4.6 Article

Central nervous system pathology caused by autoreactive CD8+ T-cell clones following virus infection

Journal

JOURNAL OF VIROLOGY
Volume 79, Issue 23, Pages 14640-14646

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.79.23.14640-14646.2005

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Funding

  1. NINDS NIH HHS [R01 NS034497, 5R01 NS 34497] Funding Source: Medline

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Theiler's murine encephalomyelitis virus (TMEV) causes a demyelinating disease in infected mice which has similarities to multiple sclerosis. Spleen cells from TMEV-infected SJL/J mice stimulated with antigen-presenting cells infected with TMEV resulted in a population of autoreactive CD8(+) cytotoxic T cells that kill uninfected syngeneic cells. We established CD8(+) T cell clones that could kill both TMEV-infected and uninfected syngeneic targets, although infected target cells were killed more efficiently. The CD8(+) T-cell clones produced gamma interferon when incubated with either infected or uninfected syngeneic target cells. Intracerebral injection of the clones into naive mice induced degeneration, not only in the brain, but also in the spinal cord. This suggests that CD8(+) Tcl cells could play a pathogenic role in central nervous system inflammation.

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