TGF-beta 2 reduces demyelination, virus antigen expression, and macrophage recruitment in a viral model of multiple sclerosis.
TGF-beta 2 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-beta 2 either before or after infection with Theiler's murine encephalomyelitis virus. Treatment continued three times weekly through day 35 postinfection. TGF-beta 2 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-beta 2 had similar levels of virus-specific IgG as infected, control-treated mice. TGF-beta 2 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-beta 2. Immunostaining with an Ab to F4/80 revealed that TGF-beta 2-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-beta 2 may control virus-induced demyelination via an immunomodulatory mechanism that reduces macrophage infiltration.
Drescher
K M
KM
Departments of Neurology and Immunology, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
Murray
P D
PD
Lin
X
X
Carlino
J A
JA
Rodriguez
M
M
D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D018188:Cardiovirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D002452:Cell Count; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D009186:Myelin Sheath / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D017945:Theilovirus / Q000254:growth & development / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D010948:Viral Plaque Assay; D014779:Virus Replication
D000956:Antigens, Viral; D016212:Transforming Growth Factor beta