Abstract
Acute viral encephalitis requires rapid pathogen elimination without significant bystander tissue damage. In this article, we show that IL-10, a potent anti-inflammatory cytokine, is produced transiently at the peak of infection by CD8 T cells in the brains of coronavirus-infected mice. IL-10(+)CD8 and IL-10(-)CD8 T cells interconvert during acute disease, possibly based on recent Ag exposure. Strikingly, IL-10(+)CD8 T cells were more highly activated and cytolytic than IL-10(-)CD8 T cells, expressing greater levels of proinflammatory cytokines and chemokines, as well as cytotoxic proteins. Even though these cells are highly proinflammatory, IL-10 expressed by these cells was functional. Furthermore, IL-10 produced by CD8 T cells diminished disease severity in mice with coronavirus-induced acute encephalitis, suggesting a self-regulatory mechanism that minimizes immunopathological changes.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Cell Line, Tumor
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Cells, Cultured
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Coronaviridae Infections / immunology
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Coronaviridae Infections / metabolism
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Coronaviridae Infections / prevention & control
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Cytotoxicity, Immunologic*
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Encephalomyelitis, Acute Disseminated / immunology*
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Encephalomyelitis, Acute Disseminated / pathology
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Encephalomyelitis, Acute Disseminated / prevention & control
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Inflammation Mediators / metabolism
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Interleukin-10 / biosynthesis*
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Interleukin-10 / deficiency
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Interleukin-10 / physiology
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Lymphocyte Activation / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Murine hepatitis virus / immunology
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism*
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T-Lymphocytes, Cytotoxic / transplantation
Substances
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IL10 protein, mouse
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Inflammation Mediators
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Interleukin-10