Preservation of motor function by inhibition of CD8+ virus peptide-specific T cells in Theiler's virus infection.

Aaron J. Johnson, J. Upshaw, K. D. Pavelko, M. Rodriguez, Larry R Pease

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58 Citations (Scopus)

Abstract

Central nervous system-infiltrating CD8+ T cells are potential mediators of neuropathology in models of multiple sclerosis induced by Theiler's murine encephalomyelitis virus (TMEV) infection. C57BL/6 mice mount a vigorous cytotoxic T lymphocyte (CTL) response against the immunodominant virus peptide VP2121-130 and clear TMEV infection. Interferon-g (IFN-g)R-/- mice also mount a strong CTL response against the VP2121-130 epitope, but because of genetic deficiencies in critical IFN-g signaling pathways, they do not clear TMEV infection and develop prominent neurological deficits within 6 wk. This pronounced disease process, coupled with a defined CTL response, provides an ideal model for evaluating the importance of antiviral CTL activity in the development of severe demyelination and loss of motor neuron function. By administering the VP2121-130 peptide before and during TMEV infection, 99% of the VP2121-130-specific CD8+ T cell response was inhibited. No decrease in virus infection was observed. Peptide treatment did result in significantly less motor dysfunction, even when no differences in levels of demyelination were observed. Although most investigators focus on the role of CD4+ T cells in demyelinating disease, these studies are the first to demonstrate a clear contribution of antiviral CD8+ T cells in neurological injury in a chronic-progressive model of multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)2760-2762
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume15
Issue number14
StatePublished - Dec 2001

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Theilovirus
Peptide T
T-cells
Virus Diseases
Viruses
Cytotoxic T-Lymphocytes
T-Lymphocytes
Demyelinating Diseases
Peptides
Interferons
Antiviral Agents
Chronic Progressive Multiple Sclerosis
Motor Neurons
Inbred C57BL Mouse
Multiple Sclerosis
Epitopes
Central Nervous System
Research Personnel
Neurology
Neurons

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "Preservation of motor function by inhibition of CD8+ virus peptide-specific T cells in Theiler's virus infection.",
abstract = "Central nervous system-infiltrating CD8+ T cells are potential mediators of neuropathology in models of multiple sclerosis induced by Theiler's murine encephalomyelitis virus (TMEV) infection. C57BL/6 mice mount a vigorous cytotoxic T lymphocyte (CTL) response against the immunodominant virus peptide VP2121-130 and clear TMEV infection. Interferon-g (IFN-g)R-/- mice also mount a strong CTL response against the VP2121-130 epitope, but because of genetic deficiencies in critical IFN-g signaling pathways, they do not clear TMEV infection and develop prominent neurological deficits within 6 wk. This pronounced disease process, coupled with a defined CTL response, provides an ideal model for evaluating the importance of antiviral CTL activity in the development of severe demyelination and loss of motor neuron function. By administering the VP2121-130 peptide before and during TMEV infection, 99{\%} of the VP2121-130-specific CD8+ T cell response was inhibited. No decrease in virus infection was observed. Peptide treatment did result in significantly less motor dysfunction, even when no differences in levels of demyelination were observed. Although most investigators focus on the role of CD4+ T cells in demyelinating disease, these studies are the first to demonstrate a clear contribution of antiviral CD8+ T cells in neurological injury in a chronic-progressive model of multiple sclerosis.",
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AU - Upshaw, J.

AU - Pavelko, K. D.

AU - Rodriguez, M.

AU - Pease, Larry R

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