Immunoglobulins and complement in demyelination induced in mice by Theiler's virus.
Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) produces chronic demyelination and persistent infection in the central nervous system (CNS) of susceptible SJL mice. This series of experiments examined the contribution of humoral immunity and C to myelin destruction. As in multiple sclerosis, mice persistently infected with TMEV had elevated levels of IgG and oligoclonal bands in the cerebrospinal fluid (CSF). Immunoblot studies revealed that even in animals exhibiting profound demyelination, IgG in the serum and CSF was directed primarily at virus antigen rather than at normal myelin components. Inflammatory cells positive for Ig were distributed mainly around blood vessels, but occasionally they infiltrated the spinal cord parenchyma. Rare examples of myelin sheaths positive for IgG were found by immunoelectron microscopy in spinal cord sections from infected mice; the third component of complement (C3) was commonly found in the walls of CNS blood vessels but not on myelin. Neither serum nor CSF IgG from infected mice bound to myelin sheaths or other CNS components in sections of normal syngeneic spinal cord. There were significantly more demyelinating lesions in infected mice depleted of C components with cobra venom factor. These data do not support a humoral autoimmune basis for the CNS demyelination that occurs in association with persistent TMEV infection. However, the humoral immune response directed at TMEV antigens may either limit virus spread or promote virus persistence.
Rodriguez
M
M
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Lucchinetti
C F
CF
Clark
R J
RJ
Yakash
T L
TL
Markowitz
H
H
Lennon
V A
VA
D000818:Animals; D003176:Complement C3 / Q000032:analysis* / Q000172:deficiency / Q000502:physiology; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D004769:Enterovirus Infections / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis* / Q000134:cerebrospinal fluid / Q000502:physiology; D004680:Maus Elberfeld virus / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D013116:Spinal Cord / Q000276:immunology / Q000648:ultrastructure; D013997:Time Factors
D003176:Complement C3; D007074:Immunoglobulin G