TGF-β2 reduces demyelination, virus antigen expression, and macrophage recruitment in a viral model of multiple sclerosis

KM Drescher, PD Murray, X Lin, JA Carlino… - The Journal of …, 2000 - journals.aai.org
KM Drescher, PD Murray, X Lin, JA Carlino, M Rodriguez
The Journal of Immunology, 2000journals.aai.org
TGF-β2 is a potent immunoregulatory mediator that influences B cell, T cell, and
macrophage function. To test whether this cytokine alters pathology in a model of virus-
induced demyelinating disease, we treated SJL/J mice with TGF-β2 either before or after
infection with Theiler's murine encephalomyelitis virus. Treatment continued three times
weekly through day 35 postinfection. TGF-β2 administration resulted in significantly smaller
lesions and fewer virus Ag-positive cells in the spinal cords of infected SJL/J mice. Mice …
Abstract
TGF-β2 is a potent immunoregulatory mediator that influences B cell, T cell, and macrophage function. To test whether this cytokine alters pathology in a model of virus-induced demyelinating disease, we treated SJL/J mice with TGF-β2 either before or after infection with Theiler’s murine encephalomyelitis virus. Treatment continued three times weekly through day 35 postinfection. TGF-β2 administration resulted in significantly smaller lesions and fewer virus Ag-positive cells in the spinal cords of infected SJL/J mice. Mice treated with TGF-β2 had similar levels of virus-specific IgG as infected, control-treated mice. TGF-β2 administration significantly increased the level of non-virus-specific activated CTLs, but had no effect on virus-specific CTLs. TUNEL revealed a decrease in the number of apoptotic nuclei in the spinal cord white matter of mice treated in vivo with TGF-β2. Immunostaining with an Ab to F4/80 revealed that TGF-β2-treated mice had significantly fewer F4/80-positive cells in the white matter of the spinal cord as compared with infected control-treated mice. These data suggest that TGF-β2 may control virus-induced demyelination via an immunomodulatory mechanism that reduces macrophage infiltration.
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