Interpreting MHC class I expression and class I/class II reciprocity in the CNS: Reconciling divergent findings

Lampson, Lois A.

doi:10.1002/jemt.1070320402

Cited by 103 publications

(69 citation statements)

References 86 publications

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“…CNS resident cells normally express few or no MHC class I molecules (20,21,30,48). In the present study, we demonstrated that MHC class I expression was induced in the CNS after NSV infection.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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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

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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Section: Discussionmentioning

confidence: 99%

mentioning

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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“…We initially expected gene transfer of IFN-␥ to produce an immune reaction because IFN-␥ up-regulates expression of MHC class I molecules in 3LL (data not shown) and drives microglia, a putative APC of the brain, into an immune-active state (11). Our ; groups of these mice, inoculated by 3LL, were treated by either AdIFN (10 l, 2.5 ϫ 10 9 viral particles/ l; scid, n ϭ 9; beige, n ϭ 10) or AdBGAL (10 l, 2.5 ϫ 10 9 viral particles/ l; scid, n ϭ 8; beige, n ϭ 9).…”

Section: Discussionmentioning

confidence: 99%

Gene Transfer of IFN-γ into Established Brain Tumors Represses Growth by Antiangiogenesis

Fathallah‐Shaykh

Zhao

Kafrouni

et al. 2000

The Journal of Immunology

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The experiments in this paper were designed to examine the therapeutic effects of adenoviral-mediated gene transfer of IFN-γ into a mouse model of an established metastatic brain tumor. Temperature-sensitive replication-defective adenovirus was generated for gene transfer of IFN-γ (AdIFN) and β-galactosidase (AdBGAL) cDNAs in vivo. In this model, treatment with AdIFN elicits prolonged survival times and brain tumor rejection. Evidence against an immune-mediated response accounting for this result include: 1) absence of a memory immune response upon challenge, 2) lack of antitumor effects at sites distal to inoculation of AdIFN, and 3) preservation of the therapeutic effects of AdIFN in scid and beige mice and in inducible NO synthase (iNOS) knockouts. High concentrations of IFN-γ do not inhibit tumor growth in vitro making it unlikely that the antitumor effect of this treatment acts directly on the growth of the tumor cells. However, gene transfer of IFN-γ inhibits neovascularization of the tumor in a 3LL-Matrigel assay in vivo, and AdIFN induces apoptosis of endothelial cells in vivo, supporting the idea that AdIFN represses tumor growth by inhibiting angiogenesis. The substantial non-immune-mediated therapeutic benefits of AdIFN in animals paves the way for devising novel strategies for treating human brain tumors.

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“…[1][2][3][4][5][6][7] Identifying which cell types express MHC, and therefore which cells can directly interact with and be damaged by T cells, is crucial to understanding the pathogenesis of neurological diseases involving inflammation in animal models and in humans.…”

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confidence: 99%

In Vivo Expression of Major Histocompatibility Complex Molecules on Oligodendrocytes and Neurons during Viral Infection

Redwine

Buchmeier

Evans

2001

The American Journal of Pathology

106

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Demyelination in multiple sclerosis and in animal models is associated with infiltrating CD8؉ and CD4؉ T cells. Although oligodendrocytes and axons are damaged in these diseases, the roles T cells play in the demyelination process are not completely understood. Antigen-specific CD8؉ T cell lysis of target cells is dependent on interactions between the T cell receptor and major histocompatibility complex (MHC) class I-peptide complexes on the target cell. In the normal central nervous system, expression of MHC molecules is very low but often increases during inflammation. We set out to precisely define which central nervous system cells express MHC molecules in vivo during infection with a strain of murine hepatitis virus that causes a chronic, inflammatory demyelinating disease. Using double immunofluorescence labeling, we show that during acute infection with murine hepatitis virus, MHC class I is expressed in vivo by oligodendrocytes, neurons, microglia, and endothelia, and MHC class II is expressed only by microglia. These data indicate that oligodendrocytes and neurons have the potential to present antigen to T cells and thus be damaged by direct antigen-specific interactions with CD8؉ T lymphocytes. Cell death associated with a local inflammatory response within the central nervous system (CNS) occurs in many neurological diseases, including multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML) caused by JC virus.

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Interpreting MHC class I expression and class I/class II reciprocity in the CNS: Reconciling divergent findings

Cited by 103 publications

References 86 publications

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

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

Gene Transfer of IFN-γ into Established Brain Tumors Represses Growth by Antiangiogenesis

In Vivo Expression of Major Histocompatibility Complex Molecules on Oligodendrocytes and Neurons during Viral Infection

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Interpreting MHC class I expression and class I/class II reciprocity in the CNS: Reconciling divergent findings

Cited by 103 publications

References 86 publications

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

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

Gene Transfer of IFN-γ into Established Brain Tumors Represses Growth by Antiangiogenesis

In Vivo Expression of Major Histocompatibility Complex Molecules on Oligodendrocytes and Neurons during Viral Infection

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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

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