C57BL/6-Cd8a tm1Mak ) and syngeneic C57BL/6J (B6) mice were pu...

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Major Histocompatibility Complex Class I Expression on Neurons in Subacute Sclerosing Panencephalitis and Experimental Subacute Measles Encephalitis

Cited by 27 publications

References 0 publications

Spread of measles virus through axonal pathways into limbic structures in the brain of TAP1 ‐/‐ mice

Spread of measles virus through axonal pathways into limbic structures in the brain of TAP1 ‐/‐ mice

Immune-Mediated Protection from Measles Virus-Induced Central Nervous System Disease Is Noncytolytic and Gamma Interferon Dependent

The Role of CD8⁺T Cells and Major Histocompatibility Complex Class I Expression in the Central Nervous System of Mice Infected with Neurovirulent Sindbis Virus

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Major Histocompatibility Complex Class I Expression on Neurons in Subacute Sclerosing Panencephalitis and Experimental Subacute Measles Encephalitis

Cited by 27 publications

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Spread of measles virus through axonal pathways into limbic structures in the brain of TAP1 ‐/‐ mice

Spread of measles virus through axonal pathways into limbic structures in the brain of TAP1 ‐/‐ mice

Immune-Mediated Protection from Measles Virus-Induced Central Nervous System Disease Is Noncytolytic and Gamma Interferon Dependent

The Role of CD8+T Cells and Major Histocompatibility Complex Class I Expression in the Central Nervous System of Mice Infected with Neurovirulent Sindbis Virus

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The Role of CD8⁺T Cells and Major Histocompatibility Complex Class I Expression in the Central Nervous System of Mice Infected with Neurovirulent Sindbis Virus